Clindamycin excretion

Clindamycin can be administered orally with a high bioavailability. Also formulations for intravenous administration exist. Protein binding is about 90%. It is distributed throughout the body except the CNS. It shows excellent penetration in bone and in empyema and abscesses. It is metabolized in the liver and excreted in the bile. The elimination half-life is about 3 h. Adverse effects include gastrointestinal distress, skin rashes and decreased liver function. Pseudomembranous colitis is relatively frequently seen due to resistance of Clostridium difficile. 

By definition, the fraction that enters the circulatory system is eliminated by extrarenal mechanisms (usually metabolism by the liver and other tissues) and is derived by the difference from renal excretion that is, 1 — Fg. The excretory organs are able to eliminate polar compounds such as tetracycline and tylosin more efficiently than compounds that are highly soluble in lipids (i.e., lipophilic) such as metronidazole, erythromycin, clindamycin, and trimethoporin. Thus, the highly lipophilic compounds will not be eliminated until they are metabolized to more polar intermediates. 

Clindamycin is widely distributed in body lluids and tissues. It is bound to plasma proteins in the circulation. It crosses the placenta and appears in breast milk. Clindamycin is mostly metabolized in the liver and excreted in the bile and urine as parent drug and active metabolites (89). Similarly to lincomycin, metabolism of clindamycin proceeds primarily by oxidation of the sulfur atom to the sulfoxide metabolite and demethylation to the N-desmethyl metabolite (112). 

Both pirlimycin and its sulfoxide metabolite were partially converted to ribonucleotide adducts by gastrointestinal tract microflora and excreted in feces. Such adducts have been well documented as products of antibiotic inactivation by bacteria for a variety of substances including lincomycin and clindamycin (117-119). 

Whereas oral hncomycin has a systemic availability of about 40%, which may be further compromised by food, clindamycin is absorbed from the gastrointestinal tract about 90-100%. Both are eliminated mainly by hepatic metabolism and biliary excretion. 

Since the lincosamides are eliminated by biliary excretion, toxicity would be expected in patients with liver disease. High doses of clindamycin may be hepatotoxic (34). Abnormal liver function tests during treatment with hn-comycin are rare, and only in patients who had taken large doses (over 4 g/day) for more than 3 weeks (6). In another series, intravenous lincomycin 4—18 g/day was not associated with renal or hepatic toxicity (SED-7, 388). 

Lincomycin is widely distributed in the body but does not appear in the CNS in significant concentrations. It is about 90% protein bound. Excretion is mainly through the liver, bile, and urine. Lincomycin s common adverse effects are diarrhea, nausea, and skin rashes. Impaired liver function (with or without jaundice) and neutropenia sometimes occur. Severe diarrhea and enterocolitis have followed clindamycin administration and place a serious restraint on its use. 

Excretion Only -10% of clindamycin is excreted unaltered in the urine small quantities are found in the feces. However, antimicrobial activity persists in feces for at least 5 days after therapy is stopped and growth of clindamycin-sensitive microorganisms may be suppressed for 2 weeks. 

Chndamycin is inactivated by metabolism to A-de-methylchndamycin and clindamycin sulfoxide, which are excreted in the urine and bile. Accumulation of clindamycin can occur in patients with severe hepatic failure, and dosage adjustments may be required. 

A. Classification and Pharmacokinetics The lincosamides lincomycin and clindamycin inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides, though they are not chemically related. Mechanisms of resistance include methylation of the binding site on the 50S ribosomal subunit and enzymatic inactivation. Cross-resistance between lincosamides and macrolides is common. Good tissue penetration occurs after oral absorption. The lincosamides are eliminated partly by metabolism and partly by biliary and renal excretion. 

Antimicrobial drugs that are eliminated via hepatic metabolism or biliary excretion include erythromycin, cefoperazone, clindamycin, doxycycline, isoniazid, ketoconazole, and nafcillin. The answer is (C). 

Clindamycin PO/IV. Hepatic and renal excretion. Reduce dose with impaired liver function. Lincomycin PO. Similar to clindamycin. 

Novak E, Wagner JG and Lamb DJ, Local and systemic tolerance, absorption and excretion of clindamycin hydrochloride after intramuscular administration, Int. /. Clin. Pharm., 3(3),... 

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