Lennard M S
University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, U.K.
Pharmacol Toxicol. 1990 Oct;67(4):273-83. doi: 10.1111/j.1600-0773.1990.tb00830.x.
Polymorphic oxidation of the sparteine/debrisoquine-type has been shown to account for much of the interindividual variation in the metabolism, pharmacokinetics and pharmacodynamics of an increasing number of drugs, including some antiarrhythmic, antidepressant and beta-adrenoceptor antagonist agents. Impaired hydroxylation of these drugs results from the absence of the enzyme cytochrome P450IID6 in the livers of poor metabolisers, who constitute 6% to 10% of Caucasian populations. The clinical importance of the phenomenon has to be explored further and for most sparteine/debrisoquine-related substrates there is a need for controlled prospective studies to define the consequences to the patient of impaired or enhanced drug oxidation.
已证明,司巴丁/异喹胍型多态性氧化是越来越多药物代谢、药代动力学和药效学个体间差异的主要原因,这些药物包括一些抗心律失常药、抗抑郁药和β-肾上腺素受体拮抗剂。在代谢缓慢者的肝脏中,由于缺乏细胞色素P450IID6酶,这些药物的羟基化作用受损,代谢缓慢者占白种人群的6%至10%。这一现象的临床重要性有待进一步探究,对于大多数与司巴丁/异喹胍相关的底物,需要进行对照前瞻性研究,以确定药物氧化受损或增强对患者的影响。