Interindividual variations in levels and activities of cytochrome P-450 inliver microsomes of Chinese subjects

Citation
Y. Shu et al., Interindividual variations in levels and activities of cytochrome P-450 inliver microsomes of Chinese subjects, ACT PHAR SI, 22(3), 2001, pp. 283-288
Citations number
23
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ACTA PHARMACOLOGICA SINICA
ISSN journal
02539756 → ACNP
Volume
22
Issue
3
Year of publication
2001
Pages
283 - 288
Database
ISI
SICI code
0253-9756(200103)22:3<283:IVILAA>2.0.ZU;2-0
Abstract
AIM: To compare the level and/or activity of several important cytochrome P -450 (CYP) enzymes in liver microsomes prepared from different Chinese subj ects. METHODS: Individual CYP contents, including CYP1A2, CYP2C9, and CYP3A 4, in liver microsomes of 17 Han, 17 Zhuang, and 8 Miao subjects were deter mined by using Western blot analysis and densitometric scanning. The substr ates for measuring the activity of individual CYP in vitro included phenace tin, tolbutamide, debrisoquine, and omeprazole. RESULTS: There was a large interindividual variability in the content and activity of CYP1A2, 2C9 and 3A4. And the activity of CYP2D6 also varied greatly between individual samp les. CYP3A4 (32 %) is the most abundant CYP in Chinese liver microsomes, an d the levels of CYP2C9 (19 %) and CYP1A2 (16 %) were also considerable. No clear ethnic, sex- and age-related differences in individual CYP content an d catalytic activity were detected in 42 Chinese liver samples, except that there were somewhat ethnic and sex-related differences in the content and activity of CYP1A2. Good correlation between enzyme protein content and act ivity was found for CYP1A2, 2C9 and 3A4. CONCLUSION: Our results may provid e useful information for the study of drug metabolism by liver microsomes i n Chinese.