Gram L F
Département de Pharmacologie Clinique, Odense Université, Danemark.
Encephale. 1991 May-Jun;17 Spec No 1:123-5.
Genetic polymorphism related to certain P450 isozymes, in particular the sparteine/debrisoquine oxygenase, is the dominant cause of interindividual variation in elimination of several drugs. If the pharmacokinetic variability is large, relative to the therapeutic index of the drug, the genetic polymorphism will be clinically important. If the dose cannot be adjusted on the basis of effect measurements, phenotyping may be a supplement or replacement for drug level monitoring which is otherwise relevant for such drugs. Several aspects as elucidated by the experience with the sparteine/debrisoquine oxidation polymorphism ought to be analysed: The role of active metabolites and their rate of formation and elimination, selective drug-drug interaction at the polymorphic isozyme or at alternative routes of elimination, the possible role of two or more polymorphic drug oxidation pathways, and the effect of saturable kinetics. The sparteine/debrisoquine oxidation polymorphism affects two major classes of drugs in psychopharmacology, the antidepressants and the neuroleptics, and this is the best example of clinical relevance of pharmacogenetic polymorphism. Routine use of phenotyping thus should be considered for psychiatry departments.
与某些细胞色素P450同工酶相关的基因多态性，尤其是司巴丁/异喹胍氧化酶，是几种药物消除个体差异的主要原因。如果药代动力学变异性相对于药物的治疗指数较大，那么这种基因多态性在临床上就很重要。如果不能根据效应测量来调整剂量，那么表型分析可能是药物浓度监测的补充或替代方法，而药物浓度监测对于此类药物来说原本是相关的。应该分析司巴丁/异喹胍氧化多态性的经验所阐明的几个方面：活性代谢物的作用及其形成和消除速率、在多态性同工酶或替代消除途径上的选择性药物相互作用、两种或更多种多态性药物氧化途径的可能作用以及饱和动力学的影响。司巴丁/异喹胍氧化多态性影响精神药理学中的两大类药物，即抗抑郁药和抗精神病药，这是药物遗传学多态性临床相关性的最佳例子。因此，精神科应考虑常规使用表型分析。
