Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers.

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 i...

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Publicado en:European Journal of Clinical Pharmacology Vol. 64; no. 5; pp. 503 - 510
Autores principales: Niioka T, Miura M, Uno T, Yasui-Furukori N, Hayakari M, Tateishi T, Suzuki T
Formato: clinical trial research Journal Article
Publicado: Springer Nature May2008
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2008
      vid: 64
      iid: 5
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      pub: Springer Nature
      place: New York, New York
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        2009880446
        10.1007/s00228-007-0455-5
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        atl: Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers.
      aug:
        au:
          Niioka T
          Miura M
          Uno T
          Yasui-Furukori N
          Hayakari M
          Tateishi T
          Suzuki T
        affil: Department of Pharmacy, Hirosaki University Hospital, Aomori, Japan.
      sug:
        subj:
          Proton Pump Inhibitors Pharmacokinetics
          Proton Pump Inhibitors
          Sulfur Compounds Pharmacokinetics
          Sulfur Compounds
          Adult
          Amines Pharmacodynamics
          Chemistry
          Clarithromycin Pharmacodynamics
          Crossover Design
          Double-Blind Studies
          Female
          Genotype
          Male
          Models, Biological
          Oxidoreductases Antagonists and Inhibitors
          Oxidoreductases Metabolism
          Pharmacokinetics
          Proton Pump Inhibitors Blood
          Sulfur Compounds Blood
          Time
          Human
          Adult: 19-44 years
          Female
          Male
      ab: 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 [Formula: see text] (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.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        Journal Article
      ougenre: Article
    language: English
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