Klomp Sylvia D, Manson Martijn L, Guchelaar Henk-Jan, Swen Jesse J
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Leiden Network for Personalised Therapeutics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
J Clin Med. 2020 Sep 7;9(9):2890. doi: 10.3390/jcm9092890.
Phenoconversion is the mismatch between the individual's genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic review was conducted to investigate factors contributing to phenoconversion and the impact on cytochrome P450 metabolism. Twenty-seven studies met the inclusion criteria and were incorporated in this review, of which 14 demonstrate phenoconversion for a specific genotype group. Phenoconversion into a lower metabolizer phenotype was reported for concomitant use of CYP450-inhibiting drugs, increasing age, cancer, and inflammation. Phenoconversion into a higher metabolizer phenotype was reported for concomitant use of CYP450 inducers and smoking. Moreover, alcohol, pregnancy, and vitamin D exposure are factors where study data suggested phenoconversion. The studies reported genotype-phenotype discrepancies, but the impact of phenoconversion on the effectiveness and toxicity in the clinical setting remains unclear. In conclusion, phenoconversion is caused by both extrinsic factors and patient- and disease-related factors. The mechanism(s) behind and the extent to which CYP450 metabolism is affected remain unexplored. If studied more comprehensively, accounting for phenoconversion may help to improve our ability to predict the individual CYP450 metabolism and personalize drug treatment.
表型转换是指由于非遗传因素导致个体基于基因型对药物代谢的预测与实际药物代谢能力不匹配的情况。虽然表型转换的概念已在叙述性综述中有所描述，但尚无系统性综述。本研究进行了一项系统性综述，以调查导致表型转换的因素及其对细胞色素P450代谢的影响。27项研究符合纳入标准并纳入本综述，其中14项研究证明了特定基因型组存在表型转换。据报道，同时使用CYP450抑制药物、年龄增长、癌症和炎症会导致表型转换为代谢能力较低的表型。据报道，同时使用CYP450诱导剂和吸烟会导致表型转换为代谢能力较高的表型。此外，酒精、妊娠和维生素D暴露也是研究数据表明会导致表型转换的因素。这些研究报告了基因型-表型差异，但表型转换在临床环境中对有效性和毒性的影响仍不明确。总之，表型转换是由外在因素以及患者和疾病相关因素共同引起的。细胞色素P450代谢受影响的背后机制和程度仍有待探索。如果进行更全面的研究，考虑表型转换可能有助于提高我们预测个体细胞色素P450代谢和实现药物治疗个体化的能力。
