Yoshimura M, Kojima J, Ito T, Fujii M, Suzuki J
J Pharmacobiodyn. 1985 Jul;8(7):503-12. doi: 10.1248/bpb1978.8.503.
The pharmacokinetic parameters of nipradilol (NIP), a new potent antihypertensive and antianginal agent, and propranolol were determined after oral, intravenous and intraportal administration to the beagle dog implanted with cannula in portal vein at a dose of 1 mg/kg. Orally administered NIP underwent extensive first-pass metabolism leading to low bioavailability (11%), despite of complete gastrointestinal absorption. On the constant infusion for 30 min into the portal vein, hepatic extraction ratio was 0.71. The reduction in the systemic availability of orally administered NIP could partly be attributed to the fact that denitration and glucuronidation of NIP occur primarily in the intestinal tract and liver, respectively. Following oral administration of NIP, smaller amount of unchanged drug (1.9%) was excreted into the urine than that of intravenous administration (5.8%). However, in the qualitative and the quantitative aspects on urinary metabolic patterns, there was no appreciable influence of the route of administration. On the other hand, the systemic availability and the hepatic extraction ratio of propranolol were 11% and 0.86, respectively, suggesting that the first-pass metabolism through the liver actually contributes to the reduced availability.
对门静脉插管的比格犬以1mg/kg的剂量口服、静脉注射和门静脉注射后，测定了新型强效抗高血压和抗心绞痛药物尼普地洛（NIP）和普萘洛尔的药代动力学参数。尽管尼普地洛经胃肠道完全吸收，但口服后经历广泛的首过代谢，导致生物利用度较低（11%）。以门静脉持续输注30分钟时，肝脏提取率为0.71。口服尼普地洛全身可用性降低部分可归因于尼普地洛的脱硝和葡萄糖醛酸化分别主要发生在肠道和肝脏。口服尼普地洛后，排泄到尿液中的原形药物量（1.9%）比静脉注射（5.8%）少。然而，在尿代谢模式的定性和定量方面，给药途径没有明显影响。另一方面，普萘洛尔的全身可用性和肝脏提取率分别为11%和0.86，表明通过肝脏的首过代谢实际上导致了可用性降低。
