Högstedt S, Lindberg B S, Regårdh C G, Moström U, Rane A
Department of Obstetrics and Gynacology, University Hospital, Uppsala, Sweden.
Pharmacol Toxicol. 1990 Jan;66(1):32-6. doi: 10.1111/j.1600-0773.1990.tb00697.x.
Five pregnant Rhesus monkeys were catheterized in the hepatic and femoral veins. They were simultaneously given 168 or 176 micrograms of 3H-metoprolol intravenously, and 9 mg of metoprolol per kg body weight orally. The same procedure was repeated a few months after delivery. Analyses of the unlabelled drug in blood were made by gas-chromatography and of the 3H-labelled metoprolol, by liquid scintillation. The apparent volume of distribution as well as the terminal half-lives of metoprolol were in the same range during pregnancy and in non-pregnancy. The oral bioavailability of metoprolol was lower (6-22%) during pregnancy than in non-pregnancy (9-49%). The apparent oral clearance and the intrinsic hepatic clearance were in a similar range although there was a greater variation in the intrinsic clearance values. The former clearance estimate was lower in the non-pregnant state only for three of the five animals. The systemic clearance varied very little and was in the same range during pregnancy and in non-pregnancy. The changes in apparent oral clearance and in oral bioavailability of metoprolol between the pregnant and non-pregnant Rhesus monkey are similar to the changes observed in pregnant women, although the absolute values are different.
五只怀孕的恒河猴经肝静脉和股静脉插管。它们同时静脉注射168或176微克的³H-美托洛尔，并口服每千克体重9毫克的美托洛尔。分娩后几个月重复相同程序。通过气相色谱法分析血液中未标记的药物，通过液体闪烁法分析³H-标记的美托洛尔。在怀孕期间和美托洛尔的非孕期，其表观分布容积和终末半衰期处于相同范围。怀孕期间美托洛尔的口服生物利用度低于非孕期（6 - 22%），而非孕期为（9 - 49%）。尽管内在清除率值存在较大差异，但表观口服清除率和内在肝清除率处于相似范围。仅五只动物中的三只，前一项清除率估计在非妊娠状态下较低。全身清除率变化很小，在怀孕期间和非孕期处于相同范围。怀孕和未怀孕的恒河猴之间美托洛尔表观口服清除率和口服生物利用度的变化与孕妇中观察到的变化相似，尽管绝对值不同。
