Blood level studies comparing clindamycin palmitate HCl with clindamycin hydrochloride show that both drugs reach their peak active serum levels at the same time, indicating a rapid hydrolysis of the palmitate to the clindamycin.
Serum level studies with clindamycin palmitate HCl in normal pediatric patients weighing 50-100 lbs given 2, 3 or 4 mg/kg every 6 hours (8, 12 or 16 mg/kg/day) demonstrated mean peak clindamycin serum levels of 1.24, 2.25 and 2.44 mcg/mL respectively, one hour after the first dose. By the fifth dose, the 6-hour serum concentration had reached equilibrium. Peak serum concentrations after this time would be about 2.46, 2.98 and 3.79 mcg/mL with doses of 8, 12 and 16 mg/kg/day, respectively. Serum levels have been uniform and predictable from person to person and dose to dose.
Multiple-dose studies in neonates and infants up to 6 months of age show that the drug does not accumulate in the serum and is excreted rapidly. Serum levels exceed the MICs for most indicated organisms for at least six hours following administration of the usually recommended doses of CLEOCIN PEDIATRIC in adults and pediatric patients. Clindamycin is widely distributed in body fluids and tissues (including bones).
No significant levels of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges.
In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly metabolized by Cytochrome P450 3A4 (CYP3A4), with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin.
Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; the remainder is excreted as bioinactive metabolites.
The average serum half-life after doses of CLEOCIN PEDIATRIC is approximately two hours in pediatric patients.
Patients with Renal Impairment
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.
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 – 5.1 h) in the elderly compared to 3.2 hours (range 2.1 – 4.2 h) in younger adults; administration of clindamycin palmitate HCl resulted in a similar elimination half-life value of about 4.5 hours in elderly subjects. However, the extent of absorption is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function1.
Obese Pediatric Patients Aged 2 to Less than 18 Years and Obese Adults Aged 18 to 20 Years
An analysis of pharmacokinetic data in obese pediatric patients aged 2 to less than 18 years and obese adults aged 18 to 20 years demonstrated that clindamycin clearance and volume of distribution, normalized by total body weight, are comparable regardless of obesity.
Mechanism of Action
Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic.
Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the D-zone test.
Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section.
- Staphylococcus aureus (methicillin-susceptible strains)
- Streptococcus pneumoniae (penicillin-susceptible strains)
- Streptococcus pyogenes
- Clostridium perfringens
- Fusobacterium necrophorum
- Fusobacterium nucleatum
- Peptostreptococcus anaerobius
- Prevotella melaninogenica
At least 90% of the microorganisms listed below exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the clindamycin susceptible MIC breakpoint for organisms of a similar type. However, the efficacy of clindamycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
- Staphylococcus epidermidis (methicillin-susceptible strains)
- Streptococcus agalactiae
- Streptococcus anginosus
- Streptococcus mitis
- Streptococcus oralis
- Actinomyces israelii
- Clostridium clostridioforme
- Eggerthella lenta
- Finegoldia (Peptostreptococcus) magna
- Micromonas (Peptostreptococcus) micros
- Prevotella bivia
- Prevotella intermedia
- Propionibacterium acnes