Dose-independent pharmacokinetics of clindamycin after intravenous and oral administration to rats: contribution of gastric first-pass effect to low bioavailability.
The pharmacokinetic parameters of clindamycin were evaluated after intravenous (at doses of 50, 100, and 200mg/kg) and oral (at doses of 75, 150, and 300mg/kg) administration of the drug to rats. The first-pass effect of clindamycin was also evaluated after intraportal, intragastric, and intraduodenal administration of the drug at a dose of 150mg/kg to rats. After both intravenous and oral administration of clindamycin, the pharmacokinetic parameters of the drug were dose-independent. Hence, the extent of absolute oral bioavailability (F) was also independent of oral doses. After oral administration of clindamycin (150mg/kg), 7.68% of oral dose was not absorbed up to 24h and F value was 28.2%. The gastric first-pass effect of clindamycin was 60.7% of oral dose. The first-pass effects of clindamycin in the lung, heart, intestine, and liver were almost negligible, if any, in rats. The low F of clindamycin in rats was mainly due to considerable gastric first-pass effect. Clindamycin was stable in rat gastric juice and various buffer solutions having pHs ranging from 1 to 13. The plasma-to-blood cells partition ratio of clindamycin was 7.59 in rat blood. The plasma protein binding of clindamycin in rats was 67.5%.
Yang
Si H
SH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002981:Clindamycin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004386:Duodenum / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D002981:Clindamycin