Waring R H, Emery P
School of Biochemistry, University of Birmingham, UK.
Br Med Bull. 1995 Apr;51(2):449-61. doi: 10.1093/oxfordjournals.bmb.a072972.
Individual variation in drug metabolism has been extensively investigated. Population studies have shown that there is a wide range in metabolising ability for all detoxification pathways; the distributions may be unimodal (Gaussian) or polymodal, with subsets of individuals who differ from the majority. These may be poor metabolisers (PM) or extensive metabolisers (EM). In many cases, these phenotypes can be linked with the genotype. Frequently the PM phenotype is more susceptible to drug toxicity, while the EM phenotype requires increased dosage for therapeutic benefit. In some cases, phenotypes or genotypes appear to have increased susceptibility to clinical disease. These ideas are discussed for the cytochrome P-450 isozymes, FMO system, cysteine dioxygenase-linked oxidations, glucuronidation, sulphation, acetylation, glutathione conjugation and methylation pathways.
药物代谢的个体差异已得到广泛研究。群体研究表明，所有解毒途径的代谢能力存在很大差异；其分布可能是单峰的（高斯分布）或多峰的，存在与大多数个体不同的亚组。这些个体可能是代谢缓慢者（PM）或快代谢者（EM）。在许多情况下，这些表型可与基因型相关联。通常，PM表型更容易受到药物毒性影响，而EM表型则需要增加剂量才能获得治疗效果。在某些情况下，表型或基因型似乎对临床疾病的易感性增加。本文将针对细胞色素P - 450同工酶、黄素单加氧酶系统、半胱氨酸双加氧酶相关氧化、葡萄糖醛酸化、硫酸化、乙酰化、谷胱甘肽结合和甲基化途径对这些观点进行讨论。
