title: Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers.
abstract: OBJECTIVE
  The purpose of this study was to identify the common time point that gives plasma concentrations of lansoprazole enantiomers that adequately reflect the AUC of racemic lansoprazole.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, crossover study in three phases was conducted at intervals of 2 weeks. Eighteen healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single 60-mg oral dose of lansoprazole after 6 days of pretreatment, with either clarithromycin (800 mg/day), fluvoxamine (50 mg/day), or a placebo. Multiple linear regression analysis was used to identify the most informative sampling times of (R)- and (S)-lansoprazole, using one to three samples to estimate the AUC(0-infinity) of racemic lansoprazole.
  
  
  RESULTS
  The best R(2) in each prediction formula for the AUC of racemic lansoprazole using one, two, and three sampling points of (R)- and (S)-lansoprazole based on the data sets from all three pretreatment groups (n = 54) were 0.897, 0.930, and 0.929, respectively. The best prediction formula for the AUC of racemic lansoprazole, using the fewest sampling points of (R)- and (S)-lansoprazole, was AUC = 6.5 x C(3h) of (R)-lansoprazole + 13.7 x C(3h) of (S)-lansoprazole - 9,917.3 x G1 - 14,387.2 x G2 + 7,103.6 (P < 0.001), where C(3h) is the plasma concentration 3 h after administration, G1 = 1 for the homozygous extensive metabolizer (EM) and 0 for the other genotypes, G2 = 1 for the heterozygous EM and 0 for the other genotypes.
  
  
  CONCLUSIONS
  C(3h) monitoring of (R)- and (S)-lansoprazole is a useful time point to estimate the AUC of racemic lansoprazole. This method of plasma concentration monitoring at a few time points within 3 h might be more suitable for AUC estimation than CYP2C19 genotyping, particularly when lansoprazole is co-administered with CYP inhibitors.
authors.affiliation: Department of Pharmacy, Hirosaki University Hospital, Aomori, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayakari
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017291:Clarithromycin / Q000494:pharmacology; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D064748:Dexlansoprazole; D004311:Double-Blind Method; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D005838:Genotype; D006207:Half-Life; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008954:Models, Biological; D054328:Proton Pump Inhibitors / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D065692:Cytochrome P-450 CYP3A Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D017291:Clarithromycin; D016666:Fluvoxamine; D064748:Dexlansoprazole