Yang Si H, Lee Myung G
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Int J Pharm. 2007 Mar 6;332(1-2):17-23. doi: 10.1016/j.ijpharm.2006.11.019. Epub 2006 Nov 11.
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%.
在给大鼠静脉注射（剂量分别为50、100和200mg/kg）和口服（剂量分别为75、150和300mg/kg）克林霉素后，评估了其药代动力学参数。在给大鼠门静脉、胃内和十二指肠内注射150mg/kg剂量的克林霉素后，也评估了其首过效应。静脉注射和口服克林霉素后，该药物的药代动力学参数与剂量无关。因此，绝对口服生物利用度（F）的程度也与口服剂量无关。口服克林霉素（150mg/kg）后，直至24小时有7.68%的口服剂量未被吸收，F值为28.2%。克林霉素的胃首过效应为口服剂量的60.7%。在大鼠中，克林霉素在肺、心脏、肠道和肝脏中的首过效应几乎可以忽略不计（如果有的话）。大鼠中克林霉素的低F值主要归因于相当大的胃首过效应。克林霉素在大鼠胃液和pH值范围为1至13的各种缓冲溶液中稳定。在大鼠血液中，克林霉素的血浆与血细胞分配比为7.59。大鼠中克林霉素的血浆蛋白结合率为67.5%。
