Ette E I, Brown-Awala E A, Essien E E
Department of Clinical Pharmacy and Biopharmacy, School of Pharmacy, College of Medicine, University of Lagos, Nigeria.
J Clin Pharmacol. 1987 Oct;27(10):813-6. doi: 10.1002/j.1552-4604.1987.tb03002.x.
A controlled study was carried out in ten healthy, male volunteers (randomly distributed into control and test groups of five subjects each) to determine the effect of low-dose cimetidine on chloroquine elimination. The control group subjects received two tablets of chloroquine sulfate (300-mg base) only, while the test group subjects took 400-mg cimetidine at bedtime for four days prior to chloroquine (two tablets of chloroquine sulfate) administration and throughout the duration of the study. Blood samples, 5 mL, were collected periodically after chloroquine administration. The samples were assayed for chloroquine and monodesethylchloroquine using a combination of thin-layer chromatography and spectrophotometry. Wilcoxon's test for unpaired data at P less than .05 was used to determine if there was any significant difference in the elimination of chloroquine in the test group when compared with the control group. The apparent oral clearance rate of chloroquine was reduced from 0.49 +/- 0.04 L/d/kg in the control group to 0.23 +/- 0.02 L/d/kg in the test group, and the elimination half-life was prolonged from 3.11 days in the control group to 4.62 days in the test group. There was a 47.04% reduction in the AUC0-7d of monodesethylchloroquine, the major metabolite of chloroquine, in the test group when compared with the control group. The apparent volume of distribution at steady state was increased from 0.46 +/- 0.07 L/kg in the control group to 0.72 +/- 0.10 L/kg in the test group. All these changes were statistically significant. The conclusion is that cimetidine impairs the elimination of chloroquine in healthy subjects.
对10名健康男性志愿者进行了一项对照研究（随机分为对照组和试验组，每组5名受试者），以确定低剂量西咪替丁对氯喹消除的影响。对照组受试者仅服用两片硫酸氯喹（300毫克碱基），而试验组受试者在服用氯喹（两片硫酸氯喹）前四天及整个研究期间，每晚服用400毫克西咪替丁。服用氯喹后定期采集5毫升血样。使用薄层色谱法和分光光度法联合测定血样中的氯喹和单去乙基氯喹。采用Wilcoxon非配对数据检验（P小于0.05）来确定试验组与对照组相比，氯喹消除是否存在显著差异。氯喹的表观口服清除率从对照组的0.49±0.04升/天/千克降至试验组的0.23±0.02升/天/千克，消除半衰期从对照组的3.11天延长至试验组的4.62天。试验组中氯喹的主要代谢产物单去乙基氯喹的AUC0 - 7d与对照组相比降低了47.04%。稳态时的表观分布容积从对照组的0.46±0.07升/千克增加至试验组的0.72±0.10升/千克。所有这些变化均具有统计学意义。结论是西咪替丁会损害健康受试者体内氯喹的消除。
