The rhesus monkey as a model for studies of pregnancy induced changes in metoprolol metabolism

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.