Inhibition of Human Drug Metabolizing Cytochrome P450 by Buprenorphine
スポンサーリンク
概要
- 論文の詳細を見る
The effects of buprenorphine, a powerful mixed agonist/antagonist analgesic, on several cytochrome P450 (CYP) isoform specific reactions in human liver microsomes were investigated to predict drug interaction of buprenorphine in vivo from in vitro data. The following eight CYP-catalytic reactions were used in this study:CYP1A1/2-mediated 7-ethoxyresorufin 0-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methyihydroxylation, CYP2C19-mediated S-mephenytoin 4-hydroxylation, CYP2D6-mediated bufuralol 1'-hydroxylation,.CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated testosterone 6β-hydroxylation. Buprenorphine strongly inhibited the CYP3A4- and CYP2D6-catalyzed reactions with Ki values of 14.7μM and 21.4 μM, respectively. The analgesic also weakly inhibited specific reactions catalyzed by CYP1A1/2 (Ki=132μM), CYP2B6 (Ki= 133μM), CYP2C19 (Ki=146μM), CYP2C8/9 (IC_<50>300μM), and CYP2E1 (IC_<50>300μM), but not CYP2A6 mediated pathway. In consideration of the Ki values obtained in this study and the therapeutic concentration of buprenor-phine in human plasma, buprenorphine would not be predicted to cause clinically significant interactions with other CYP-metabolized drugs.
- 公益社団法人日本薬学会の論文
- 2002-05-01
著者
-
梅原 薫
School of Pharmaceutical Sciences, University of Shizuoka
-
MIYAMOTO Gohachiro
Department of Drug Metabolism, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd.
-
Umehara K
School Of Pharmaceutical Sciences University Of Shizuoka
-
梅原 薫
School Of Pharmaceutical Sciences University Of Shizuoka
-
Umehara Ken
Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pha
-
Shimokawa Yoshihiko
Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pha
-
Shimokawa Y
Tokushima Research Institute Otsuka Pharmaceutical Co. Ltd.
-
Miyamoto G
Tokushima Research Institute Otsuka Pharmaceutical Co. Ltd.
-
Miyamoto Gohachiro
Department Of Drug Metabolism Tokushima Research Institute Otsuka Pharmaceutical Co. Ltd.
-
Miyamoto Gohachirou
Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co.,Ltd.,
関連論文
- Studies on Constituents from Chamaecyparis pisifera and Antibacterial Activity of Diterpenes
- 2 ガガイモ科及びナス科植物のステロイドとその細胞分化誘導活性(口頭発表の部)
- Cell Differentiation-Inducing Diterpenes from Andrographis paniculata NEES
- Studies on Differentiation-Inducers from Arctium Fructus
- Studies on the Differentiation Inducers of Myeloid Leukemic Cells from Citrus Species
- Studies on Differentiation-Inducing Activities of Triterpenes
- Studies on the Saponins of Lonicera japonica THUNB.
- Inhibition of Xanthine Oxidase by Anthraquinones(Pharmacognosy,Chemical)
- Studies on Differentiation Inducers. V. Steroid Glycosides from Periplocae Radicis Cortex
- Studies on the Constituents of Polygala japonica HOUTT. II. Structures of Polygalasaponins XI-XIX
- Studies on the Constituents of Polygala japonica HOUTT. I. Structures of Polygalasaponins I-X
- Studies on Differentiation Inducers. IV. Pregnane Derivatives from Condurango Cortex
- Monoamine Oxidase Inhibitors from Cinchonae Cortex
- Studies on the Constituents of Leaves of Citrus unshiu MARCOV.
- Antitumor-Promoting Constituents from Chaenomeles sinensis KOEHNE and Their Activities in JB6 Mouse Epidermal Cells
- Carrier-Mediated Uptake of Grepafloxacin, a Fluoroquinolone Antibiotic, by the Isolated Rat Lung Cells
- Differentiation Inducing Activities of Isocoumarins from Hydrangea Dulcis Folium
- Studies on Differentiation Inducers. VI.Lignan Derivatives from Arctium Fructus. (2)
- Physiologically-based Pharmacokinetic Analysis of Grepafloxacin
- Kaurane-Type Diterpenes from Adenostemma lavenia O. KUNTZE
- Sesquiterpene Glycosides and Saponins from Cynara cardunculus L.
- Sesquiterpene Lactones from Cichorium endivia L. and C. intybus L. and Cytotoxic Activity
- Five New Triterpene Saponins, Polygalasaponins XXVIII-XXXII from the Root of Polygala japonica HOUTT.
- Studies on the Constituents of Polygala japonica HOUTT. III. Structures of Polygalasaponins XX-XXVII
- STUDIES ON DIFFERENTIATION INDUCERS FROM PLANTS
- PC84 Isolation of Differentiation Inducers from Plant Sources
- Nine New Triterpene Saponins, Polygalasaponins XXXIII-XLI from the Roots of Polygala fallax HEMSL.
- Phytoestrogens from Aspalathus linearis(Pharmacognosy)
- Umbelliferone Released from Hairy Root Cultures of Pharbitis nil Treated with Copper Sulfate and Its Subsequent Glucosylation
- Effect of γ-Oryzanol on Cytochrome P450 Activities in Human Liver Microsomes(Biopharmacy)
- Effect of Probucol on Cytochrome P450 Activities in Human Liver Microsomes
- Prolyl Endopeptidase Inhibitors from the Roots of Lindera strychnifolia F. VILL
- Inhibition of Human Drug Metabolizing Cytochrome P450 by Buprenorphine
- Constituents from the Roots of Taraxacum platycarpum and Their Effect on Proliferation of Human Skin Fibroblasts
- Constituents from the Roots of Taraxacum platycarpum and Their Effect on Proliferation of Human Skin Fibroblasts