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Individual dosage regimen based on population pharmacokinetics and genotyping of drug metabolizing enzymes

Research Project

Project/Area Number 09672323
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HASHIMOTO Yukiya  Graduate School of Medicine, Kyoto University Associate Professor, 医学研究科, 助教授 (90228429)

Co-Investigator(Kenkyū-buntansha) OKUDA Masahiro  Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (70252426)
YANO Ikuko  Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (50273446)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsphenytoin / population pharmacokinetics / CYP2C9 / CYP2C19 / genetic polymorphism / non-linear pharmacokinetics / p450 / drug metabolism
Research Abstract

We have estimated the population pharmacokinetic parameters of phenytoin in Japanese patients with epilepsy (Biol. Pharm. Bull., 19, 444, 1996), and examined the effect of cytochrome P450 (CYP) 2C9/19 polymorphisms on the pharmacokinetics of phenytoin (Clin. Pharmacol. Ther., 62, 287, 1997). In this study, we evaluated the phenytoin dosage regimen based on the simple polymerase chain reaction-based genetic test of CYP2C isozymes. The population pharmacokinetic parameters without the information of CYP2C genotypes failed to predict the serum phenytoin concentration in patients with the mutation in CYP2C9 (Ile^<359>*Leu). In contrast, the genotyping of CYP2C9/19 in individual patients was useful in determining which patients are at risk for drug intoxication. In addition, the precision of the predicted serum phenytoin concentrations was improved by the baysian analysis based on the population pharmacokinetic parameters involving the polymorphism of CYP2C subfamily. The genetic test for the CYP2C isozymes will be useful in designing the dosage of phenytoin.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 橋本征也: "母集団速度論に基づく薬物体内動態と薬効の解析" 薬物動態. 12. 401-406 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小谷敦子: "フェニトインの新規母集団パラメータに基づくベイジアン解析法の評価" 病院薬学. 23. 512-518 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Odani, Atsuko: "Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy." Clin. Pharmacol. Ther.62. 287-292 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sasa, Hiroaki: "Hepatic extraction of tacrolimus in rats with experimental liver diaeases." Biol. Pharm. Bull.21. 610-614 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hashimoto, Yukiya: "Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats." Pharm.Res.15. 1609-1613 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 橋本征也: "CYP2C サブファミリーの遺伝子診断情報に基づくフェニトイン個別投与設計法の評価" 臨床薬理. 30. 9-16 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yukiya Hashimoto: "Pharmacokinetic and pharmacodynamic analysis based on population approach." Xenobio.Metabol.Dispos.14. 401-406 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuko Odani et al.: "Evaluation of the bayesian individual dosage regimen based on the new population pharmacokinetic parameters of phentyoin." Jap.J.Hosp.Pharm.23. 512-518 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuko Odani et al.: "Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy." Clin.Pharmacol.Ther.62. 287-292 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroaki Sasa et al.: "Hepatic extraction of tacrolimus in rats with experimental liver deseases." Biol.Pharm.Bull.21. 610-614 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yukiya Hashimoto et al.: "Effects of intestinal and hepatic metabolism on the bioavailability of tracrolimus in rats." Pharm.Res.15. 1609-1613 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yukiya Hashimoto et al.: "Evaluation of individual dosage regimen based on genotyping of the CYP2C subfamily." Jap.J.Clin.Pharmacol.Ther.30. 9-16 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai,Junya: "Effect of intracellular α-ketoglutarate ria p-aminohippurate/dicarboxylate exchange in OK kidney epithelial cells." J.Pharmacol.Exp.Thev.285・2. 422-427 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura,Tsutomu: "Effect of fosfomicin and imipenem/cilastatin on nephrotoxicity and renal excretion of vancomycin in rats." Pharm.Res.15・5. 734-738 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sasa,Hiroaki: "Hepatic extraction of tacrolimus in rats with experimental liver diseases." Biol.Pharm.Bull.21・6. 610-614 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaguchi,Masayuki: "Effect of neutral endopeptidase inhibition on the renal clearance and natriuresis of atrial natriuretic peptide in perfused rat kidney." Pharm.Res.15・9. 1499-1502 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hashimoto,Yukiya: "Effect of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats." Pharm.Res.15・10. 1609-1613 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 橋本征也: "CYP2Cサブファミリーの遺伝子診断に基づくPhenytion個別投与設計法の評価" 臨床薬理. 30・1. 9-16 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 橋本征也: "母集団薬物速度論に基づく薬物体内動態と薬効の解析" 薬物動態. 12・4. 401-406 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Odani.: "Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokine Tics of phenytoin in Japanese patients with pilepsy." Clin.Pharmacol.Ther.62・3. 287-292 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小谷 敦子: "フェニトインの新規母集団パラメータに基づくベイジアン解析法の評価" 病院薬学. 23・6. 512-518 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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