| Identification | More | [Name]
Clindamycin | [CAS]
18323-44-9 | [Synonyms]
CLINDAMYCIN
-1-thio-trans-alpha-l-threo-d-galacto-octopyranoside
7-cdl
7-chloro-7-deoxylincomycin
7-chlorodeoxylincomycin
7-chlorolincomycin
7-deoxy-7(s)-chlorolincomycin
chlolincocin
clindamycine
clinimycin
clinimycin(rescinded)
dalacinc
methyl7-chloro-6,7,8-trideoxy-6-(1-methyl-4-l-threo-d-galacto-octopyranosid
methyl7-chloro-6,7,8-trideoxy-6-(1-methyl-4-propyl-l-2-pyrrolidinecarboxamido)
sobelin
trans-alpha-propyl-l-2-pyrrolidinecarboxamido)-1-thio
L-threo-.alpha.-D-galacto-Octopyranoside, methyl 7-chloro-6,7,8-trideoxy-6-(2S,4R)-1-methyl-4-propyl-2-pyrrolidinylcarbonylamino-1-thio-
CLINDAMYCIN-HYDROCHLORIDE-ETHANOL(INTERMEDIATE)
Clindamycin (base and/or unspecified salts)
(2S,4R)-N-[(1S,2S)-2-Chloro-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide | [EINECS(EC#)]
242-209-1 | [Molecular Formula]
C18H33ClN2O5S | [MDL Number]
MFCD00072005 | [Molecular Weight]
424.98 | [MOL File]
18323-44-9.mol |
| Hazard Information | Back Directory | [Uses]
Clindamycin is a semi-synthetic analogue of lincomycin, prepared by chloride substitution of the exocyclic sugar hydroxy group. This affords a more hydrophobic compound with improved pharmacodynamics. Like other members of the lincosamide family, clindamycin is a broad spectrum antibiotic with activity against anaerobic bacteria and protozoans. Clindamycin acts by binding to the 23S ribosomal subunit, blocking protein synthesis. Clindamycin has been extensively studied with over 8,000 literature citations. | [Definition]
ChEBI: A carbohydrate-containing antibiotic that is the semisynthetic derivative of lincomycin, a natural antibiotic. | [Description]
Clindamycin, a derivative of lincomycin, was fi rst isolated from Streptomyces lincolnesis in 1962 and became commercially available in 1966. It replaced lincomycin use because of its better absorption and clinical spectrum. It is active against gram-positive, gram-negative, and anaerobic organisms. | [Originator]
Dalacin-C,Diethelm,Switz.,1968 | [Indications]
Clindamycin (Cleocin), 300 to 450 mg/day, is an extremely effective agent for
acne. | [Manufacturing Process]
The following procedure is described in US Patent 3,475,407. A solution of 50
g of lincomycin hydrochloride, 120 g of triphenylphosphine, and 500 ml of
acetonitrile in a 3 liter flask equipped with a stirrer was cooled in an ice bath
and 500 ml of carbon tetrachloride was added in one portion. The reaction
mixture was then stirred for 18 hours without addition of ice to the cooling
bath. The reaction was evaporated to dryness under vacuum on a 50° to 60°C
water bath, yielding a clear, pale yellow viscous oil. An equal volume of water
was added and the mixture shaken until all of the oil was dissolved. The
resulting suspension of white solid (Ph3PO) was filtered through a sintered
glass mat and discarded. The filtrate was adjusted to pH 11 by addition of 6 N
aqueous sodium hydroxide. A solid precipitated.
The resulting slurry was extracted with four 300 ml portions of chloroform.
The aqueous phase was discarded. The combined chloroform extract was
washed once with 100 ml of saturated aqueous sodium chloride solution and
the sodium chloride phase was discarded. The chloroform phase was
evaporated to dryness under vacuum on a 50° to 60°C water bath and an
equal volume of methanol was added to the residue and the resulting solution
heated at reflux for 1 hour. The methanol solution was evaporated to dryness
under vacuum on a 50° to 60°C water bath. The residue was a clear pale
yellow viscous oil. An equal volume of water and 10 ml of 37% aqueous HCl
was added and the resultant was shaken until the oil dissolved and a white
solid (more Ph3PO) remained in suspension. The suspension was filtered
through a sintered glass mat at pH 1 to 2 and the solid discarded.
The filtrate was extracted twice with 100 ml of carbon tetrachloride. The
carbon tetrachloride phase was discarded. The aqueous phase was adjusted to
pH 11 by addition of 6 N aqueous sodium hydroxide and extracted four times
with 300 ml portions of chloroform. The combined chloroform extract was
washed three times with 100 ml of saturated aqueous sodium chloride
solution and the sodium chloride phase was discarded. The chloroform extract
was dried over anhydrous magnesium sulfate, filtered and the filtrate
evaporated to dryness under vacuum on a 50° to 60 °C water bath. The
residue was a clear, colorless glass weighing 45 g analyzing about 95% 7(S)-
chloro-7-deoxylincomycin. To the crude product there was added 100 ml of
ethanol with warming until a clear solution was obtained. Then 150 ml ethyl
acetate was added and the resultant filtered through a glass mat and the
filtrate adjusted to pH 1 by the addition of saturated ethanolic HCl.
Crystallization soon occurred. The resultant was allowed to stand at 0°C for
18 hours and then filtered through a sintered glass mat. The solid was dried
under vacuum at 60°C for 18 hours yielding 35 g, a 67% yield of 7(S)-chloro-
7-deoxylincomycin hydrochloride as an ethanol solvate. | [Brand name]
Cleocin (Pharmacia &
Upjohn). | [Therapeutic Function]
Antibacterial | [Biological Activity]
Clindamycin is active against most anaerobes including most anaerobic grampositive cocci, nonspore forming bacilli, Clostridium (except C. diffi cile and some non-perfringens species), anaerobic gram-negative bacilli (except Fusobacterium varium ), and anaerobic gram-positive nonspore forming bacilli.
It is active against most aerobic gram-positive organisms, including viridans streptococci, most strains of pneumococci, and other strains of streptococcal organisms (except Enterococcus ). It is active against MSSA. | [Mechanism of action]
Clindamycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. The use of clindamycin with macrolides is not recommended since both of them compete for binding sites to the 50S subunit. | [Clinical Use]
Clindamycin is effective in the treatment of most infections secondary to anaerobes and gram-positive cocci. It can be used for anaerobic pulmonary, intra-abdominal, gynecologic, pelvic, diabetic foot, and decubitus ulcer infections. Another appropriate agent should be added since the majority of these infections are polymicrobial. It can also be used as an alternative agent for patients with severe penicillin allergy. It is also used to treat Clostridium perfringens infection.
Oral preparations of clindamycin and vaginal cream are alternatives to metronidazole for the treatment of bacterial vaginosis. Topical solution is used for treatment of acne vulgaris and rosacea.
Clindamycin is extensively metabolized by the liver and the half-life is prolonged in patients with cirrhosis and hepatitis. Dose reductions are recommended in patients with acute liver disease. | [Side effects]
The most commonly observed adverse effect is diarrhea. The reported incidence of C. difficile colitis in patients treated with clindamycin varies from 0.1 to 10%. The syndrome may be fatal. If the patient develops C. difficile colitis, clindamycin should be discontinued and the patient should be treated for C. difficile . Other side effects include rash, nausea, vomiting, diarrhea, flatulence, abdominal distension, anorexia, and transient elevation of liver enzymes. Other less common events, such as fever, neutropenia, thrombocytopenia, and eosinophilia have been reported. | [Synthesis]
Clindamycin, methyl-[7-chloro-6,7,8-trideoxy-6-trans-(1-methyl-4-propylL-2-pyrrollidin-carboxamido)-1-thio-L-threo-α-D-galacto-octapyranoside] (32.5.2), which
is a 7(S)-chloro-7-deoxy derivative of lincomycin, is synthesized by replacing the hydroxyl
group of lincomycin (32.5.1) at C7 by treating it with triphenyl phophine in acetonitrile
(Raydon reagent), in which a configuration transformation takes place in the given carbo hydrate. | [Veterinary Drugs and Treatments]
Topical clindamycin is an optional topical treatment for feline acne.
Clindamycin inhibits bacterial protein synthesis by binding to the 50S ribosome; primary activity is against anaerobic and grampositive
aerobic bacteria. For more information on the pharmacology of clindamycin, refer to the monograph for systemic use found in
the main section. | [Drug interactions]
Potentially hazardous interactions with other drugs
Ciclosporin: may cause reduced ciclosporin levels.
Erythromycin: antagonism demonstrated in vitro;
manufacturers recommend that the two drugs should
not be administered concurrently.
Muscle relaxants: enhanced neuromuscular blockade. | [Metabolism]
Clindamycin undergoes metabolism, presumably in the
liver, to the active N-demethyl and sulfoxide metabolites,
and also to some inactive metabolites. About 10% of a
dose is excreted in the urine as active drug or metabolites
and about 4% in the faeces; the remainder is excreted as
inactive metabolites. Excretion is slow, and takes place
over several days |
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