PIP: The authors determined plasma levels of metoprolol, a widely used beta-adrenoceptor blocker, following oral administration of 100 mg to 23 women. 1/2 of this group were taking a combined estrogen-ethinyl estradiol low dose oral contraceptive (OC). Blood samples were taken before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dosing. The volunteers were supine for 8 hours, then the cannula was removed, the patients were allowed up, and the last 2 samples were obtained by venepuncture. The concentration of metoprolol in plasma was determined by a modification of the Jack and Riess method. The average age of the control group was 20.7 years compared with 20.5 for the pill group. The difference in AUC between the 2 groups was significant at the P=0.05 level (metoprolol control-662; metoprolol OC-1051). No other parameters displayed statistical significance. Metoprolol plasma concentrations were higher in women taking the pill and the difference was significant. The AUC increase with no change in t 1/2 is consistent with an inhibitory effect of the pill on hepatic microsomal oxidase. Hepatic drug elimination is determined mainly by the activity of the drug metabolizing enzymes and hepatic blood flow. Drugs such as metoprolol with a high extraction ratio do not show changes in clearance and 1/2-life if hepatic enzymes are inhibited. Smoking is known to induce drug metabolizing enzymes and this must be considered. The clinical importance of the interaction between beta-adrenoceptor blockers and OCs is probably small since the overlap between the 2 groups is small. These results, however, suggest that beta-adrenoceptor blocker metabolism may be influenced by the effects of other drugs which inhibit microsomal enzyme activity. Presently, there is research underway to examine the effects of OCs on other beta-adrenoceptor blockers.