Application of the PKCYP-test in Cases of Altered CYP1A2 for Multiple CYP Systems in Rat Models of Disease
スポンサーリンク
概要
- 論文の詳細を見る
Previously, we established a method to assess drug metabolism capacity based on a pharmacokinetic estimation of the quantity of cytochrome P450(CYP)in vivo(PKCYP-test)by introducing an apparent liver-to-blood free concentration gradient in vivo(qg). The qg values were determined as the ratio of in vivo-in vitro clearance. In this study, we examined the application of the PKCYP-test to the clearance of acetanilide and caffeine mediated by CYP1A2 using rat models in which the levels of CYP enzymes were reduced. Rats fed a choline-deficient diet(CD-fed)and aged rats were used as models for a low level of CYP in the liver. In both rat models, the contribution(f_<CYP>)of CYP1A2 to the in vivo intrinsic clearance values(CL_<int>)of acetanilide and caffeine metabolism was less than unity, suggesting that other metabolic pathways are involved in the CL_<int>. The in vivo clearance for CYP1A2 was estimated by multiplying f_<CYP> by CL_<int> then the value of qg was determined as the ratio of in vivo-in vitro clearance. We predicted the level of CYP1A2 in CD-fed and aged rats, based on the clearance of acetanilide mediated by CYP1A2, using the qg value of control rats. The clearance of caffeine mediated by CYP1A2 in CD-fed and aged rats, as estimated from the predicted level of CYP1A2, correlated with the observed values. In conclusion, we have demonstrated that the PKCYP-test can be applied to CYP1A2 for drugs metabolized by multiple CYP isozymes, and/or to models involving reduced CYP.
- 公益社団法人日本薬学会の論文
- 2001-09-01
著者
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Kose Matsunaga
Department Of Practical Pharmacy Kyoritsu College Of Pharmacy
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Nakashima E
Dep. Of Pharmaceutics Kyoritsu Univ. Of Pharmacy
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Nakashima Emi
Faculty Of Pharmaceutical Sciences Kanazawa University
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Nakashima Emi
Department Of Pharmaceutics Kyoritsu University Of Pharmacy
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Nakashima Emi
Department Of Pediatrics:hospital Pharmacy:and Faculty Of Pharmaceutical Sciences University Of Kana
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Iizasa H
Kyoritsu Univ. Pharmacy Tokyo Jpn
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Iizasa Hisashi
Department Of Pharmaceutics Kyoritsu University Of Pharmacy
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HATTORI Kenji
Department of Otolaryngology, Sumitomo Hospital
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Takahashi Atsushi
Division Of Pharmacology National Institute Of Hygienic Sciences
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KIZU Junko
Practical Pharmacy, Kyoritu College of Pharmacy
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Kizu J
Department Of Practical Pharmacy Kyoritsu University Of Pharmacy
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Kizu J
Kyoritsu Univ. Pharmacy Tokyo Jpn
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Kizu Junko
Practical Pharmacy Kyoritu College Of Pharmacy
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中島 恵美
共立薬科大学 薬剤学講座
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Nakashima Emi
Faculty Of Pharmaceutical Sciences And Hospital Pharmacy Kanazawa University
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Hattori Kenji
Department Of Pharmaceutics Kyoritsu College Of Pharmacy
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Matsunaga Noriko
Department Of Practical Pharmacy Kyoritsu College Of Pharmacy
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TAKANAKA Akira
The Organization for Pharmaceutical Safety and Research
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Takanaka Akira
Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
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Takanaka A
National Inst. Hygienic Sciences Tokyo Jpn
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中島 恵美
Department Of Pharmaceutics Kyoritsu University Of Pharmacy
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Takahashi A
Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
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Hattori Kenji
Department Of Otolaryngology Sumitomo Hospital
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HATTORI Kenji
Department of Material Physics, Faculty of Engineering Science, Osaka University
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