Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers

Jae Wook Ko, In Jin Jang, Jae Gook Shin, Sang Keon Nam, Sang Goo Shin, David A. Flockhart

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 times 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 μg · h/mL in white extensive metabolizers, 7.01 ± 0.72 μg · hr/mL in Korean extensive metabolizers, and 14.34 ± 2.60 μg · 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 lansoprazole (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.

Original languageEnglish (US)
Pages (from-to)606-614
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume65
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

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Lansoprazole
Theophylline
Pharmacokinetics
Cytochrome P-450 CYP1A2
Proton Pump Inhibitors
Area Under Curve
Gastroesophageal Reflux
Cross-Over Studies
Multicenter Studies
Cytochrome P-450 CYP2C19
Stomach
Healthy Volunteers
Genotype
Liver
Population

ASJC Scopus subject areas

  • Pharmacology

Cite this

Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers. / Ko, Jae Wook; Jang, In Jin; Shin, Jae Gook; Nam, Sang Keon; Shin, Sang Goo; Flockhart, David A.

In: Clinical Pharmacology and Therapeutics, Vol. 65, No. 6, 1999, p. 606-614.

Research output: Contribution to journalArticle

Ko, Jae Wook ; Jang, In Jin ; Shin, Jae Gook ; Nam, Sang Keon ; Shin, Sang Goo ; Flockhart, David A. / Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers. In: Clinical Pharmacology and Therapeutics. 1999 ; Vol. 65, No. 6. pp. 606-614.
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abstract = "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 times 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 μg · h/mL in white extensive metabolizers, 7.01 ± 0.72 μg · hr/mL in Korean extensive metabolizers, and 14.34 ± 2.60 μg · 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 lansoprazole (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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AU - Shin, Sang Goo

AU - Flockhart, David A.

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