Physiologically Based Pharmacokinetic Model of Venlafaxine Considering CYP2D6 Polymorphisms

スポンサーリンク

概要

• 論文の詳細を見る

• The aim of this study was to construct a physiologically based pharmacokinetic (PBPK) model based on the Nonlinear Mixed Effect Model (NONMEM) using venlafaxine pharmacokinetic data obtained from human subjects, and to investigate the effect of CYP2D6 polymorphisms with varying hepatic intrinsic clearance (CL_<int,h>). Eight compartments of the human body were considered in our PBPK model. CL_<int,h> was estimated to evaluate the contribution of CYP2D6 polymorphism to the first-pass effect and systematic metabolism of venlafaxine in the PBPK model. The PBPK model was confirmed to be functionally similar to a pharmacokinetic one-compartment model by frequency analysis. In addition, the influence of CL_<int,h> on gain and cut-off frequency was evaluated, because the frequency characteristics reflected the transient response of venlafaxine concentration. The results of CL_<int,h> (CYP2D6^*1/*^1, 259.7 L・hr^<-1>) and the liver-to-plasma partition coefficient (48.4) suggested that venlafaxine is sufficiently distributed and ultimately metabolized by the liver. Both CL_<int,h> in CYP2D6*1/*10 and CYP2D6^*10/*^10 could be estimated as 106 and 51 L・hr^<-1>, respectively, based on the value of CL_<int,h> in CYP2D6*!/ *1. We found that there was limited metabolic capacity of CYP2D6^*1/*^10 and CYP2D6*10/*10 in the liver compared to that of CYP2D6^*1/*^1. In conclusion, the PBPK model was a useful tool in evaluating the contribution of CYP2D6 polymorphism to the hepatic metabolism of venlafaxine.

• 社団法人日本生体医工学会の論文
• 2003-12-10

著者

• Azuma Junichi

  大阪大学 薬学研究科臨床薬効解析学分野

• Azuma Junichi

  Clinical Pharmacology And Pharmacogenomics Graduate School Of Pharmaceutical Sciences Osaka Universi

• Azuma Junichi

  Clinical Evaluation Of Medicines And Therapeutics Graduate School Of Pharmaceutical Sciences And Med

• Ohmoto Masanori

  Clinical Evaluation Of Medicines And Therapeutics Graduate School Of Pharmaceutical Sciences Osaka U

• FUKUDA Tsuyoshi

  Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka

• OHNO Masako

  Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka

• WATANABE Yuuki

  Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osak

• AKAZAWA Kenzo

  Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osak

• Akazawa Kenzo

  Department Of Bioinformatic Engineering Graduate School Of Information Science And Technology Osaka

• Watanabe Yuuki

  Department Of Bioinformatic Engineering Graduate School Of Information Science And Technology Osaka

• Fukuda Tsuyoshi

  Clinical Evaluation Of Medicines And Therapeutics Graduate School Of Pharmaceutical Sciences Osaka U

• 大本 まさのり

  Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka

• 渡邊 悠貴

  Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita

• 大野 雅子

  Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka

• FUKUDA Tsuyoshi

  Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University

関連論文

• 1 Pharmacogenomics of β-blocker Therapy in Chronic Heart Failure(New Approaches to Heart Failure-from Pharmacogenomics to Drug Development, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
• 健康成人におけるプランルカストのPKに及ぼすクラリスロマイシンの影響
• Determination of Single Nucleotide Polymorphisms in N-Acetyltransferase2 Gene Using an Electrochemical DNA Chip and an Automated DNA Detection System
• Physiologically Based Pharmacokinetic Model of Venlafaxine Considering CYP2D6 Polymorphisms
• Adrenergic β_1 Receptor Polymorphism (Ser49Gly) Is Associated with Obesity in Type II Diabetic Patients(Miscellaneous)
• OJ-155 CYP2A6 Genotypes are Important Factors for Nicotine Dependence and Withdrawal Symptoms in Smoking Cessation(Smoking-1 (H) OJ26,Oral Presentation (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)
• OE-081 Activation of STATS protects heart from myocardial injury induced by ischemia/reperfusion(Myocardial Ischemia-Reperfusion, Basic and Clinical 1 (IHD) : OE10)(Oral Presentation (English))
• 日本人における胆汁酸抱合酵素BAATの新規遺伝子多型
• 日本人における GlyAT の新規遺伝子多型
• The Frequency of Candidate Alleles for CYP2D6 Genotyping in the Japanese Population with an Additional Respect to the - 1584C to G Substitution
• The relationship between the pharmacokinetics of a new antipsychotic, aripiprazole, and CYP2D6 genetic polymorphism in healthy adult volunteers
• アリピプラゾールの日本人での薬物動態 : ^*41を含むCYP2D6遺伝子多型との関係
• Influence of Itraconazole Co-administration and CYP2D6 Genotype on the Pharmacokinetics of the New Antipsychotic ARIPIPRAZOLE
• Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males(Biopharmacy)
• Pharmacokinetic Evaluation of Anticonvulsants in a Patient with Porphyria
• Effect of Calcimimetic Agent, KRN568, on Gastrin Secretion in Healthy Subjects
• Estimating Torque-Angle Relations of Human Elbow Joint in Isovelocity Flexion Movements(Biological Engineering)
• Analysis of Signal Transmissions from Suprachiasmatic Nucleus in the Rat Brain Using Optical Recordings
• New Saturated Ferromagnetism in the Flat-Band Hubbard Model in High Electron Filling
• Properties of New Saturated Ferromagnetism in the 1D Flat-Band Hubbard Model as the Spiral State
• Existence of Saturated Ferromagnetic and Spiral States in 1D Lied-Ferrimagnetic Models away from Half-Filling
• Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population
• Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

もっと見る 閉じる

スポンサーリンク