التفاصيل البيبلوغرافية
| العنوان: |
The influence of temperature on the metabolic activity of CYP2C9, CYP2C19, and CYP3A4 genetic variants in vitro. |
| المؤلفون: |
Kojima, Michiaki, Machida, Kanami, Cho, Sumie, Watanabe, Daichi, Seki, Hiroyuki, Shimoji, Miyuki, Imaoka, Ayuko, Yamazaki, Hiroshi, Guengerich, F. Peter, Nakamura, Katsunori, Yamamoto, Koujirou, Akiyoshi, Takeshi, Ohtani, Hisakazu |
| المصدر: |
Xenobiotica; May2023, Vol. 53 Issue 5, p357-365, 9p |
| مصطلحات موضوعية: |
CYTOCHROME P-450 CYP2C19, GENETIC variation, CYTOCHROME P-450 CYP3A, TEMPERATURE, GENETIC polymorphisms, CYTOCHROME P-450, OMEPRAZOLE |
| مستخلص: |
1. Temperature is considered to affect the activity of drug-metabolizing enzymes; however, no previous studies have compared temperature dependency among cytochrome P450 genetic variants. This study aimed to analyse warfarin 7-hydroxylation by CYP2C9 variants; omeprazole 5-hydroxylation by CYP2C19 variants; and midazolam 1-hydroxylation by CYP3A4 variants at 34 °C, 37 °C, and 40 °C. 2. Compared with that seen at 37 °C, the intrinsic clearance rates (Vmax/Km) of CYP2C9.1 and.2 were decreased (76 ∼ 82%), while that of CYP2C9.3 was unchanged at 34 °C. At 40 °C, CYP2C9.1,.2, and.3 exhibited increased (121%), unchanged and decreased (87%) intrinsic clearance rates, respectively. At 34 °C, the clearance rates of CYP2C19.1A and.10 were decreased (71 ∼ 86%), that of CYP2C19.1B was unchanged, and those of CYP2C19.8 and.23 were increased (130 ∼ 134%). At 40 °C, the clearance rates of CYP2C19.1A,.1B,.10, and.23 remained unaffected, while that of CYP2C19.8 was decreased (74%). At 34 °C, the clearance rates of CYP3A4.1 and.16 were decreased (79 ∼ 84%), those of CYP3A4.2 and.7 were unchanged, and that of CYP3A4.18 was slightly increased (112%). At 40 °C, the clearance rate of CYP3A4.1 remained unaffected, while those of CYP3A4.2,.7,.16, and.18 were decreased (58 ∼ 82%). 3. These findings may be clinically useful for dose optimisation in patients with hypothermia or hyperthermia. [ABSTRACT FROM AUTHOR] |
|
Copyright of Xenobiotica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
PDF full text from Publisher