Carter B L, Garnett W R, Pellock J M, Stratton M A, Howell J R
Ther Drug Monit. 1981;3(4):333-40. doi: 10.1097/00007691-198104000-00003.
Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone on two separate occasions and phenytoin plus each of the three antacids on three other occasions. Each antacid was administered as 160 mEq at 1 and 3 hr after each meal and at bedtime on the day phenytoin was given. The mean area under the curve (AUC) was significantly decreased by AMH (p less than 0.005) and CC (p less than 0.05). AHMT had a similar trend but did not reach statistical significance (p = 0.1). Large inter- and intrasubject variability in AUC was observed when phenytoin was administered alone. In two subjects, cumulative urinary 5-(4-hydroxyphenyl)-5-phenylhydantoin at 72 hr (HPPH72) was determined. The amount of HPPH recovered had similar trends as the AUC with antacid treatments but not the same magnitude. In this study, antacids altered not only the extent of absorption but also appeared to alter the rate of absorption. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin.
采用随机交叉设计对8名受试者进行研究，以确定氢氧化铝镁（AMH）、碳酸钙（CC）和氢氧化铝硅酸镁（AHMT）对口服单剂量600毫克苯妥英生物利用度的影响。每名受试者在两个不同的时间段单独服用苯妥英，在另外三个时间段服用苯妥英加三种抗酸剂中的每一种。在服用苯妥英当天，每种抗酸剂在每餐饭后1小时和3小时以及睡前各服用160毫当量。AMH（p<0.005）和CC（p<0.05）使曲线下平均面积（AUC）显著降低。AHMT有类似趋势，但未达到统计学意义（p = 0.1）。单独服用苯妥英时，观察到受试者之间和受试者内部的AUC存在较大变异性。对两名受试者测定了72小时时的累积尿5-（4-羟基苯基）-5-苯基乙内酰脲（HPPH72）。回收的HPPH量与抗酸剂治疗时的AUC有类似趋势，但幅度不同。在本研究中，抗酸剂不仅改变了吸收程度，而且似乎还改变了吸收速率。以消化性溃疡治疗方案服用的抗酸剂可能会降低单剂量苯妥英的AUC。应告诫患者不要同时使用抗酸剂和苯妥英。
