Five women who developed hypertension during pregnancy received metoprolol, 10 mg iv; 3 days later they received metoprolol, 100 mg by mouth. Blood and urine samples were collected after each dose. The same procedure was repeated 3 to 6 months after delivery. The apparent oral clearance of metoprolol during pregnancy exceeded that after pregnancy by a factor of 2 to 13. As a result, after oral dosing the peak plasma concentrations during pregnancy were only 12% to 55% those after delivery, and the plasma AUCs were reduced to the same extent. Oral bioavailability increased by a factor of 1.3 to 3.7 after pregnancy. Systemic clearance after pregnancy was 26% to 97% that during pregnancy, but this difference was not significant. Metoprolol plasma protein binding was the same on both study occasions. Our data cannot be explained by a change in gastrointestinal absorption, because the urinary recovery of metoprolol and its metabolites was slightly higher during pregnancy. It is concluded that the greater metoprolol clearance during pregnancy results from increased hepatic metabolism of the drug.

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.

In an open, controlled trial, treatment with a combination of metoprolol and hydralazine was compared with non-pharmacological management of mild and moderate hypertension in pregnancy. One hundred and sixty-one women participated in the study. The drug-treated group showed significantly better blood pressure control than the group not given antihypertensives. Induction of labor before term, because of maternal or fetal complications, was somewhat more frequent in the control group. Nine women in the treatment group and 5 in the control group developed albuminuria. Three infants in the drug-treated group died perinatally, and one in the control group. The outcome for the newborns was similar in both groups concerning birth weight, head circumference and Apgar score and in the frequencies of respiratory distress, bradycardia and hypoglycemia. The better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery, but treatment does not seem to be mandatory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy.