title: Urinary 6 beta-hydroxycortisol and D-glucaric acid excretion rates are not affected by lansoprazole treatment.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: K L
authors.initials: KL
authors.lastname: Rost
authors.forename: U
authors.initials: U
authors.lastname: Mansmann
authors.forename: I
authors.initials: I
authors.lastname: Roots
mesh_terms: 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
chemical_list: 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