目的:以苯丙胺为基础的药物被推荐作为治疗儿童和青少年注意力缺陷/多动障碍的一线药物治疗。然而,这些药物的疗效和耐受性因个体而异,这可能与苯丙胺代谢的个体差异有关。这项研究检查了在接受苯丙胺治疗的年轻人中,细胞色素P450同工酶CYP2D6的基因型预测表型是否与自我报告的副作用和症状改善有关。
方法:从加拿大西部招募了2,14名年龄在6-24岁的有过去或现在的苯丙胺治疗史的参与者。收集参与者的苯丙胺剂量和持续时间信息以及有关依从性的问题,合并用药,症状改善和副作用。从唾液样品中提取DNA并对CYP2D6进行基因分型。二项逻辑回归模型用于确定CYP2D6代谢表型的影响,有和没有校正表型转换对自我报告的症状改善和副作用。
结果:基因型预测的CYP2D6代谢不良者在校正表型转换和调整性别后,与中间代谢者相比,报告症状改善的几率明显更高(OR=3.67,95%CI=1.15-11.7,P=0.029)。年龄,剂量,持续时间,和坚持。CYP2D6代谢表型与自我报告的副作用之间没有关联。
结论:我们的研究结果表明,在接受苯丙胺治疗的儿童和青少年中,表型转化和基因型预测的CYP2D6代谢不良表型与症状改善的几率显著相关。如果复制,这些结果可以为儿童和青少年苯丙胺治疗的未来剂量指南的制定提供信息.
OBJECTIVE: Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with
amphetamines.
METHODS: Two hundred fourteen participants aged 6-24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6 . Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects.
RESULTS: Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15-11.7, P = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects.
CONCLUSIONS: Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.