title: The rhesus monkey as a model for studies of pregnancy induced changes in metoprolol metabolism.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynacology, University Hospital, Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Högstedt
authors.forename: B S
authors.initials: BS
authors.lastname: Lindberg
authors.forename: C G
authors.initials: CG
authors.lastname: Regårdh
authors.forename: U
authors.initials: U
authors.lastname: Moström
authors.forename: A
authors.initials: A
authors.lastname: Rane
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D008251:Macaca; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D008790:Metoprolol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008954:Models, Biological; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000378:metabolism*
chemical_list: D008790:Metoprolol