Pharmacology: Pharmacokinetics: Serum level studies with 150 mg oral dose of clindamycin hydrochloride in 24 normal adult volunteers showed that clindamycin was rapidly absorbed after oral administration. An average peak serum level of 2.50 mcg/ml was reached in 45 minutes; serum levels averaged 1.51 mcg/ml at 3 hours and 0.70 mcg/ml at 6 hours. Absorption of an oral dose is virtually complete (90%), and the concomitant administration of food does not appreciably modify the serum concentrations; serum levels have been uniform and predictable from person to person and dose to dose. Serum level studies following multiple doses of clindamycin hydrochloride for up to 14 days show no evidence of accumulation or altered metabolism of drug.
Serum half-life of clindamycin is increased slightly in patients with markedly reduced renal function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Concentrations of clindamycin in the serum increased linearly with increased dose. Serum levels exceed the MIC (Minimum inhibitory concentration) for most indicated organisms for at least six hours following administration of the usually recommended doses.
Clindamycin is widely distributed in body fluids and tissues (including bones). The average biological half-life is 2.4 hours. Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; The remainder is excreted as bio-inactive metabolites. Doses of up to 2 grams of clindamycin per day for 14 days have been well tolerated by healthy volunteers, except that the incidence of gastrointestinal side effects is greater with the higher doses.
No significant levels of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges. Pharmacokinetic studies in elderly volunteers (61-79 years) and younger adults (18-39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, elimination half-life is increased to approximately 4.0 hours (range 3.4-5.1h) in the elderly compared to 3.2 hours (range 2.1-4.2h) in younger adults. The extend of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function.
Microbiology: Clindamycin has been shown to have in vitro activity against isolates of the following organisms: Aerobic gram-positive cocci, including: Staphylococcus aureus; Staphylococcus epidermidis (penicillinase and nonpenicillinase producing strains); when tested by in vitro methods some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin; Streptoccoci (except Streptococcus faecalis); Pneumococci.
Anaerobic gram-negative bacilli, including: Bacteriodes species (including Bacteroides fragilis group and Bacteroides melaninogenicus group); Fusobacterium species.
Anaerobic gram-positive non-sporeforming bacilli, including: Propionibacterium, Eubacterium, Actinomyces species.
Anaerobic and microaerophilic gram-positive cocci, including: Peptococcus species; Peptostreptococcus species, Microaerophilic streptococci.
Clostridia: Clostridia are more resistant than most anaerobes to Clindamycin. Most Clostridium perfringens are susceptible, but other species, e.g., Clostridium sporogenes and Clostridium tertium are frequently resistant to clindamycin.
Susceptibility testing should be done.
Cross resistance has been demonstrated between clindamycin and lincomycin. Antagonism has been demonstrated between clindamycin and erythromycin.