Effects of hydralazine, nitroglycerin, and food on estimated hepatic blood flow

Abstract

Several recent studies have shown that hydralazine and nitroglycerin may increase the apparent oral bioavailability of high-clearance drugs. It has been postulated that the mechanism responsible may be a vasodilator-induced transient increase in hepatic blood flow with an associated reduction in first-pass metabolism. To test this hypothesis, we examined the effect of hydralazine (25 mg) and sublingual nitroglycerin (2 doses of 0.6 mg separated by 30 minutes) on indocyanine green (ICG) blood clearance (ClB). Forty minutes after the start of nitroglycerin therapy, ICG ClB fell from a baseline of 648 +/- 98 to 607 +/- 151 ml/min, and was further decreased to 578 +/- 98 ml/min 80 minutes after dosing. Hydralazine induced no consistent effect on ICG ClB. ICG ClB was 744 +/- 376, 721 +/- 218, and 763 +/- 195 ml/min at baseline, 40 minutes, and 80 minutes after dosing. As a positive control, ICG ClB was assessed after a high-protein meal. After this meal, ICG ClB increased from 656 +/- 107 to 811 +/- 141 and 801 +/- 132 ml/min at 40 and 80 minutes after dosing. These data suggest that one or more mechanism(s) other than changes in hepatic blood flow are involved in the vasodilator-induced increase in the apparent oral bioavailability of high-clearance drugs.