Kotlyar M, Carson S W
School of Pharmacy, The University of North Carolina, Chapel Hill 27599-7360, USA.
Int J Clin Pharmacol Ther. 1999 Jan;37(1):8-19.
This review evaluates the effect of obesity on the various isozymes of the cytochrome P450 enzyme system.
A Medline search of the international literature on drug metabolism and obesity from 1966 to early 1998 was conducted. All English language studies in humans that compared the pharmacokinetics of a given medication between obese and non-obese subjects were evaluated. Any study in which the substrate examined is excreted unchanged, not metabolized primarily by a single cytochrome P450 isozyme or which is considered a high extraction compound was excluded from this review.
Despite the prevalence of obesity, the known health consequences of obesity and the increase of medication usage in the obese population, very few studies have attempted to establish the effect of this condition on the cytochrome P450 enzyme system. Numerous studies, however, have compared pharmacokinetic parameters between obese and non-obese subjects for individual drugs. By examining those trials in which the agents studied all undergo biotransformation via the same CYP450 isozyme, a preliminary appreciation of the effect of obesity on the activity of that particular isozyme can be attained.
The effect of obesity on CYP450 appears to be isozyme-specific with the activity of cytochrome P450 3A4 decreasing and that of cytochrome P450 2E1 increasing. The effect of obesity on the cytochrome P450 1A2, 2C9, 2C19, and 2D6 isozymes is inconclusive.
本综述评估肥胖对细胞色素P450酶系统各同工酶的影响。
对1966年至1998年初关于药物代谢和肥胖的国际文献进行了Medline检索。评估了所有在人类中进行的、比较肥胖和非肥胖受试者之间给定药物药代动力学的英文研究。任何研究中所检测的底物以原形排泄、不是主要由单一细胞色素P450同工酶代谢或被认为是高摄取化合物的研究均被排除在本综述之外。
尽管肥胖普遍存在，肥胖已知的健康后果以及肥胖人群中药物使用的增加，但很少有研究试图确定这种情况对细胞色素P450酶系统的影响。然而，许多研究比较了肥胖和非肥胖受试者之间个别药物的药代动力学参数。通过检查那些所研究的药物均通过相同的CYP450同工酶进行生物转化的试验，可以初步了解肥胖对该特定同工酶活性的影响。
肥胖对CYP450的影响似乎具有同工酶特异性，细胞色素P450 3A4的活性降低，而细胞色素P450 2E1的活性增加。肥胖对细胞色素P450 1A2、2C9、2C19和2D6同工酶的影响尚无定论。
