Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers

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 metaboliz ers of CYP2C19 who have more than four rimes the area under the lansoprazol e plasma concentration-time curve (AUC) and constitute 12% to 23% of Asian populations. Theophylline owes a significant portion of its metabolism to C YP1A2 and can cause gastric acid reflux that calls for concurrent use of pr oton pump inhibitors, We conducted a prospective, randomized, subject-blind , multicenter crossover study of the effect of multiple high-dose oral lans oprazole (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 charac terized for CYP2C19 genotype, The study compared the pharmacokinetics of la nsoprazole and theophylline in five white extensive metabolizers, six Korea n extensive metabolizers, and seven poor metabolizers of CYP2C19, The pharm acokinetics 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 therapeut ic doses of lansoprazole have no clinically significant influence on the cl earance of theophylline, even in poor metabolizers of CYP2C19.