Pregnancy-induced increase in metoprolol metabolism

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.