Gramicidin D

Identification

Summary

Gramicidin D is a bactericidal antibiotic used in the treatment of dermatological and ophthalmic infections.

Brand Names

Sofracort, Soframycin, Triple Antibiotic, Viaderm Kc

Generic Name

Gramicidin D

DrugBank Accession Number

DB00027

Background

Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids, which assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. Active against most Gram-positive bacteria and some Gram-negative organisms, Gramicidin D is used primarily as a topical antibiotic and is also found in Polysporin ophthalmic solution.

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 1811.253
Monoisotopic: 1810.033419343
Chemical Formula: C₉₆H₁₃₅N₁₉O₁₆

Synonyms

Bacillus brevis gramicidin D
Gramicidin
Gramicidin A
Gramicidin B
Gramicidin C
Gramicidina
Gramicidine

Pharmacology

Indication

For treatment of skin lesions, surface wounds and eye infections.

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution.

Mechanism of action

Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization (it acts as a channel). This leads to (i) loss of intracellular solutes (e.g., K+ and amino acids); (ii) dissipation of the transmembrane potential; (iii) inhibition of respiration; (iv) a reduction in ATP pools; and (v) inhibition of DNA, RNA, and protein synthesis, which leads to cell death.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

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.

Drug	Interaction
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Acenocoumarol	The risk or severity of bleeding can be increased when Gramicidin D is combined with Acenocoumarol.
BCG vaccine	The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Gramicidin D.
Dicoumarol	The risk or severity of bleeding can be increased when Gramicidin D is combined with Dicoumarol.
Estetrol	The therapeutic efficacy of Estetrol can be decreased when used in combination with Gramicidin D.
Fluindione	The risk or severity of bleeding can be increased when Gramicidin D is combined with Fluindione.
Phenindione	The risk or severity of bleeding can be increased when Gramicidin D is combined with Phenindione.
Phenprocoumon	The risk or severity of bleeding can be increased when Gramicidin D is combined with Phenprocoumon.
Vibrio cholerae CVD 103-HgR strain live antigen	The therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Gramicidin D.
Warfarin	The risk or severity of bleeding can be increased when Gramicidin D is combined with Warfarin.

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Food Interactions

No interactions found.

Products

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International/Other Brands

Sofradex (Sanofi)

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Antibiotic Cream	Gramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Technilab Pharma Inc.	1998-11-03	2005-08-05
Antibiotic Cream	Gramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Cellchem Pharmaceuticals Inc.	2009-12-23	Not applicable
Antibiotic Cream	Gramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Canadian Custom Packaging Company	2012-03-22	2020-09-11
Antibiotic Cream for Kids	Gramicidin D (0.25 mg / g) + Lidocaine hydrochloride (50 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Cellchem Pharmaceuticals Inc.	Not applicable	Not applicable
Antibiotic Cream for Kids	Gramicidin D (0.25 mg / g) + Lidocaine hydrochloride (50 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Taro Pharmaceuticals, Inc.	2009-07-30	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg / g) + Lidocaine hydrochloride (50 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Cellchem Pharmaceuticals Inc.	2009-12-23	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg / g) + Lidocaine hydrochloride (40 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Canadian Custom Packaging Company	2012-04-09	2020-09-12
Antibiotic Cream Plus Pain Relief for Kids	Gramicidin D (0.25 mg / g) + Lidocaine hydrochloride (40 mg / g) + Polymyxin B sulfate (10000 unit / g)	Cream	Topical	Canadian Custom Packaging Company	2012-07-11	2020-06-06
Antibiotic Drops	Gramicidin D (0.025 mg / mL) + Polymyxin B sulfate (10000 unit / mL)	Solution	Auricular (otic); Ophthalmic	Sandoz Canada Incorporated	2017-06-01	2021-05-27
Antibiotic Ear Drops	Gramicidin D (0.025 mg / mL) + Polymyxin B sulfate (10000 unit / mL)	Solution / drops	Auricular (otic)	Sandoz Canada Incorporated	2017-09-01	2021-06-09

Chemical Identifiers

UNII: 5IE62321P4
CAS number: 1405-97-6
InChI Key: NDAYQJDHGXTBJL-MWWSRJDJSA-N
InChI: InChI=1S/C96H135N19O16/c1-50(2)36-71(105-79(118)48-102-93(128)80(54(9)10)103-49-117)86(121)104-58(17)84(119)113-82(56(13)14)95(130)115-83(57(15)16)96(131)114-81(55(11)12)94(129)112-78(43-62-47-101-70-33-25-21-29-66(62)70)92(127)108-74(39-53(7)8)89(124)111-77(42-61-46-100-69-32-24-20-28-65(61)69)91(126)107-73(38-52(5)6)88(123)110-76(41-60-45-99-68-31-23-19-27-64(60)68)90(125)106-72(37-51(3)4)87(122)109-75(85(120)97-34-35-116)40-59-44-98-67-30-22-18-26-63(59)67/h18-33,44-47,49-58,71-78,80-83,98-101,116H,34-43,48H2,1-17H3,(H,97,120)(H,102,128)(H,103,117)(H,104,121)(H,105,118)(H,106,125)(H,107,126)(H,108,127)(H,109,122)(H,110,123)(H,111,124)(H,112,129)(H,113,119)(H,114,131)(H,115,130)/t58-,71+,72+,73+,74+,75-,76-,77-,78-,80-,81+,82+,83-/m0/s1
IUPAC Name: (2R)-N-[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-[(2-hydroxyethyl)carbamoyl]-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]-2-{2-[(2S)-2-formamido-3-methylbutanamido]acetamido}-4-methylpentanamide
SMILES: CC(C)C[C@@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCCO

References

Synthesis Reference

U.S.Patent 2,534,541.

General References

Ketchem RR, Lee KC, Huo S, Cross TA: Macromolecular structural elucidation with solid-state NMR-derived orientational constraints. J Biomol NMR. 1996 Jul;8(1):1-14. [Article]
Townsley LE, Tucker WA, Sham S, Hinton JF: Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry. 2001 Oct 2;40(39):11676-86. [Article]
Burkhart BM, Gassman RM, Langs DA, Pangborn WA, Duax WL, Pletnev V: Gramicidin D conformation, dynamics and membrane ion transport. Biopolymers. 1999;51(2):129-44. [Article]

External Links

KEGG Drug: D04369
PubChem Compound: 45267103
PubChem Substance: 46507412
ChemSpider: 24623445
RxNav: 5011
ChEMBL: CHEMBL557217
Therapeutic Targets Database: DAP001327
PharmGKB: PA449808
Wikipedia: Gramicidin

MSDS

Download (71.9 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Unknown Status	Treatment	Hordeolum	1
Not Available	Withdrawn	Prevention	Bloodstream Infections (BSI) / Skin Diseases, Infectious	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Johnson & Johnson Healthcare
Monarch Pharmacy
Professional Co.

Dosage Forms

Form	Route	Strength
Solution	Auricular (otic); Ophthalmic
Solution / drops	Auricular (otic)
Solution / drops	Ophthalmic
Solution	Ophthalmic
Liquid	Auricular (otic); Ophthalmic
Ointment	Ophthalmic
Solution / drops	Auricular (otic); Ophthalmic
Solution / drops	Topical
Ointment	Auricular (otic); Ophthalmic
Spray	Nasal
Ointment	Topical
Liquid	Ophthalmic
Cream	Topical

Prices

Unit description	Cost	Unit
Gramicidin d powder	240.0USD	g
Neosporin gu irr 40 mg/ml amp	23.12USD	ml
Neosporin + pain relief cream	0.32USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	229 °C	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0039 mg/mL	ALOGPS
logP	4.38	ALOGPS
logP	5.96	ChemAxon
logS	-5.7	ALOGPS
pKa (Strongest Acidic)	11.56	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	16	ChemAxon
Hydrogen Donor Count	20	ChemAxon
Polar Surface Area	519.89 Å²	ChemAxon
Rotatable Bond Count	50	ChemAxon
Refractivity	492.33 m³·mol^-1	ChemAxon
Polarizability	194.73 Å³	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST): Not Available
Spectra: Not Available

Transporters

Details1. P-glycoprotein 1

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

Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. [Article]
Kondratov RV, Komarov PG, Becker Y, Ewenson A, Gudkov AV: Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of P-glycoprotein. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14078-83. doi: 10.1073/pnas.241314798. Epub 2001 Nov 13. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 03, 2022 21:05

Gramicidin D

Identification

Structure for Gramicidin D (DB00027)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Transporters

References