Vanderveen R P, Jirak J L, Peters G R, Cox S R, Bombardt P A
College of Pharmacy, Oregon State University, Oregon Health Sciences University Hospital, Portland 97201.
Clin Pharm. 1991 Jul;10(7):539-43.
The effect of orally administered ranitidine on the pharmacokinetic properties of orally and intravenously administered triazolam was determined. Twelve healthy males with a mean age of 35 years were enrolled in this four-way, randomized, crossover study. Each subject received a total of four treatments, each separated by one week. The treatments consisted of (1) one orally administered 0.25-mg triazolam tablet after treatment with ranitidine; (2) one orally administered 0.25-mg triazolam tablet, with no ranitidine pretreatment; (3) a 0.25-mg intravenous dose of triazolam after treatment with ranitidine; and (4) a 0.25-mg intravenous dose of triazolam, with no ranitidine pretreatment. Ranitidine pretreatment consisted of five 150-mg oral doses (as the hydrochloride salt) given every 12 hours; the last dose was given two hours before triazolam was administered. Blood samples were taken at intervals up to 12 hours after triazolam treatment. Serum triazolam concentrations were measured by modified high-performance liquid chromatography, and pharmacokinetic values were calculated. Pretreatment with ranitidine had no effect on the disposition of intravenously administered triazolam but significantly increased the area under the serum drug concentration-time curve of oral triazolam. Ranitidine pretreatment had no effect on triazolam's terminal elimination rate constant or on the time to reach maximum serum triazolam concentration. Ranitidine pretreatment increased the systemic availability of triazolam by increasing its absorption.
本研究旨在确定口服雷尼替丁对口服和静脉注射三唑仑药代动力学特性的影响。12名平均年龄为35岁的健康男性参与了这项四组随机交叉研究。每位受试者共接受四种治疗，每次治疗间隔一周。治疗方案包括：（1）雷尼替丁治疗后口服一片0.25毫克三唑仑片；（2）未进行雷尼替丁预处理直接口服一片0.25毫克三唑仑片；（3）雷尼替丁治疗后静脉注射0.25毫克三唑仑；（4）未进行雷尼替丁预处理直接静脉注射0.25毫克三唑仑。雷尼替丁预处理方案为每12小时口服5次150毫克剂量（盐酸盐形式）；最后一剂在给予三唑仑前两小时服用。在三唑仑治疗后长达12小时的时间段内间隔采集血样。采用改良高效液相色谱法测定血清三唑仑浓度，并计算药代动力学值。雷尼替丁预处理对静脉注射三唑仑的处置无影响，但显著增加了口服三唑仑血清药物浓度-时间曲线下面积。雷尼替丁预处理对三唑仑的终末消除速率常数及达到血清三唑仑最大浓度的时间无影响。雷尼替丁预处理通过增加三唑仑的吸收提高了其全身生物利用度。
