Increased oral clearance of metoprolol in pregnancy.

The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20-40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smaller during (mean 262 nmol/1 X h) than after (mean 1298 nmol/1 X h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4 times higher during (362 ml X kg-1 body-weight X min-1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.