Pharmacokinetics of sildenafil after intravenous and oral administration in rats: hepatic and intestinal first-pass effects |
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Authors: | Shin Hyun S Bae Soo K Lee Myung G |
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Institution: | aCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea |
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Abstract: | 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 50 mg/kg), the dose-normalized AUC values were proportional to intravenous doses studied. However, after oral administration (10, 30, and 100 mg/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. |
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Keywords: | Sildenafil Pharmacokinetics Hepatic and intestinal first-pass effects Rats |
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