Medyclin Mechanism of Action

Pharmacology: Pharmacodynamics: Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process.
Pharmacodynamic effects: Efficacy is related to the time period over which the agent level is above the minimum inhibitory concentration (MIC) of the pathogen (%T/MIC).
Resistance: Resistance to clindamycin is most often due to mutations at the rRNA antibiotic binding site or methylation of specific nucleotides in the 23S RNA of the 50S ribosomal unit. These alterations can determine in vitro cross resistance to macrolides and streptogramins B (MLS phenotype). Resistance is occasionally due to alterations in ribosomal proteins. Resistance to clindamycin may be inducible by macrolides in macrolide-resistant bacterial isolates. Inducible resistance can be demonstrated with a disk test (D-zone test) or in broth. Less frequently encountered resistance mechanisms involve modification of the antibiotic and active efflux. There is complete cross resistance between clindamycin and lincomycin. As with many antibiotics, the incidence of resistance varies with the bacterial species and the geographical area. The incidence of resistance to clindamycin is higher among methicillin-resistant staphylococcal isolates and penicillin-resistant pneumococcal isolates than among organisms susceptible to these agents.
Antimicrobial activity: Clindamycin has been shown to have in vitro activity against most isolates of the following organisms.
Aerobic bacteria: Gram-positive bacteria: Staphylococcus aureus (methicillin-susceptible isolates); Coagulase-negative staphylococci (methicillin-susceptible isolates); Streptococcus pneumoniae (penicillin-susceptible isolates); Beta-hemolytic streptococci groups A, B, C, and G; Viridans group streptococci; Corynebacterium spp.
Gram-negative bacteria: Chlamydia trachomatis.
Anaerobic bacteria: Gram-positive bacteria: Actinomyces spp; Clostridium spp. (except Clostridium difficile); Eggerthella (Eubacterium) spp.; Peptococcus spp.; Peptostreptococcus spp. (Finegoldia magna, Micromonas micros); Propionibacterium acnes.
Gram-negative bacteria: Bacteriodes spp.; Fusobacterium spp.; Gardnerella vaginalis, Prevotella spp.
Fungi: Pneumocystis jirovecii.
Protozoans: Toxoplasma gondii; Plasmodium falciparum.
Pharmacokinetics: Some level studies with a 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 uniformed 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). In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly oxidized by CYP3A4, with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin. 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 bioinactive 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 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. The extent 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.
Toxicology: Preclinical safety data: Carcinogenesis: Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.
Mutagenesis: Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Impairment of Fertility: Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 11 times the highest recommended adult human dose based on mg/m²) revealed no effects on fertility or mating ability.
In oral embryo fetal development studies in rats and subcutaneous embryo fetal development studies in rats and rabbits, no developmental toxicity was observed except at doses that produced maternal toxicity.