Lincomycin
Identification
- Summary
Lincomycin is an antibiotic indicated only for the treatment of serious infections and is typically reserved for use in cases of penicillin allergy or where penicillin is inappropriate.
- Brand Names
- Lincocin
- Generic Name
- Lincomycin
- DrugBank Accession Number
- DB01627
- Background
Lincomycin is a lincosamide antibiotic first isolated from the soil bacterium Streptomyces lincolnensis in Lincoln, Nebraska.2 Clinical use of lincomycin has largely been superseded by its semisynthetic derivative clindamycin due to its higher efficacy and a wider range of susceptible organisms, though lincomycin remains in use.1,2
Lincomycin was approved by the FDA on December 29, 1964.10
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
Structure for Lincomycin (DB01627)
- Weight
- Average: 406.54
Monoisotopic: 406.213757997 - Chemical Formula
- C18H34N2O6S
- Synonyms
- Cillimycin
- LCM
- Lincomicina
- Lincomycin
- Lincomycine
- Lincomycinum
- External IDs
- U-10,149
- U-10149
Pharmacology
- Indication
Lincomycin is indicated for the treatment of serious bacterial infections by susceptible strains of streptococci, pneumococci, and staphylococci in patients who are allergic to penicillins or for situations in which a penicillin is deemed inappropriate. As with all antibacterial agents, lincomycin should only be used to treat infections proven or strongly suspected to be caused by susceptible bacteria.10
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from Streptomyces lincolnensis. Like clindamycin, lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as Haemophilus spp. It is also effective against anaerobic bacteria, though in this regard clindamycin is generally more potent.1,2 Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to Staphylococcus spp. and Streptococcus spp., with additional activity noted in vitro.10
Lincomycin should be used with caution due to its association with severe cutaneous hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis, and its potential to precipitate Clostridium difficile associated diarrhea (CDAD), which may lead to fatal colitis. Special care should therefore be exercised when used in elderly patients, individuals with a history of gastrointestinal disease, and those with a history of asthma or significant allergies. Lincomycin for injection may contain benzyl alcohol as a preservative, which has been associated with gasping syndrome in pediatric patients. The serum half-life is extended in patients with hepatic/renal impairment and may require dose adjustments and additional monitoring. Like all antibiotics, lincomycin use may cause overgrowth of non-susceptible organisms, which should be considered.10
- Mechanism of action
Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit.1,2 Detailed investigations into the mechanism of the related lincosamide clindamycin suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds.3,4,5 This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary.5,6 Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of Staphylococcus aureus show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to clindamycin.6 This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611.2,6
Target Actions Organism A23S ribosomal RNA binderEnteric bacteria and other eubacteria - Absorption
A 600 mg dose of lincomycin administered over two hours intravenously results in an average Cmax of 15.9 μg/mL while the same dose given by intramuscular injection produces an average Cmax of 11.6 μg/mL after 60 minutes.10 Lincomycin administered intramuscularly to healthy adult male volunteers in doses between 600 and 1500 mg had an AUC0-∞ between 92.22 and 159.91 μg*h/mL.7 A similar study using intravenous infusion of 600-2400 mg lincomycin found AUC0-∞ values between 72.5 and 212.8 μg*h/mL.8 Overall, the AUC increases disproportionally to dose.7,8
- Volume of distribution
Lincomycin administered intravenously to healthy adult males had a steady-state volume of distribution of 63.8 ± 23.8, 78.8 ± 17.0, and 105.1 ± 43.1 L for 600, 1200, and 2400 mg doses, respectively.8
- Protein binding
Lincomycin serum protein binding varies greatly depending on the dose, ranging from 28 to 86% in one study,8 and generally decreases with increasing serum concentration suggesting saturable binding.7,8 It has been suggested that lincomycin, like clindamycin, is primarily bound to α1-acid glycoprotein,8 which is consistent with later studies in humans and animals.9
- Metabolism
Lincomycin metabolism is poorly defined, though the primary product recovered following administration in humans is unchanged lincomycin.11
- Route of elimination
Following a 600 mg dose of lincomycin given either intramuscularly or intravenously, the urinary excretion ranges from 1.8-30.3% of the administered dose. Bile is also thought to be an important route of elimination. Dose adjustments are required in patients with either renal or hepatic impairment.10
- Half-life
Lincomycin has a biological half-life of 5.4 ± 1.0 hours following intramuscular or intravenous administration, which is prolonged in patients with impaired hepatic or renal function.10
- Clearance
Lincomycin administered intravenously to healthy adult males had a clearance of 9.9 ± 2.5, 10.0 ± 2.0, and 11.8 ± 2.4 L/h for 600, 1200, and 2400 mg doses, respectively.8
- Adverse Effects
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
Toxicity information regarding lincomycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as gastrointestinal effects including colitis, secondary infections, and severe hypersensitivity reactions. Symptomatic and supportive measures are recommended. It is important to note that hemodialysis and peritoneal dialysis do not appreciably affect lincomycin serum concentrations.10
- Pathways
Pathway Category Lincomycin Action Pathway Drug action - 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 Integrate drug-drug
interactions in your softwareAcenocoumarol The risk or severity of bleeding can be increased when Lincomycin is combined with Acenocoumarol. Acetophenazine Acetophenazine may increase the neurotoxic activities of Lincomycin. Alimemazine Alimemazine may increase the neurotoxic activities of Lincomycin. Amisulpride Lincomycin may increase the neurotoxic activities of Amisulpride. Amitriptyline Amitriptyline may increase the neurotoxic activities of Lincomycin. Amitriptylinoxide Lincomycin may increase the neurotoxic activities of Amitriptylinoxide. Amoxapine Amoxapine may increase the neurotoxic activities of Lincomycin. Aripiprazole Aripiprazole may increase the neurotoxic activities of Lincomycin. Aripiprazole lauroxil Lincomycin may increase the neurotoxic activities of Aripiprazole lauroxil. Ascorbic acid The therapeutic efficacy of Lincomycin can be decreased when used in combination with Ascorbic acid. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Product Ingredients
Ingredient UNII CAS InChI Key Lincomycin hydrochloride GCW8Y9936L 859-18-7 POUMFISTNHIPTI-BOMBIWCESA-N Lincomycin hydrochloride monohydrate M6T05Z2B68 7179-49-9 LFZGYTBWUHCAKF-DCNJEFSFSA-N - International/Other Brands
- Lincobect / Lincorex
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lincocin Capsule 500 mg Oral Pfizer Canada Ulc 1964-12-31 2006-08-02 Canada 
Lincocin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival Pharmacia and Upjohn Company LLC 1964-12-29 Not applicable US 
Lincocin Solution 300 mg / mL Intramuscular; Intravenous Pfizer Canada Ulc 1964-12-31 2016-05-06 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lincomycin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival Praxgen Pharmaceuticals LLC 2021-03-30 Not applicable US Lincomycin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival X-GEN Pharmaceuticals, Inc. 2015-07-05 Not applicable US Lincomycin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival General Injectables and Vaccines, Inc. 2020-11-06 Not applicable US Lincomycin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival A-S Medication Solutions 2015-07-05 Not applicable US Lincomycin Injection, solution 300 mg/1mL Intramuscular; Intravenous; Subconjunctival X-GEN Pharmaceuticals, Inc. 2015-07-05 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image LINKOSOL 600 MG 1 AMPUL Lincomycin (600 mg/2ml) Injection Intramuscular; Intravenous OSEL İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey 
Categories
- ATC Codes
- J01FF02 — Lincomycin
- Drug Categories
- Agents that produce neuromuscular block (indirect)
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Carbohydrates
- Enzyme Inhibitors
- Glycosides
- Lincosamides
- Macrolides, Lincosamides and Streptogramins
- Neurotoxic agents
- Protein Synthesis Inhibitors
- Pyrrolidines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resulting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Proline and derivatives
- Alternative Parents
- Alpha amino acid amides / Thioglycosides / Pyrrolidinecarboxamides / Monosaccharides / N-alkylpyrrolidines / Oxanes / Monothioacetals / Trialkylamines / Secondary carboxylic acid amides / Secondary alcohols show 8 more
- Substituents
- Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid amide / Amine / Azacycle / Carbonyl group / Carboxamide group / Glycosyl compound / Hydrocarbon derivative / Monosaccharide show 23 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- monocarboxylic acid amide, pyrrolidinecarboxamide, L-proline derivative, carbohydrate-containing antibiotic, S-glycosyl compound (CHEBI:6472)
- Affected organisms
- Enteric bacteria and other eubacteria
Chemical Identifiers
- UNII
- BOD072YW0F
- CAS number
- 154-21-2
- InChI Key
- OJMMVQQUTAEWLP-KIDUDLJLSA-N
- InChI
- InChI=1S/C18H34N2O6S/c1-5-6-10-7-11(20(3)8-10)17(25)19-12(9(2)21)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,21-24H,5-8H2,1-4H3,(H,19,25)/t9-,10-,11+,12-,13+,14-,15-,16-,18-/m1/s1
- IUPAC Name
- (2S,4R)-N-[(1R,2R)-2-hydroxy-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
- SMILES
- [H][C@]1(C[C@@H](CCC)CN1C)C(=O)N[C@H]([C@@H](C)O)[C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O
References
- Synthesis Reference
Alexander D. Argoudelis, David W. Stroman, "Process of producing lincomycin nucleotides." U.S. Patent US4464466, issued June, 1972.
US4464466- General References
- Spizek J, Rezanka T: Lincomycin, clindamycin and their applications. Appl Microbiol Biotechnol. 2004 May;64(4):455-64. doi: 10.1007/s00253-003-1545-7. Epub 2004 Feb 5. [Article]
- Spizek J, Rezanka T: Lincosamides: Chemical structure, biosynthesis, mechanism of action, resistance, and applications. Biochem Pharmacol. 2017 Jun 1;133:20-28. doi: 10.1016/j.bcp.2016.12.001. Epub 2016 Dec 7. [Article]
- Verdier L, Bertho G, Gharbi-Benarous J, Girault JP: Lincomycin and clindamycin conformations. A fragment shared by macrolides, ketolides and lincosamides determined from TRNOE ribosome-bound conformations. Bioorg Med Chem. 2000 Jun;8(6):1225-43. doi: 10.1016/s0968-0896(00)00081-x. [Article]
- Kouvela EC, Petropoulos AD, Kalpaxis DL: Unraveling new features of clindamycin interaction with functional ribosomes and dependence of the drug potency on polyamines. J Biol Chem. 2006 Aug 11;281(32):23103-10. doi: 10.1074/jbc.M603263200. Epub 2006 Jun 7. [Article]
- Kostopoulou ON, Papadopoulos G, Kouvela EC, Kalpaxis DL: Clindamycin binding to ribosomes revisited: foot printing and computational detection of two binding sites within the peptidyl transferase center. Pharmazie. 2013 Jul;68(7):616-21. [Article]
- Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A: Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus. Nucleic Acids Res. 2017 Sep 29;45(17):10284-10292. doi: 10.1093/nar/gkx658. [Article]
- Smith RB, Lummis WL, Monovich RE, DeSante KA: Lincomycin serum and saliva concentrations after intramuscular injection of high doses. J Clin Pharmacol. 1981 Oct;21(10):411-7. doi: 10.1002/j.1552-4604.1981.tb01742.x. [Article]
- Gwilt PR, Smith RB: Protein binding and pharmacokinetics of lincomycin following intravenous administration of high doses. J Clin Pharmacol. 1986 Feb;26(2):87-90. doi: 10.1002/j.1552-4604.1986.tb02911.x. [Article]
- Son DS, Osabe M, Shimoda M, Kokue E: Contribution of alpha 1-acid glycoprotein to species difference in lincosamides-plasma protein binding kinetics. J Vet Pharmacol Ther. 1998 Feb;21(1):34-40. doi: 10.1046/j.1365-2885.1998.00111.x. [Article]
- FDA Approved Drug Products: Lincocin (lincomycin) injection [Link]
- EMA Committee Report Lincomycin Sep 1998 [Link]
- Cayman Chemical: lincomycin MSDS [Link]
- External Links
- KEGG Drug
- D00223
- KEGG Compound
- C06812
- PubChem Compound
- 3000540
- PubChem Substance
- 46506668
- ChemSpider
- 2272112
- BindingDB
- 50335522
- 6398
- ChEBI
- 6472
- ChEMBL
- CHEMBL1447
- ZINC
- ZINC000003982483
- Therapeutic Targets Database
- DAP000839
- PharmGKB
- PA164749212
- PDBe Ligand
- 3QB
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lincomycin
- PDB Entries
- 4wh5 / 5hkv
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Unknown Status Treatment Cellulitis 1 1 Completed Not Available Bacterial Infections 1 0 Terminated Treatment Osteomyelitis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Bimeda Inc.
- Carlisle Laboratories Inc.
- Clint Pharmaceutical Inc.
- Dispensing Solutions
- Keene Pharmaceuticals Inc.
- Llorens Pharmaceutical
- Martin Surgical Supply
- Medisca Inc.
- Nord Ost Corp.
- Pharmacia Inc.
- Preferred Pharmaceuticals Inc.
- Raz Co. Inc.
- Dosage Forms
Form Route Strength Solution Intramuscular 600 mg Solution Intramuscular; Intravenous 600 mg Powder Oral Powder Capsule Oral Injection, solution Intramuscular; Intravenous; Subconjunctival 300 mg/1mL Injection, solution Parenteral Solution Intramuscular; Intravenous 300 mg / mL Capsule Oral 250 mg Solution Injection, solution Intramuscular; Intravenous Syrup Oral Capsule Oral 500 MG Injection Intramuscular; Intravenous Injection, solution 300 mg/1ml Solution 300 mg/1ml - Prices
Unit description Cost Unit Lincocin 300 mg/ml vial 7.79USD ml Lincomycin hcl powder 3.29USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 187-190 https://www.scbt.com/p/lincomycin-b-hydrochloride-11021-35-5 water solubility freely soluble FDA Label logP 0.56 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 29.3 mg/mL ALOGPS logP 0.5 ALOGPS logP -0.32 ChemAxon logS -1.1 ALOGPS pKa (Strongest Acidic) 12.37 ChemAxon pKa (Strongest Basic) 7.97 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 5 ChemAxon Polar Surface Area 122.49 Å2 ChemAxon Rotatable Bond Count 7 ChemAxon Refractivity 102.67 m3·mol-1 ChemAxon Polarizability 43.65 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.5937 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.7945 P-glycoprotein inhibitor I Non-inhibitor 0.6755 P-glycoprotein inhibitor II Non-inhibitor 0.5633 Renal organic cation transporter Non-inhibitor 0.8868 CYP450 2C9 substrate Non-substrate 0.8417 CYP450 2D6 substrate Non-substrate 0.8837 CYP450 3A4 substrate Substrate 0.6389 CYP450 1A2 substrate Non-inhibitor 0.9222 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9269 CYP450 2C19 inhibitor Non-inhibitor 0.9203 CYP450 3A4 inhibitor Non-inhibitor 0.9342 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9563 Ames test Non AMES toxic 0.7696 Carcinogenicity Non-carcinogens 0.9482 Biodegradation Not ready biodegradable 0.9622 Rat acute toxicity 2.5777 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9847 hERG inhibition (predictor II) Non-inhibitor 0.7163
Spectra
- Mass Spec (NIST)
- Download (7.07 KB)
- Spectra
Targets
References
- Verdier L, Bertho G, Gharbi-Benarous J, Girault JP: Lincomycin and clindamycin conformations. A fragment shared by macrolides, ketolides and lincosamides determined from TRNOE ribosome-bound conformations. Bioorg Med Chem. 2000 Jun;8(6):1225-43. doi: 10.1016/s0968-0896(00)00081-x. [Article]
- Kouvela EC, Petropoulos AD, Kalpaxis DL: Unraveling new features of clindamycin interaction with functional ribosomes and dependence of the drug potency on polyamines. J Biol Chem. 2006 Aug 11;281(32):23103-10. doi: 10.1074/jbc.M603263200. Epub 2006 Jun 7. [Article]
- Kostopoulou ON, Papadopoulos G, Kouvela EC, Kalpaxis DL: Clindamycin binding to ribosomes revisited: foot printing and computational detection of two binding sites within the peptidyl transferase center. Pharmazie. 2013 Jul;68(7):616-21. [Article]
- Matzov D, Eyal Z, Benhamou RI, Shalev-Benami M, Halfon Y, Krupkin M, Zimmerman E, Rozenberg H, Bashan A, Fridman M, Yonath A: Structural insights of lincosamides targeting the ribosome of Staphylococcus aureus. Nucleic Acids Res. 2017 Sep 29;45(17):10284-10292. doi: 10.1093/nar/gkx658. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Gwilt PR, Smith RB: Protein binding and pharmacokinetics of lincomycin following intravenous administration of high doses. J Clin Pharmacol. 1986 Feb;26(2):87-90. doi: 10.1002/j.1552-4604.1986.tb02911.x. [Article]
- Son DS, Osabe M, Shimoda M, Kokue E: Contribution of alpha 1-acid glycoprotein to species difference in lincosamides-plasma protein binding kinetics. J Vet Pharmacol Ther. 1998 Feb;21(1):34-40. doi: 10.1046/j.1365-2885.1998.00111.x. [Article]
Drug created on August 29, 2007 21:12 / Updated on July 28, 2021 15:00