title: Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.
abstract: OBJECTIVE
  To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects.
  
  
  METHODS
  Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined.
  
  
  RESULTS
  The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes.
  
  
  CONCLUSIONS
  Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.
authors.affiliation: Clinical Development Institute, Banyu Pharmaceutical Co. Ltd., Kitanomaru Square, 1-13-12, Kudan-Kita, Chiyoda-ku, Tokyo, 102-8667, Japan. toshio_yasumori@merck.com
authors.forename: T
authors.initials: T
authors.lastname: Yasumori
authors.forename: H
authors.initials: H
authors.lastname: Narita
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Takubo
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: M
authors.initials: M
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Okuyama
authors.forename: G
authors.initials: G
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Ochiai
authors.forename: A
authors.initials: A
authors.lastname: Kano
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000378:metabolism / Q000493:pharmacokinetics*; D010597:Pharmacogenetics
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D018120:Finasteride; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole