Clindamycin (Cleocin)
Cleocin®, Cleocin Pediatric®, Cleocin T®, Cleocin Vaginal®, Clinda-Derm™, Clindets™ | Cleocin Phosphate® | Cleocin® Cream | Clindagel™ | ClindaMax™ | Clindesse™ | Evoclin™
Classification:
- Antiinfective Agents
- Dermatological Agents
- Genitourinary Agents
Description: Clindamycin is an antibiotic structurally similar to lincomycin, from which it is derived. Clindamycin traditionally has been considered an effective anti-anaerobic antibiotic, but it recently has been shown to be effective in combination with pyrimethamine in treating toxoplasmic encephalitis in patients with AIDS. Clindamycin was approved by the FDA in 1970 and is marketed as the hydrochloride salt for oral administration and as the phosphate salt for parenteral, topical or vaginal administration. The FDA approved a single-dose vaginal cream (Clindesse™) for bacterial vaginosis in November 2004. The FDA approved Evoclin™, an aerosol topical foam containing 1% clindamycin, for the treatment of acne vulgaris in December 2004.
Mechanism of Action: Clindamycin binds to the 50 S ribosomal subunits of the bacteria, which inhibits protein synthesis. As with lincomycin, antibacterial activity results from inhibition of protein synthesis. Clindamycin is either bacteriostatic or bactericidal, depending on its concentration at the site of action and on the specific susceptibility of the organism being treated.
Clindamycin is active against a wide range of aerobic gram-positive cocci as well as several anaerobic gram-negative and gram-positive organisms. Many species of streptococci, except for enterococci, and staphylococci are extremely susceptible. Most anaerobes, both gram-positive and gram-negative, are also susceptible. Clindamycin should be used cautiously against Clostridia strains. Clindamycin is a well-known cause of pseudomembranous colitis, possibly due to overgrowth of Clostridia difficile, and 10-20% of strains of Clostridia perfringes can be resistant to clindamycin. Resistance has also been seen in some strains of B. fragilis. One study reported marked antibiotic resistance after treatment of bacterial vaginosis with clindamycin; resistance persisted for up to 90 days after treatment.
In the treatment of acne, topical clindamycin is believed to exert an antibacterial effect on susceptible organisms. Clindamycin also inhibits lipase-producing organisms, reducing the concentration of free fatty acids in sebum, which may be a possible cause of inflammatory lesions associated with acne.
Pharmacokinetics: Clindamycin is administered by the oral, parenteral, topical, and vaginal routes. About 90% of an oral dose of clindamycin is absorbed after oral administration. Absorption from the gut is rapid. The rate but not the extent of absorption can be delayed by food. Clindamycin palmitate and clindamycin phosphate require hydrolysis to form free clindamycin, which occurs readily in the bloodstream. In adults, peak serum concentrations are achieved within 45-60 minutes after oral administration. Peak serum levels are similar after oral administration of either the hydrochloride or the palmitate salt. Peak serum levels following IM administration occur within 3 hours in adults and 1 hour in children. Some systemic absorption does occur after topical administration, depending on the surface area covered. Clindamycin phosphate appears to be less well absorbed through the skin than is the hydrochloride. Topical preparations are marketed as clindamycin phosphate. Clinicians should note that up to 30% of a vaginally applied clindamycin dosage is systemically absorbed.
Oral or parenteral doses are widely distributed into most body tissues, with high concentrations in bone, bile, and urine. CSF concentrations are poor, and clindamycin is not indicated for the treatment of meningitis. It is, however, useful in treating toxoplasma encephalitis. Clindamycin crosses the placenta readily and is distributed into breast milk. Plasma protein binding is 92-94%.
Clindamycin is metabolized to two bioactive metabolites, clindamycin sulfoxide and N-demethylclindamycin, and various inactive metabolites. Following oral dosage, only about 10% is excreted in the urine as active drug and metabolites, and about 3.6% in the feces. The remainder is excreted as inactive metabolites. Probenecid does not affect clindamycin renal elimination. The plasma half-life in adults and children with normal renal function is 2-3 hours. The plasma half-life for premature infants is about 3 times that of healthy adults. Renal impairment and, more significantly, hepatic impairment prolong the elimination of clindamycin. Since clindamycin is minimally excreted by the kidneys, elimination half-life in patients with end-stage renal disease is only slightly prolonged to 3-5 hours. Clindamycin is not removed by hemodialysis or peritoneal dialysis.
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