Pharmacoepidemiologic investigation of a clonazepam-valproic acid interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.

Non-linear Mixed Effects Modeling (NONMEM) was used to estimate the effects of clonazepam-valproic acid interaction on clearance values using 576 serum levels collected from 317 pediatric and adult epileptic patients (age range, 0.3-32.6 years) during their clinical routine care. Patients received t...

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Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 28; no. 6; pp. 497 - 505
Autores principales: Yukawa E, Nonaka T, Yukawa M, Higuchi S, Koruda T, Goto Y
Formato: equations & formulas research tables/charts Journal Article
Publicado: Wiley-Blackwell Dec2003
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2003
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      pub: Wiley-Blackwell
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        atl: Pharmacoepidemiologic investigation of a clonazepam-valproic acid interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.
      aug:
        au:
          Yukawa E
          Nonaka T
          Yukawa M
          Higuchi S
          Koruda T
          Goto Y
        affil: Laboratory of Evidence-Based Pharmacotherapy, College of Pharmaceutical Sciences, Daiichi University, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan; yukawa@daiichi-cps.ac.jp
      sug:
        subj:
          Clonazepam Pharmacokinetics
          Drug Interactions Evaluation
          Valproic Acid Pharmacokinetics
          Adult
          Child
          Clonazepam Pharmacodynamics
          Descriptive Statistics
          Female
          Funding Source
          Infant
          Japan
          Male
          Models, Theoretical
          Retrospective Design
          Valproic Acid Pharmacodynamics
          Human
          Adult: 19-44 years
          Child: 6-12 years
          Infant: 1-23 months
          Female
          Male
      ab: Non-linear Mixed Effects Modeling (NONMEM) was used to estimate the effects of clonazepam-valproic acid interaction on clearance values using 576 serum levels collected from 317 pediatric and adult epileptic patients (age range, 0.3-32.6 years) during their clinical routine care. Patients received the administration of clonazepam and/or valproic acid. The final model describing clonazepam clearance was CL = 144.0 TBW-0.172 1.14VPA, where CL is total body clearance (mL/kg/h); TBW is total body weight (kg); VPA = 1 for concomitant administration of valproic acid and VPA = zero otherwise. The final model describing valproic acid clearance was CL (mL/kg/h) = 17.2 TBW-0.264 DOSE0.159 0.821CZP 0.896GEN, where DOSE is the daily dose of valproic acid (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise; GEN = 1 for female and GEN = zero otherwise. Concomitant administration of clonazepam and valproic acid resulted in a 14% increase in clonazepam clearance, and a 17.9% decrease in valproic acid clearance.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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