Cavanaugh J H, Karol M D
Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
J Clin Pharmacol. 1996 Nov;36(11):1064-71. doi: 10.1177/009127009603601110.
In a recently reported case, administration of omeprazole, a "proton pump" inhibitor, was temporally associated with the clinical relapse of pemphigus in a 44-year-old woman whose condition had been stabilized with a fixed dose of prednisone, suggesting the possibility of a drug interaction. This placebo-controlled, randomized, double-blind, three-period crossover study was conducted to evaluate and compare the pharmacokinetics of prednisolone after a single dose of prednisone given during multi-dose administration of lansoprazole or omeprazole. Lansoprazole (30 mg), omeprazole (40 mg), or placebo was administered once daily under fasted conditions for 7 days to healthy male volunteers. On the seventh day, a single dose of prednisone (40 mg) was administered concomitantly with the study medication, and plasma prednisolone concentrations were measured by high-performance liquid chromatography for 24 hours thereafter. Two weeks separated the first doses of each study period. Eighteen volunteers entered the study; pharmacokinetic data were evaluable for 15 participants. Safety data were evaluable for 16 participants in the lansoprazole/prednisone group; 17 in the omeprazole/ prednisone group; and 17 in the placebo/prednisone group. The pharmacokinetic parameters for prednisolone, including the maximum observed plasma concentration (Cmax), time to maximum plasma concentration (tmax), terminal-phase half-life (t1/2), and area under the concentration-time curve, were comparable for the three regimens. Adverse events (AEs) rated as possibly or probably drug related were reported by 50%, 24%, and 47% for subjects in the lansoprazole, omeprazole, and placebo treatment groups, respectively. Headache was the most common drug-related AE. No serious AEs were reported, and no subject withdrew from the study because of an AE. Concomitant administration of lansoprazole or omeprazole does not affect the absorption, biotransformation, or disposition of a single dose of prednisone. All three treatment regimens were well tolerated.
在最近报道的一例病例中，一名44岁女性的天疱疮病情已通过固定剂量的泼尼松稳定下来，但使用“质子泵”抑制剂奥美拉唑后，病情出现临床复发，提示存在药物相互作用的可能性。本项安慰剂对照、随机、双盲、三阶段交叉研究旨在评估和比较在兰索拉唑或奥美拉唑多剂量给药期间给予单剂量泼尼松后泼尼松龙的药代动力学。在禁食条件下，每天一次给健康男性志愿者服用兰索拉唑（30毫克）、奥美拉唑（40毫克）或安慰剂，持续7天。在第7天，与研究药物同时给予单剂量泼尼松（40毫克），此后24小时通过高效液相色谱法测定血浆泼尼松龙浓度。每个研究阶段的首次给药间隔两周。18名志愿者进入研究；15名参与者的药代动力学数据可评估。兰索拉唑/泼尼松组16名参与者、奥美拉唑/泼尼松组17名参与者和安慰剂/泼尼松组17名参与者的安全性数据可评估。三种治疗方案的泼尼松龙药代动力学参数，包括最大观察血浆浓度（Cmax）、达到最大血浆浓度的时间（tmax）、终末相半衰期（t1/2）和浓度-时间曲线下面积，具有可比性。兰索拉唑、奥美拉唑和安慰剂治疗组的受试者分别有50%、24%和47%报告了可能或很可能与药物相关的不良事件（AE）。头痛是最常见的与药物相关的AE。未报告严重AE，也没有受试者因AE退出研究。同时服用兰索拉唑或奥美拉唑不影响单剂量泼尼松的吸收、生物转化或处置。所有三种治疗方案耐受性良好。
