Sildenafil

Identification

Summary

Sildenafil is a phosphodiesterase inhibitor used for the treatment of erectile dysfunction.

Brand Names
Liqrev, Revatio, Viagra, Vizarsin
Generic Name
Sildenafil
DrugBank Accession Number
DB00203
Background

In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) 11,12,13,14,15,16,8,9. The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid 11,12,13,14,15,16,8,9.

Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment for angina - or chest pain associated with inadequate blood flow to the heart - before being serendipitously indicated for treating erectile dysfunction in the late 1980s 7. Nevertheless, it is because of this mechanism that sildenafil is also indicated for treating pulmonary arterial hypertension but is also additionally notorious for interacting with various anti-anginal or anti-hypertensive agents to develop potentially rapid, excessive, and/or fatal hypotensive crises 4,5,6.

Regardless, sildenafil, among a variety of other similar or related PDE5 inhibitors, has become a common and effective treatment for erectile dysfunction and since its formal approval for medical use in the public in 1998 7, continues to see millions of prescriptions written for it internationally. Although the medication has historically been most popularly recognized as Pfizer's brand name Viagra, sildenafil is currently available generically and even as a non-prescription over the counter medication in some countries 10.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 474.576
Monoisotopic: 474.204924168
Chemical Formula
C22H30N6O4S
Synonyms
  • 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine
  • Sildenafil
  • Sildenafilo
External IDs
  • HIP-0908
  • HIP0908

Pharmacology

Indication

Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications:

(1) the treatment of erectile dysfunction 5,8,12,13,16; and

(2) treatment of pulmonary hypertension, where: a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening 11. The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy 11. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) 11;

b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy 14. In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy 14; and

c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity 15. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease 15. The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension 15. Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease 15.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatErectile dysfunctionCombination Product in combination with: Dapoxetine (DB04884)••••••••••••••••••
Management ofErectile dysfunction••••••••••••
Management ofNyha functional class ii-iii pulmonary arterial hypertension••••••••••••
Used in combination to treatPremature ejaculationCombination Product in combination with: Dapoxetine (DB04884)••••••••••••••••••
Treatment ofPulmonary arterial hypertension (pah)•••••••••••••••••••••• ••••••••••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5) 11,12,13,14,15,16,8,9. Its effect is more potent on PDE5 than on other known phosphodiesterases 11,12,13,14,15,16,8,9. In particular, there is a 10-times selectivity over PDE6 which is involved in the phototransduction pathway in the retina 11,12,13,14,15,16,8,9. There is an 80-times selectivity over PDE1, and over 700-times over PDE 2, 3, 4, 7, 8, 9, 10 and 11 11,12,13,14,15,16,8,9. And finally, sildenafil has greater than 4,000-times selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility 11,12,13,14,15,16,8,9.

In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (via the use of RigiScan®), after sildenafil administration compared with placebo 11,12,13,14,15,16,8,9. Most studies assessed the efficacy of sildenafil approximately 60 minutes post-dose 11,12,13,14,15,16,8,9. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration 11,12,13,14,15,16,8,9. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours 11,12,13,14,15,16,8,9.

Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects 11,12,13,14,15,16,8,9. After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively 11,12,13,14,15,16,8,9. After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg)11,12,13,14,15,16,8,9 . At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen 11,12,13,14,15,16,8,9.

Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG 11,12,13,14,15,16,8,9. After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either 11,12,13,14,15,16,8,9.

In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline 11,12,13,14,15,16,8,9. Mean pulmonary systolic blood pressure decreased by 9% 11,12,13,14,15,16,8,9. Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries 11,12,13,14,15,16,8,9.

Mild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose 11,12,13,14,15,16,8,9. The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina 11,12,13,14,15,16,8,9. Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test) 11,12,13,14,15,16,8,9.

Mechanism of action

Sildenafil is an oral therapy for erectile dysfunction 5,12,13,16,8. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis 5,12,13,16,8.

The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation 5,12,13,16,8. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood 5,12,13,16,8.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP 5,12,13,16,8. Sildenafil has a peripheral site of action on erections 5,12,13,16,8. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue 5,12,13,16,8. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP 5,12,13,16,8. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects 5,12,13,16,8.

Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature 4,11,14,15,9. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation 4,11,14,15,9. In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation 4,11,14,15,9.

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Humans
NRetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
Humans
NRetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
Humans
UOrnithine decarboxylase
downregulator
Humans
UProgrammed cell death 1 ligand 1
downregulator
Humans
Absorption

Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes) of oral administration in a fasting patient 11,12,13,14,15,16,8,9. Moreover, the mean absolute bioavailability observed for sildenafil is about 41% (from a range of 25-63%) 11,12,13,14,15,16,8,9. In particular, after oral three times a day dosing of sildenafil, the AUC and Cmax increase in proportion with dose over the recommended dosage range of 25-100 mg 11,12,13,14,15,16,8,9.

When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses 11,12,13,14,15,16,8,9.

Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% 11,12,13,14,15,16,8,9. Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % 11,12,13,14,15,16,8,9.

Volume of distribution

The mean steady-state volume of distribution documented for sildenafil is approximately 105 L - a value which suggests the medication undergoes distribution into the tissues 11,12,13,14,15,16,8,9.

Protein binding

It is generally observed that sildenafil and its main circulating N-desmethyl metabolite are both estimated to be about 96% bound to plasma proteins 11,12,13,14,15,16,8,9. Nevertheless, it has been determined that protein binding for sildenafil is independent of total drug concentrations 11,12,13,14,15,16,8,9.

Metabolism

The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic isoenzymes 6,11,12,13,14,15,16,8,9. The predominant circulating metabolite results from the N-demethylation of sildenafil 6,11,12,13,14,15,16,8,9. This particular resultant metabolite possesses a phosphodiesterase selectivity that is similar to the parent sildenafil molecule and a corresponding in vitro potency for PDE5 that is approximately 50% that of the parent drug 6,11,12,13,14,15,16,8,9. Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects 6,11,12,13,14,15,16,8,9. This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours 6,11,12,13,14,15,16,8,9.

In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects 6,11,12,13,14,15,16,8,9.

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Route of elimination

After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose) 11,12,13,14,15,16,8,9.

Half-life

The terminal phase half-life observed for sildenafil is approximately 3 to 5 hours 11,12,13,14,15,16,8,9.

Clearance

The total body clearance documented for sildenafil is 41 L/h 11,12,13,14,15,16,8,9.

Adverse Effects
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Toxicity

In single-dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased 11,12,13,14,15,16,8,9. Doses of 200 mg did not result in increased efficacy but the incidence of adverse reaction (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased 11,12,13,14,15,16,8,9.

Due to the lack of data on the effect of sildenafil indicated for the treatment of pulmonary arterial hypertension (PAH) in pregnant women, sildenafil is not recommended for women of childbearing potential unless also using appropriate contraceptive measures 11,14,15,9.

The safety and efficacy of sildenafil indicated for treating PAH in a woman during labor and delivery have not been studied 11,14,15,9. Caution should ultimately be exercised when sildenafil is administered to nursing women as it is not known if sildenafil or its metabolites are excreted in human breast milk 11,14,15,9.

The safety and efficacy of sildenafil for the treatment of PAH in children below 1 year of age has not been established as no data is available 15.

Clinical experience with the elderly population in the use of sildenafil for the treatment of PAH has been varied. Some reports suggest that there are no identified differences in responses between elderly and younger patients 11 while others have documented that clinical efficacy as measured by 6-minute walk distance could be less in elderly patients 9. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy 11.

Conversely, when sildenafil was used to treat erectile dysfunction in healthy elderly volunteers (65 years or over), a reduced clearance of sildenafil was observed 12,8. This reduction resulted in about 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years) 12,8. Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40% 12,8.

Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg 11,12,13,14,15,16,8,9. Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis 11,12,13,14,15,16,8,9.

Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity 11,12,13,14,15,16,8,9.

There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC 11,12,13,14,15,16,8,9.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Angiotensin-converting enzyme---Not AvailableAlu insertions / Alu insertions  … show all Effect Directly StudiedPatients with this genotype have increased frequency of positive erectile response when using sildenafil to treat erectile dysfunctionDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3---(T;T)T allele, homozygoteEffect Directly StudiedPatients with this genotype have increased frequency of positive erectile response when using sildenafil to treat erectile dysfunctionDetails

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe risk or severity of hypotension can be increased when Sildenafil is combined with Abaloparatide.
AbametapirThe serum concentration of Sildenafil can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Sildenafil can be increased when combined with Abatacept.
AbciximabThe risk or severity of hemorrhage can be increased when Abciximab is combined with Sildenafil.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Sildenafil.
Food Interactions
  • Take with or without food. If taken with a high-fat meal the medicine may take a little longer to start working.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Sildenafil citrateBW9B0ZE037171599-83-0DEIYFTQMQPDXOT-UHFFFAOYSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act SildenafilTablet50 mgOralActavis Pharma Company2012-11-082018-06-26Canada flag
Act SildenafilTablet25 mgOralActavis Pharma Company2012-11-082018-06-26Canada flag
Act SildenafilTablet100 mgOralActavis Pharma Company2012-11-082018-06-26Canada flag
GranpidamTablet, film coated20 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
GranpidamTablet, film coated20 mgOralAccord Healthcare S.L.U.2021-01-12Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-sildenafilTablet100 mgOralAccel Pharma Inc2019-08-15Not applicableCanada flag
Accel-sildenafilTablet50 mgOralAccel Pharma Inc2019-08-15Not applicableCanada flag
Accel-sildenafilTablet25 mgOralAccel Pharma Inc2019-08-15Not applicableCanada flag
Ag-sildenafilTablet100 mgOralAngita Pharma Inc.2018-12-212022-11-15Canada flag
Ag-sildenafilTablet50 mgOralAngita Pharma Inc.2018-12-212022-11-15Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DAPOKSEL 30 MG/50 MG FILM TABLET ,3 FILM TABLETSildenafil citrate (50 mg) + Dapoxetine hydrochloride (30 mg)Tablet, film coatedOralNOBEL İLAÇ SAN. VE TİC. A.Ş.2016-05-242017-11-14Turkey flag
DAPOKSEL 30 MG/50 MG FILM TABLET ,6 FILM TABLETSildenafil citrate (50 mg) + Dapoxetine hydrochloride (30 mg)Tablet, film coatedOralNOBEL İLAÇ SAN. VE TİC. A.Ş.2016-05-242017-11-14Turkey flag
DAPOXIL 30/50 MG FILM KAPLI TABLET, 3 FILM KAPLI TABLETSildenafil citrate (50 mg) + Dapoxetine hydrochloride (30 mg)Tablet, coatedOralVİTALİS İLAÇ SAN. TİC. A.Ş.2020-08-142021-02-15Turkey flag
DAPOXIL 30/50 MG FILM KAPLI TABLET, 6 FILM KAPLI TABLETSildenafil citrate (50 mg) + Dapoxetine hydrochloride (30 mg)Tablet, coatedOralVİTALİS İLAÇ SAN. TİC. A.Ş.2020-08-142021-02-15Turkey flag
DAPOXIL 30/50 MG FILM KAPLI TABLET,18 FILM KAPLI TABLETSildenafil citrate (50 mg) + Dapoxetine hydrochloride (30 mg)Tablet, coatedOralVİTALİS İLAÇ SAN. TİC. A.Ş.2020-08-142021-02-15Turkey flag

Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesG04BE03 — Sildenafil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Pyrazolopyrimidines / Benzenesulfonyl compounds / Phenoxy compounds / Phenol ethers / Pyrimidones / Alkyl aryl ethers / N-methylpiperazines / Organosulfonamides / Sulfonyls / Pyrazoles
show 7 more
Substituents
1,4-diazinane / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenesulfonamide / Benzenesulfonyl group / Ether / Heteroaromatic compound
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, piperazines, pyrazolopyrimidine (CHEBI:9139)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3M7OB98Y7H
CAS number
139755-83-2
InChI Key
BNRNXUUZRGQAQC-UHFFFAOYSA-N
InChI
InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)
IUPAC Name
5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one
SMILES
CCCC1=NN(C)C2=C1N=C(NC2=O)C1=CC(=CC=C1OCC)S(=O)(=O)N1CCN(C)CC1

References

Synthesis Reference

Peter James Dunn, Albert Shaw Wood, "Process for preparing sildenafil." U.S. Patent US5955611, issued December, 1994.

US5955611
General References
  1. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C: Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47-52. [Article]
  2. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM: ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Jan;33(1):273-82. [Article]
  3. Fries R, Shariat K, von Wilmowsky H, Bohm M: Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005 Nov 8;112(19):2980-5. [Article]
  4. Unegbu C, Noje C, Coulson JD, Segal JB, Romer L: Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors. Pediatrics. 2017 Mar;139(3). pii: peds.2016-1450. doi: 10.1542/peds.2016-1450. [Article]
  5. Gong B, Ma M, Xie W, Yang X, Huang Y, Sun T, Luo Y, Huang J: Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2017 Oct;49(10):1731-1740. doi: 10.1007/s11255-017-1644-5. Epub 2017 Jul 24. [Article]
  6. Nichols DJ, Muirhead GJ, Harness JA: Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53 Suppl 1:5S-12S. [Article]
  7. Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ: The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction. Sex Med Rev. 2019 Jan;7(1):115-128. doi: 10.1016/j.sxmr.2018.06.005. Epub 2018 Oct 6. [Article]
  8. Electronic Medicines Compendium: Sildenafil 25mg, 50mg, 100mg film-coated tablets Monograph [Link]
  9. Electronic Medicines Compendium: Revatio (sildenafil citrate) 20 mg film-coated tablets Monograph [Link]
  10. Forbes: With Viagra Now Available Over-The-Counter In The U.K., Will The U.S. Follow Suit? [Link]
  11. Revatio (sildenafil) FDA Label [File]
  12. Viagra (sildenafil citrate) FDA Label [File]
  13. Viagra (sildenafil citrate) Tablets 25 mg, 50 mg, and 100 mg Canadian Product Monograph [File]
  14. Revatio (sildenafil citrate) Canadian Product Monograph [File]
  15. Revatio (sildenafil citrate) EMA Label [File]
  16. Viagra (sildenafil citrate) EMA Label [File]
Human Metabolome Database
HMDB0005039
KEGG Drug
D08514
KEGG Compound
C07259
PubChem Compound
5212
PubChem Substance
46508371
ChemSpider
5023
BindingDB
50238854
RxNav
136411
ChEBI
9139
ChEMBL
CHEMBL192
ZINC
ZINC000019796168
Therapeutic Targets Database
DAP000614
PharmGKB
PA451346
PDBe Ligand
VIA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Sildenafil
PDB Entries
1tbf / 1udt / 1xos / 2h42 / 3jwq
FDA label
Download (80.5 KB)
MSDS
Download (37.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableSexual impotency1
4CompletedBasic ScienceEmphysema1
4CompletedBasic ScienceSyndrome, Metabolic1
4CompletedDiagnosticLeft Ventricular Dysfunction / Pulmonary Arterial Hypertension (PAH)1
4CompletedEducational/Counseling/TrainingBlindness1

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Pfizer ireland pharmaceuticals
Packagers
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Cardinal Health
  • Direct Dispensing Inc.
  • Diversified Healthcare Services Inc.
  • Gallipot
  • MSN Laboratories Ltd.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • US Pharmaceutical Group
Dosage Forms
FormRouteStrength
Tablet, chewableOral25 MG
Tablet, film coatedOral140.5 MG
TabletOral25 mg
TabletOral50.000 mg
TabletOral140.48 mg
SuspensionOral25 MG/ML
Injection, suspension
Tablet, chewableOral5000000 mg
Tablet, film coatedOral140480 Mg
Tablet, film coatedOral70240 Mg
Tablet, film coatedOral
Tablet, film coatedOral
Tablet, coatedOral
Tablet, delayed releaseOral35.112 mg
CapsuleOral50.00 mg
Tablet, film coatedOral70.225 mg
Film, solubleOral70241 Mg
TabletOral100 mg
TabletOral50 mg
Capsule, liquid filledOral25 mg
Capsule, liquid filledOral50 mg
Tablet, solubleOral50 mg
TabletOral70.240 mg
Tablet, film coatedOral20 MG
SolutionIntravenous10 mg
TabletOral100.0 mg
TabletOral25.0 mg
TabletOral50.0 mg
SolutionOral0.01838 g
TabletOral140.450 mg
TabletOral70.225 mg
SuspensionOral10 mg/1mL
SolutionOral1.838 g
FilmBuccal70.240 mg
TabletOral140.480 mg
Tablet, film coatedOral70.24 mg
TabletOral50.00 mg
GelOral28.100 mg
TabletOral140.400 mg
TabletOral100.000 mg
Film, solubleOral100 mg
Film, solubleOral25 MG
Film, solubleOral75 MG
TabletOral28.090 mg
Injection, solutionIntravenous0.8 mg/1mL
Injection, solutionIntravenous0.8 MG/ML
Powder, for suspensionOral10 MG/ML
SolutionIntravenous0.8 mg / mL
Syrup
TabletOral20 mg
Tablet, coatedOral20 mg
Tablet, film coatedOral20.0 mg/unit
TabletOral
SuspensionOral25.000 mg
Film, solubleOral70.23 MG
Tablet, film coatedOral100.0 mg
Tablet, film coatedOral50.0 mg
CapsuleOral25 mg
CapsuleOral50 mg
Tablet, film coatedOral25 mg
For suspensionOral10 mg/1mL
Injection, solutionIntravenous10 mg/12.5mL
TabletOral100 mg/1
TabletOral20 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral20 mg/1
Tablet, chewableBuccal50 mg
Tablet, chewableOral50 mg
Tablet, coatedOral5000000 mg
Tablet, coatedOral70.24 mg
Tablet, coatedOral50 mg
Tablet, chewableOral100 MG
Powder, for suspensionOral10 mg/1mL
Tablet, chewableOral
Tablet, coatedOral2500000 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral50 mg
FilmOral50 mg
Film, solubleOral50 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, orally disintegratingOral50 mg
Tablet, coatedOral100 mg
Tablet, coatedOral25 mg
Film, solubleOral
Tablet, orally disintegratingOral100 mg
Tablet, orally disintegratingOral25 mg
TabletOral70.241 mg
Tablet, film coatedOral140.48 MG
FilmBuccal70.230 mg
Prices
Unit descriptionCostUnit
Sildenafil citrate powder24.38USD g
Viagra 50 mg tablet19.45USD tablet
Viagra 100 mg tablet19.45USD tablet
Viagra 25 mg tablet19.45USD tablet
Revatio 20 mg tablet17.5USD tablet
Revatio 10 mg/12.5 ml vial9.33USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5250534No1993-10-052012-03-27US flag
CA2324324No2005-12-202020-10-26Canada flag
CA2044748No1998-02-032011-06-17Canada flag
US6469012Yes2002-10-222020-04-22US flag
US11337979No2018-12-242038-12-24US flag
US11464778No2018-12-242038-12-24US flag
US11759468No2018-12-242038-12-24US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189-190 °CNot Available
water solubility3.5 mg/mLNot Available
logP1.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.46 mg/mLALOGPS
logP1.8ALOGPS
logP1.87Chemaxon
logS-3ALOGPS
pKa (Strongest Acidic)11.14Chemaxon
pKa (Strongest Basic)5.99Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area109.13 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity139.44 m3·mol-1Chemaxon
Polarizability51.18 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6461
Caco-2 permeable+0.7078
P-glycoprotein substrateSubstrate0.7753
P-glycoprotein inhibitor IInhibitor0.672
P-glycoprotein inhibitor IIInhibitor0.8877
Renal organic cation transporterNon-inhibitor0.648
CYP450 2C9 substrateNon-substrate0.6553
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7254
CYP450 1A2 substrateNon-inhibitor0.823
CYP450 2C9 inhibitorInhibitor0.6864
CYP450 2D6 inhibitorNon-inhibitor0.8394
CYP450 2C19 inhibitorNon-inhibitor0.8222
CYP450 3A4 inhibitorInhibitor0.849
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5839
Ames testNon AMES toxic0.5683
CarcinogenicityNon-carcinogens0.6658
BiodegradationNot ready biodegradable0.7641
Rat acute toxicity2.6730 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8664
hERG inhibition (predictor II)Inhibitor0.7602
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-006t-9004300000-55c87eff7b6ad40ea3d5
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0059-2494500000-e3f8387aee5a0463363c
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-05s0-3892000000-aa19715309275e16a6c0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0059-2494500000-e3f8387aee5a0463363c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-05s0-3892000000-aa19715309275e16a6c0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0001900000-77fcc940621f3df9617b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0000900000-ef34b5271da197193eb1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0000900000-51cf0b8d94160875f06f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00r2-0001900000-6c86d10055edeb37fa34
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-7800900000-69fdda5ec4e95d6d367a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01t9-2010900000-647487ea81f1fab90361
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-233.2005827
predicted
DarkChem Lite v0.1.0
[M-H]-237.5357827
predicted
DarkChem Lite v0.1.0
[M-H]-208.75966
predicted
DeepCCS 1.0 (2019)
[M+H]+233.9926827
predicted
DarkChem Lite v0.1.0
[M+H]+238.7927827
predicted
DarkChem Lite v0.1.0
[M+H]+211.15523
predicted
DeepCCS 1.0 (2019)
[M+Na]+232.9520827
predicted
DarkChem Lite v0.1.0
[M+Na]+238.0477827
predicted
DarkChem Lite v0.1.0
[M+Na]+217.06773
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da
References
  1. Carson CC: Long-term use of sildenafil. Expert Opin Pharmacother. 2003 Mar;4(3):397-405. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  3. Corbin JD, Francis SH, Webb DJ: Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology. 2002 Sep;60(2 Suppl 2):4-11. [Article]
  4. Kruuse C, Thomsen LL, Birk S, Olesen J: Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 2003 Jan;126(Pt 1):241-7. [Article]
  5. Rybalkin SD, Rybalkina IG, Shimizu-Albergine M, Tang XB, Beavo JA: PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J. 2003 Feb 3;22(3):469-78. [Article]
  6. Wang H, Liu Y, Huai Q, Cai J, Zoraghi R, Francis SH, Corbin JD, Robinson H, Xin Z, Lin G, Ke H: Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. J Biol Chem. 2006 Jul 28;281(30):21469-79. Epub 2006 May 30. [Article]
  7. Wang H, Ye M, Robinson H, Francis SH, Ke H: Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. [Article]
  8. Wang J, Re J, Wang Z: [Mode of action of sildenafil]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1999 Dec;21(6):493-6. [Article]
  9. Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6G
Uniprot ID
P18545
Uniprot Name
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9643.09 Da
References
  1. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG: Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol. 2006 Dec;50(6):1194-207; discussion 1207. Epub 2006 Jun 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6H
Uniprot ID
Q13956
Uniprot Name
Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9074.36 Da
References
  1. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG: Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol. 2006 Dec;50(6):1194-207; discussion 1207. Epub 2006 Jun 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
General Function
Protein homodimerization activity
Specific Function
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
Gene Name
ODC1
Uniprot ID
P11926
Uniprot Name
Ornithine decarboxylase
Molecular Weight
51147.73 Da
References
  1. Booth L, Roberts JL, Poklepovic A, Dent P: [pemetrexed + sildenafil], via autophagy-dependent HDAC downregulation, enhances the immunotherapy response of NSCLC cells. Cancer Biol Ther. 2017 Sep 2;18(9):705-714. doi: 10.1080/15384047.2017.1362511. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
General Function
Not Available
Specific Function
Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell ...
Gene Name
CD274
Uniprot ID
Q9NZQ7
Uniprot Name
Programmed cell death 1 ligand 1
Molecular Weight
33275.095 Da
References
  1. Booth L, Roberts JL, Poklepovic A, Dent P: [pemetrexed + sildenafil], via autophagy-dependent HDAC downregulation, enhances the immunotherapy response of NSCLC cells. Cancer Biol Ther. 2017 Sep 2;18(9):705-714. doi: 10.1080/15384047.2017.1362511. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [Article]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  3. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. doi: 10.1046/j.1365-2125.2001.00318.x. [Article]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [Article]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. doi: 10.1046/j.1365-2125.2001.00318.x. [Article]
  3. Sildenafil FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Warrington JS, Shader RI, von Moltke LL, Greenblatt DJ: In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos. 2000 Apr;28(4):392-7. [Article]
  2. Hyland R, Roe EG, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. doi: 10.1046/j.1365-2125.2001.00318.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Warrington JS, Shader RI, von Moltke LL, Greenblatt DJ: In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos. 2000 Apr;28(4):392-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Sheweita SA, Wally M, Hassan M: Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats. Oxid Med Cell Longev. 2016;2016:4970906. doi: 10.1155/2016/4970906. Epub 2016 Oct 9. [Article]
  2. List of drugs that may have potential CYP2E1 interactions [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [Article]
  2. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name
ABCC5
Uniprot ID
O15440
Uniprot Name
Multidrug resistance-associated protein 5
Molecular Weight
160658.8 Da
References
  1. Jedlitschky G, Burchell B, Keppler D: The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem. 2000 Sep 29;275(39):30069-74. [Article]
  2. Reid G, Wielinga P, Zelcer N, De Haas M, Van Deemter L, Wijnholds J, Balzarini J, Borst P: Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol. 2003 May;63(5):1094-103. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Kalliokoski A, Niemi M: Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x. Epub 2009 Sep 25. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Shi Z, Tiwari AK, Shukla S, Robey RW, Singh S, Kim IW, Bates SE, Peng X, Abraham I, Ambudkar SV, Talele TT, Fu LW, Chen ZS: Sildenafil reverses ABCB1- and ABCG2-mediated chemotherapeutic drug resistance. Cancer Res. 2011 Apr 15;71(8):3029-41. doi: 10.1158/0008-5472.CAN-10-3820. Epub 2011 Mar 14. [Article]
  2. Higashi H, Watanabe N, Tamura R, Taguchi M: In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319. doi: 10.1248/bpb.b17-00278. [Article]
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Drug created at June 13, 2005 13:24 / Updated at March 19, 2024 11:06