Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers

被引:15
作者
Ko, JW
Jang, IJ
Shin, JG
Nam, SK
Shin, SG
Flockhart, DA
机构
[1] Georgetown Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Washington, DC 20007 USA
[2] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul, South Korea
[3] Seoul Natl Univ Hosp, Clin Pharmacol Unit, Seoul 110744, South Korea
关键词
D O I
10.1016/S0009-9236(99)90082-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Lansoprazole is a potent gastric proton pump inhibitor that is metabolized by CYP2C19 but appears to induce the activity of hepatic microsomal CYP1A2 in a concentration-dependent manner. Because the inducing effect appears to be a dose-dependent phenomenon, it may be more important in poor metabolizers of CYP2C19 who have more than four rimes the area under the lansoprazole plasma concentration-time curve (AUC) and constitute 12% to 23% of Asian populations. Theophylline owes a significant portion of its metabolism to CYP1A2 and can cause gastric acid reflux that calls for concurrent use of proton pump inhibitors, We conducted a prospective, randomized, subject-blind, multicenter crossover study of the effect of multiple high-dose oral lansoprazole (30 mg twice a day for 7 days) on the pharmacokinetics of a single intravenous dose of theophylline (4.73 mg/kg) in healthy volunteers characterized for CYP2C19 genotype, The study compared the pharmacokinetics of lansoprazole and theophylline in five white extensive metabolizers, six Korean extensive metabolizers, and seven poor metabolizers of CYP2C19, The pharmacokinetics of lansoprazole were significantly different among groups; AUC values were 1.55 +/- 0.20 mu g.h/mL in white extensive metabolizers, 7.01 +/- 0.72 mu g.hr/mL in Korean extensive metabolizers, and 14.34 +/- 2.60 mu g.h/mL in poor metabolizers (P < .001), The administration of lansoprazole did not change intravenous theophylline clearance compared with placebo in any group, and theophylline clearance exhibited no correlation with AUC of lansoprasole (r(s) = 0.12; P > .1), These data suggest that usual therapeutic doses of lansoprazole have no clinically significant influence on the clearance of theophylline, even in poor metabolizers of CYP2C19.
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页码:606 / 614
页数:9
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