# Lincomycin

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Lincomycin
> Markdown URL: https://mediated.wiki/source/Lincomycin.md
> Source: https://en.wikipedia.org/wiki/Lincomycin
> Source revision: 1329259877
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{more citations needed|date=July 2008}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408578167
| IUPAC_name = (2''S'',4''R'')-''N''-[(1''R'',2''R'')-2-Hydroxy-1-[(2''R'',3''R'',4''S'',5''R'',6''R'')-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
| image = Lincomycin.svg
| image_class = skin-invert-image
| alt = 
| image2 = Lincomycin molecule ball.png 
| image_class2 = bg-transparent
| width2 = 250
| alt2 = Ball-and-stick model of lincomycin

<!-- Clinical data -->
| tradename = Biocine, Lincocin
| Drugs.com = {{drugs.com|monograph|lincomycin-hydrochloride}}
| MedlinePlus = a609005
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_category =  
| routes_of_administration = IM/IV
| ATC_prefix = J01
| ATC_suffix = FF02
| ATC_supplemental = {{ATCvet|J51|FF02}}

| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_CA = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL         / P       / POM / CD / Class A, B, C -->
| legal_US = Rx-only
| legal_status =

<!-- Pharmacokinetic data -->
| bioavailability = N/A
| protein_bound =  
| metabolism =  
| elimination_half-life = 5.4 ± 1.0&nbsp;h after IM or IV administration
| excretion = [Kidney](/source/Kidney) and [bile duct](/source/bile_duct)

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 154-21-2
| PubChem = 3000540
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB01627
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2272112
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BOD072YW0F
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00223
| ChEBI_Ref = {{ebicite|changed|EBI}} 
| ChEBI = 6472
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1447

<!-- Chemical data -->
| C=18 | H=34 | N=2 | O=6 | S=1
| smiles = O=C(N[C@@H]([C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O)[C@H](O)C)[C@H]2N(C)C[C@H](CCC)C2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = OJMMVQQUTAEWLP-KIDUDLJLSA-N
}}

'''Lincomycin''' is a [lincosamide](/source/lincosamide) [antibiotic](/source/antibiotic) that comes from the [actinomycete](/source/actinomycete) ''[Streptomyces lincolnensis](/source/Streptomyces_lincolnensis)''.<ref>{{cite journal | vauthors = Macleod AJ, Ross HB, Ozere RL, Digout G | title = Lincomycin: A New Antibiotic Active Against Staphylococci and Other Gram-Positive Cocci: Clinical and Laboratory Studies | journal = Canadian Medical Association Journal | volume = 91 | issue = 20 | pages = 1056–1060 | date = November 1964 | pmid = 14217764 | pmc = 1928283 }}</ref> A related compound, [clindamycin](/source/clindamycin), is derived from lincomycin by using [thionyl chloride](/source/thionyl_chloride) to replace the 7-hydroxy group with a chlorine atom with inversion of [chirality](/source/chirality).<ref>{{cite journal | vauthors = Birkenmeyer RD, Kagan F | title = Lincomycin. XI. Synthesis and structure of clindamycin. A potent antibacterial agent | journal = Journal of Medicinal Chemistry | volume = 13 | issue = 4 | pages = 616–619 | date = July 1970 | pmid = 4916317 | doi = 10.1021/jm00298a007 }}</ref> It was released for medical use in September 1964.<ref>{{cite journal | vauthors = Duncan IB, Jeans B | title = Lincomycin in hospital practice | journal = Canadian Medical Association Journal | volume = 93 | issue = 13 | pages = 685–691 | date = September 1965 | pmid = 5828940 | pmc = 1928825 }}</ref>

== Uses ==

Although similar in antibacterial spectrum and [mechanism of action](/source/mechanism_of_action) to [macrolides](/source/macrolides), lincomycin is also effective against other organisms including [actinomycete](/source/actinomycete)s and some species of ''[Mycoplasma](/source/Mycoplasma)'' and ''[Plasmodium](/source/Plasmodium)''.{{Citation needed|date=May 2012}}

However, because of its adverse effects and toxicity, it is rarely used today and reserved for patients allergic to [penicillin](/source/penicillin) or where bacteria have developed [resistance](/source/Antibiotic_resistance).

== Clinical pharmacology ==

Intramuscular administration of a single dose of 600&nbsp;mg of Lincomycin produces average peak serum levels of 11.6&nbsp;μg/mL at 60&nbsp;min, and maintains therapeutic levels for 17&nbsp;h to 20&nbsp;h, for most susceptible gram-positive organisms.  Urinary excretion after this dose ranges from 1.8% to 24.8% (mean: 17.3%).

A two-hour intravenous infusion of 600&nbsp;mg of Lincomycin achieves average peak serum levels of 15.9&nbsp;μg/mL and yields therapeutic levels for 14&nbsp;h for most susceptible gram-positive organisms.  Urinary excretion ranges from 4.9% to 30.3% (mean: 13.8%).

The biological half-life after IM or IV administration is 5.4 ± 1.0&nbsp;h.  The serum half-life of lincomycin may be prolonged in patients with severe impairment of renal function, compared to patients with normal renal function.  In patients with abnormal hepatic function, serum half-life may be twofold longer than in patients with normal hepatic function.  [Hemodialysis](/source/Hemodialysis) and [peritoneal dialysis](/source/peritoneal_dialysis) are not effective in removing lincomycin from the serum.

Tissue level studies indicate that [bile](/source/bile) is an important route of excretion.  Significant levels have been demonstrated in the majority of body tissues.  Although lincomycin appears to diffuse in the [cerebrospinal fluid](/source/cerebrospinal_fluid) (CSF), levels of lincomycin in the CSF appear inadequate for the treatment of meningitis.

== Biosynthesis ==

Lincomycin is an [antibiotic](/source/antibiotic) classified as a member of the lincosamide class, which typically features a L-proline amino acid derivative linked through amide group with an eight-carbon aminothio sugar.<ref>{{cite journal | vauthors = Janata J, Kamenik Z, Gazak R, Kadlcik S, Najmanova L | title = Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products | journal = Natural Product Reports | volume = 35 | issue = 3 | pages = 257–289 | date = March 2018 | pmid = 29517100 | doi = 10.1039/c7np00047b | doi-access = free }}</ref> The two units 4-propyl-L-proline and the amino-octose, are each synthesized separately, and are then condensed by LmbD protein, and then further postcondensation reactions involving cleaving of [mycothiol](/source/mycothiol), deacetylation, and S-methylation finally yield lincomycin.

The biosynthesis of the [amino acid](/source/amino_acid) moiety of lincomycin, starts with [tyrosine](/source/tyrosine) which is transformed to 4-propyl-L-proline by the consecutive action of LmbB1, LmbB2, LmbW, LmbA and LmbX proteins. 4-Propyl-L-proline is activated by LmbC and loaded into LmbN, a bifunctional [peptidyl carrier protein](/source/peptidyl_carrier_protein), and is ready for condensation by LmbD.
 
The biosynthetic pathway for production of the amino-octose moiety is almost fully elucidated although the order of the steps still needs further research. Condensation through a [transaldolase](/source/transaldolase) (LmbR) of ribose 5-phosphate (C5) with fructose 6-phosphate or sedoheptulose-7-phosphate (providing a C3 unit) forms the octose (C8). Further transformations involving isomerization (LmbN), 1-phosphorylation (LmbP), 8-dephosphorylation (LmbK), guanosine diphosphate attachment at position 1 (LmbO), 4-epimerization (LmbM), 6-oxidation (LmbL), amination (LmbS), imine reduction (LmbZ) and 8-reduction, are performed to construct the amino-octose unit. LmbT protein exchange GDP by [ergothioneine](/source/ergothioneine) and the condensation with 4-propyl-L-proline and catalysed by LmbD can occur. The amide-linked product between the amino acid and the amino-octose bound to [ergothioneine](/source/ergothioneine) is then the substrate of LmbV, which substitute [ergothioneine](/source/ergothioneine) by [mycothiol](/source/mycothiol). The [mycothiol](/source/mycothiol) moiety is then cleaved by LmbE, and the product is further processed by LmbIH, LmbQ, LmbJ, LmbF and is finally sulphur methylated by LmbG, to afford lincomycin.

== Spectrum of susceptibility ==
Lincomycin is a narrow spectrum antibiotic with activity against Gram-positive and cell wall-less bacteria including pathogenic species of ''Streptococcus'', ''Staphylococcus,'' and ''Mycoplasma''.<ref>{{Cite web | url=https://www.rxlist.com/lincocin-drug/indications-dosage.htm |title = Lincocin (Lincomycin HCL): Uses, Dosage, Side Effects, Interactions, Warning}}</ref> Lincomycin is used to treat severe bacterial infections in patients who cannot use penicillin antibiotics. Lincomycin shows weak activity against most Gram-negative bacteria. The following represents susceptibility ([MIC](/source/minimum_inhibitory_concentration)) data for a few pathogenic bacteria:
* ''Staphylococcus aureus'' - 0.2&nbsp;μg/mL - 32&nbsp;μg/mL
* ''Streptococcus pneumoniae'' - 0.05&nbsp;μg/mL - 0.4&nbsp;μg/mL<ref>{{cite web | title = Lincomycin HCl | work = EP Susceptibility and 0.05 - 0.4 Minimum Inhibitory >50 Concentration Range (μg/mL) Concentration (MIC) Data | date = 6 January 2020 | publisher = TOKU-E | url = http://www.toku-e.com/Assets/MIC/Lincomycin%20HCl%20EP.pdf }}</ref>
* ''Streptococcus pyogenes'' - 0.04&nbsp;μg/mL - 0.8&nbsp;μg/mL<ref>{{Cite web | url=https://antibiotics.toku-e.com/antimicrobial_783.html | archive-url = https://web.archive.org/web/20160303205816/https://antibiotics.toku-e.com/antimicrobial_783.html | archive-date = 3 March 2016 |title = Lincomycin (Lincocin) | work = The Antimicrobial Index Knowledgebase | publisher = TOKU-E }}</ref>

== References ==
{{Reflist}}

{{Macrolides, lincosamides and streptogramins}}

Category:Lincosamides
Category:Drugs developed by Pfizer

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Adapted from the Wikipedia article [Lincomycin](https://en.wikipedia.org/wiki/Lincomycin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Lincomycin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.