Branch R A, Shand D G
Clin Pharmacokinet. 1979 Mar-Apr;4(2):104-10. doi: 10.2165/00003088-197904020-00003.
It has previously been suggested that subjects who are initially slow metabolisers of drugs have a greater potential for induction of their drug metabolising enzymes than subjects with initial high rates of metabolism. This inference is based on observations made of changes in half-life of antipyrine. The purpose of this presentation is to reanalyse data previously presented in the literature with reference to clearance, a more precise estimate of drug metabolising activity, and half-life a parameter derived from both clearance and distribution. In one study in non-obese subjects, approximately 80% of intersubject variation in the change of total antipyrine clearance can be explained by differences in body size, particularly differences in liver volume. Furthermore, the relationship between initial antipyrine half-life and the percentage change in antipyrine half-life following induction can be explained by the association between each parameter and body weight. These observations imply that the potential for enzyme induction, and therefore for drug interactions based on enzyme induction, is present in all subjects and that intersubject variance in steady-state drug concentrations are as wide following induction as before induction.
此前有人提出，最初为药物慢代谢者的受试者比最初代谢率高的受试者具有更大的诱导其药物代谢酶的潜力。这一推断基于对安替比林半衰期变化的观察。本报告的目的是参照清除率（对药物代谢活性更精确的估计）和半衰期（一个由清除率和分布推导得出的参数），重新分析文献中先前呈现的数据。在一项针对非肥胖受试者的研究中，安替比林总清除率变化中约80%的受试者间差异可由体型差异，尤其是肝脏体积差异来解释。此外，初始安替比林半衰期与诱导后安替比林半衰期的百分比变化之间的关系可由每个参数与体重之间的关联来解释。这些观察结果表明，所有受试者都存在酶诱导的潜力，因此基于酶诱导的药物相互作用的潜力也存在，并且诱导后稳态药物浓度的受试者间差异与诱导前一样大。
