Interaction between oral propranolol and hydralazine

Abstract

Seven healthy [human] subjects were given oral propranolol [.beta.-adrenoceptor blocker] (1 mg/kg) alone or in combination with hydralazine [vasodilator] 25, 50 or 100 mg on separate occasions. Hydralazine induced variable increases in the peak concentrations (P < 0.05) and in the area under the propranolol concentration: time curves (P < 0.02) without change in the recovery of 14C-propranolol/metabolites in urine or in the systemic clearance of propranolol; i.e., oral hydralazine enhanced the systemic availability of propranolol by alteration of 1st-pass (hepatic) clearance. The possibility of change in presystemic clearance without reciprocal change in systemic clearance is indicated; propranolol or any other high-clearance drug probably should be administered in fixed relationship to hydralazine and other drugs capable of altering 1st-pass hepatic extraction (due to alteration in splanchnic blood flow or competitive inhibition of metabolism) if large variations in plasma concentrations are to be avoided.