Urinary 6 beta-hydroxycortisol and D-glucaric acid excretion rates are not affected by lansoprazole treatment.
Lansoprazole has been shown to induce cytochrome P450 1A (CYP1A) and CYP3A enzymes in human hepatocytes in vitro. In this study, urinary excretion of 6 beta-hydroxycortisol (6 beta-OHF) and D-glucaric acid (D-GA) were used to investigate the potential enzyme-inducing property of lansoprazole in vivo. Twenty-four healthy female volunteers (aged 19-35 years), who were taking oral contraceptives containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel, were randomized in a cross-over design for the treatment with either 60 mg lansoprazole or placebo once daily during 2 subsequent menstrual cycles. Urinary excretion rates of 6 beta-OHF and D-GA were measured at days 14 and 21 of the menstrual cycles. Median pretreatment urinary excretion of 6 beta-OHF (212 and 218 micrograms/d, n = 24) and D-GA (20.1 and 32.7 mumol/d) did not significantly differ. Upon treatment median excretion of 6 beta-OHF was 255 and 241 micrograms/d (n = 23), and that of D-GA was 25.5 and 33.8 mumol/d, respectively. Thus, the relatively high dose of 60 mg/d lansoprazole failed to statistically significantly alter urinary excretion of 6 beta-OHF and D-GA, indicating that therapeutic doses of lansoprazole might not exhibit a phenobarbital-like induction in vivo.
Rost
K L
KL
Institute of Clinical Pharmacology, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
Mansmann
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Roots
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D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D005937:Glucaric Acid / Q000652:urine*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D064747:Lansoprazole; D016912:Levonorgestrel / Q000494:pharmacology; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D010919:Placebos; D045167:Progesterone Congeners / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D003277:Contraceptives, Oral, Combined; D004791:Enzyme Inhibitors; D045166:Estradiol Congeners; D010919:Placebos; D045167:Progesterone Congeners; D064747:Lansoprazole; D004997:Ethinyl Estradiol; C001380:6 beta-hydroxycortisol; D016912:Levonorgestrel; D003577:Cytochrome P-450 Enzyme System; D009853:Omeprazole; D005937:Glucaric Acid; D006854:Hydrocortisone