Semple H A, Tam Y K, Coutts R T
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Pharm Res. 1990 Mar;7(3):274-9. doi: 10.1023/a:1015830330231.
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 AUCoral/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.
评估了肼屈嗪的静脉注射和口服剂量依赖性药代动力学以及在犬中肼屈嗪与食物同时给药的效果，以便与已发表的人体数据进行比较。给四只犬静脉注射和口服剂量分别为0.25、1.0、2.5和4.0mg/kg的肼屈嗪。此外，口服2.5mg/kg剂量的肼屈嗪时同时给予一餐食物。在适当的时间间隔采集血样并分析其中的肼屈嗪。药代动力学分析表明，AUCoral/剂量（5552至13218mg·min/ml）和F（0.36至0.77）随剂量显著增加，表明首过代谢饱和，这与人类情况相似。总体清除率（70ml/min/kg）和稳态分布容积（9L/kg）与人体值相似。当与食物同时给药时，犬中肼屈嗪的生物利用度降低了63%，这与一些人体数据相当。得出的结论是，犬可能是研究肼屈嗪-食物相互作用机制的有用模型。
