Amsden G W, Goss T F, Harrison N J, D'Andrea D T, Schentag J J
Clinical Drug Research Center, Saint Vincent Hospital, Worcester, Massachusetts 01604.
J Clin Pharmacol. 1994 Dec;34(12):1191-8. doi: 10.1002/j.1552-4604.1994.tb04731.x.
A four-way crossover pilot study was conducted to compare the pharmacodynamic response of intermittent famotidine (20 mg every 12 hr) to continuous infusions of cimetidine (1200 mg/24 hr), ranitidine (150 mg/24 hr), and famotidine (40 mg/24 hr) in six normal male volunteers. Intragastric pH was monitored continuously for 24 hours. Comparisons included percent time during the 24-hour period that gastric pH was greater than pH 4.0, and pH 5.0, and also for the steady-state period of each regimen (12-24 hr). Although no statistically significant difference was observed for any of these comparisons, a clinically relevant trend was observed. In crossover experiments, famotidine intermittent infusions provided gastric pH readings above 4.0 and 5.0 for a longer duration than any of the continuous infusion regimens. Famotidine intermittent infusion regimens (20 mg every 12 hr) are at least equivalent to continuous infusions of cimetidine, ranitidine, and famotidine. Based on these findings, comparative studies in an appropriate critical care population would be beneficial, but any such studies must use a crossover design because of the even higher degree of intersubject variance in pH control. For this reason, the normal volunteer crossover model used here may provide important comparative information for the various regimens used in suppression of gastric acidity.
进行了一项四交叉试点研究，以比较六名正常男性志愿者中间歇性法莫替丁（每12小时20毫克）与西咪替丁（1200毫克/24小时）、雷尼替丁（150毫克/24小时）和法莫替丁（40毫克/24小时）持续输注的药效学反应。连续24小时监测胃内pH值。比较内容包括24小时期间胃pH值大于4.0和5.0的时间百分比，以及每种方案的稳态期（12 - 24小时）。尽管在这些比较中未观察到统计学上的显著差异，但观察到了临床相关趋势。在交叉实验中，间歇性输注法莫替丁使胃pH值高于4.0和5.0的持续时间比任何持续输注方案都长。法莫替丁间歇性输注方案（每12小时20毫克）至少等同于西咪替丁、雷尼替丁和法莫替丁的持续输注。基于这些发现，在适当的重症监护人群中进行比较研究将是有益的，但由于pH值控制中受试者间差异程度更高，任何此类研究都必须采用交叉设计。因此，这里使用的正常志愿者交叉模型可能为用于抑制胃酸的各种方案提供重要的比较信息。
