Shin Hyun S, Bae Soo K, 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. 2006 Aug 31;320(1-2):64-70. doi: 10.1016/j.ijpharm.2006.04.005. Epub 2006 May 26.
Pharmacokinetics of sildenafil after intravenous and oral administration at various doses and first-pass effect at 30 mg/kg were evaluated in rats. After intravenous administration (10, 30, and 50mg/kg), the dose-normalized AUC values were proportional to intravenous doses studied. However, after oral administration (10, 30, and 100mg/kg), the dose-normalized AUC values increased significantly with increasing doses, possibly due to saturation of metabolism of sildenafil in rat intestinal tract. After oral administration (30 mg/kg), approximately 0.626% was not absorbed and F was 14.6%. The AUC after intragastric administration was significantly smaller (71.4% decrease) than that after intraportal administration, however, the values were not significantly different between intragastric and intraduodenal administration. The above data suggested that intestinal first-pass effect of sildenafil was approximately 71% of oral dose in rats. The AUC values after intraportal administration were significantly smaller (49% decrease) than that after intravenous administration. This suggested that hepatic first-pass effect of sildenafil after absorption into the portal vein was approximately 49% of oral dose in rats (approximately 49% was equivalent to approximately 13.7% of oral dose). The low F of sildenafil at a dose of 30 mg/kg in rats could be mainly due to considerable intestinal first-pass effect.
在大鼠中评估了不同剂量静脉注射和口服西地那非后的药代动力学以及30mg/kg剂量下的首过效应。静脉注射（10、30和50mg/kg）后，剂量标准化的AUC值与所研究的静脉注射剂量成比例。然而，口服给药（10、30和100mg/kg）后，剂量标准化的AUC值随剂量增加而显著增加，这可能是由于大鼠肠道中西地那非代谢的饱和。口服给药（30mg/kg）后，约0.626%未被吸收，F为14.6%。胃内给药后的AUC显著小于门静脉内给药后的AUC（降低71.4%），然而，胃内给药和十二指肠内给药之间的值没有显著差异。上述数据表明，西地那非在大鼠中的肠道首过效应约为口服剂量的71%。门静脉内给药后的AUC值显著小于静脉注射后的AUC值（降低49%）。这表明西地那非经门静脉吸收后的肝脏首过效应约为大鼠口服剂量的49%（约49%相当于口服剂量的约13.7%）。大鼠中30mg/kg剂量的西地那非F值较低可能主要是由于显著的肠道首过效应。
