Shepherd A M, Irvine N A, Ludden T M
Clin Pharmacol Ther. 1984 Jul;36(1):14-8. doi: 10.1038/clpt.1984.131.
A study with a nonspecific hydralazine assay reported that food increased hydralazine concentrations in plasma. We used a specific HPLC hydralazine assay to determine the effect of food on hydralazine blood levels and hemodynamic responses after oral hydralazine. Six subjects with uncomplicated essential hypertension were given 1 mg/kg hydralazine solution orally on two occasions at least 3 days apart. On 1 study day subjects fasted and on the other they were given a standard meal 45 min before hydralazine. Mean arterial pressure and heart rate were monitored for 2 hr before and for 4 hr after hydralazine and frequent venous blood samples were drawn for hydralazine assay. Hepatic blood flow was estimated by determination of indocyanine green clearance before food, after food, and 30 min after hydralazine. Peak blood hydralazine concentrations fell in all (46.2% +/- 11.5%; means +/- SE) and areas under the blood hydralazine concentration/time curves fell (45.7% +/- 9.5%) after food. This could not be explained by changes in liver blood flow. Food-related reductions in blood levels of hydralazine were associated with reduced vasodepressor effects (41.5% +/- 5.6%). It is possible that food increases intravascular conversion of hydralazine to hydralazine pyruvic acid hydrazone. The reduction in vasodepressor response suggests that patients with hypertension should take hydralazine at a fixed time in relation to meals.
一项使用非特异性肼屈嗪检测方法的研究报告称，食物会增加血浆中肼屈嗪的浓度。我们采用特异性高效液相色谱法检测肼屈嗪，以确定食物对口服肼屈嗪后肼屈嗪血药浓度及血流动力学反应的影响。6例无并发症的原发性高血压患者，至少间隔3天口服1mg/kg肼屈嗪溶液2次。在1个研究日，受试者禁食；在另一个研究日，受试者在服用肼屈嗪前45分钟进食标准餐。在服用肼屈嗪前2小时和服用后4小时监测平均动脉压和心率，并频繁采集静脉血样检测肼屈嗪。分别在进食前、进食后以及服用肼屈嗪后30分钟，通过测定吲哚菁绿清除率估算肝血流量。进食后，所有受试者的肼屈嗪血药浓度峰值均下降（46.2%±11.5%；均值±标准误），肼屈嗪血药浓度/时间曲线下面积下降（45.7%±9.5%）。这无法用肝血流量的变化来解释。食物导致的肼屈嗪血药浓度降低与血管减压作用减弱有关（41.5%±5.6%）。食物可能会增加肼屈嗪在血管内转化为丙酮酸腙的过程。血管减压反应减弱表明高血压患者应在与进餐相关的固定时间服用肼屈嗪。
