Hydralazine Pharmacokinetics and Interaction with Food: An Evaluation of the Dog as an Animal Model

Abstract

The intravenous and oral dose-dependent pharmacokinetics of hydralazine and the effect of concurrent administration of food with hydralazine in dogs were evaluated for comparison with published human data. Four dogs were given intravenous and oral doses of hydralazine at 0.25, 1.0, 2.5, and 4.0 mg/kg. In addition, the oral 2.5 mg/kg dose was given with a meal. Blood samples were collected at appropriate intervals and analyzed for hydralazine. Pharmacokinetic analysis showed that AUC_oral/ dose (5552 to 13218 mg-min/ml) and F (0.36 to 0.77) increased significantly with dose, indicating saturation of first-pass metabolism, as is seen in humans. Total-body clearance (70 ml/min/kg) and steady-state volume of distribution (9 L/kg) were similar to human values. The bioavailability of hydralazine in the dog was decreased by 63% when the dose was given with a meal, which is comparable to some human data. It was concluded that the dog may be a useful model in which to study mechanisms of the hydralazine-food interaction.