Interaction between oral propranolol and hydralazine.

Seven healthy subjects were given oral propranolol (1 mg/kg) alone or in combination with hydralazine 25, 50, or 100 mg on separate occasions. Hydralazine induced variable increases in the peak concentrations (p less than 0.05) and in the area under the propranolol concentration: time curves (p less than 0.02) without change in the recovery of 14 C-propranolol/metabolites in urine or in the systemic clearance of propranolol; i.e., oral hydralazine enhanced the systemic availability of propranolol by alteration of "first-pass" (hepatic) clearance. The results indicate the possibility of change in presystemic clearance without reciprocal change in systemic clearance and also suggest that propranolol or any other high-clearance drug should be administered in fixed relationship to hydralazine and other drugs capable of altering "first-pass" hepatic extraction (either due to alteration in splanchnic blood flow or competitive inhibition of metabolism) if large variations in plasma concentrations are to be avoided.