CLINICAL PHARMACOLOGY

Pharmacodynamics

Clindamycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Clindamycin hydrochloride is inactive until hydrolyzed to free clindamycin.

Clindamycin appears to inhibit protein synthesis in susceptible organisms by binding to the 50S subunits of the bacterial ribosome which leads to the inhibition of peptide bond formation. This prevents chain prolongation by blocking transpeptidation, halting bacterial multiplication. Clindamycin’s site of action appears to be the same as that of erythromycin and chloramphenicol.

Antimicrobial Spectrum of Activity  

Clindamycin has shown activity against most isolates of the following microorganisms, both in vitro and in clinical infections:

          Most Gram negative aerobes are resistant to Clindamycin except those mentioned above.

Clindamycin has shown activity in vitro against most strains of the following microorganisms; however, the safety and effectiveness of clindamycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Pharmacokinetics

Approximately 90% of an oral dose is rapidly absorbed from the GI tract. Clindamycin is not inactivated by gastric acidity. Clindamycin’s serum concentrations appear to be predictable, increasing linearly with increasing doses. The extent of absorption and peak serum concentrations of clindamycin are not appreciably affected when administered with food, although peak plasma concentrations may be delayed.

After oral administration of a single 150-mg dose of clindamycin hydrochloride to healthy, fasting adults, peak serum concentrations of clindamycin average 1.9 to 3.9 mcg/mL and are attained within 45 to 60 mins; serum concentrations of clindamycin average 1.5 mcg/mL at 3 hrs and 0.7 mcg/mL at 6 hrs.

Clindamycin is distributed into many body tissues and fluids including saliva, ascitic fluid, pleural fluid, synovial fluid, bone, and bile. However, even in the presence of inflamed meninges, only small amounts of the drug diffuse into the CSF. The concentration of clindamycin in synovial fluid and bone is reported to be 60-80% of concurrent serum concentrations; the degree of penetration does not appear to be affected by joint inflammation. Clindamycin readily crosses the placenta; cord blood concentrations of the drug have been reported to be 46% of concurrent maternal blood concentrations. Clindamycin is distributed into breast milk.

At a concentration of 1 mcg/mL, clindamycin is approximately 93% bound to serum proteins.

Clindamycin’s serum t_1/2 is 2 to 3 hrs in adults and children with normal renal function. The serum t_1/2 is increased slightly in patients with markedly reduced renal or hepatic function. Clindamycin’s serum concentrations are not appreciably affected by hemodialysis, peritoneal dialysis, or prolonged administration in patients with normal renal function.

Clindamycin is partially metabolized to bioactive and inactive metabolites. The major bioactive metabolites are clindamycin sulfoxide and N-demethyl-clindamycin which are excreted in urine, bile, and feces. Approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in the feces as active drug and metabolites within 24 hrs; the remainder is excreted as inactive metabolites. Probenecid has no effect on clindamycin excretion.

Studies to date have not revealed any clinically important differences in the PK of oral or parenteral clindamycin between younger adults and geriatric patients with normal hepatic function and normal (age-adjusted) renal function.