CYP3A5基因型对肾移植患者从头至尾LCP他克莫司给药和监测的影响。

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Nikhil Rao, Taylor Carcella, Neha Patel, Felicia Bartlett, Maria Aurora Posadas, Michael Casey, Derek A Dubay, David J Taber
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引用次数: 0

摘要

目的:LCP tac在肾移植中的推荐起始剂量为0.14 mg/kg/天。本研究的目的是评估CYP3A5对围手术期LCP tac给药和监测的影响。方法:这是一项前瞻性观察队列研究,研究对象是成年肾受体接受重新LCP治疗。测定CYP3A5基因型,评价90天药代动力学和临床疗效。将患者分为CYP3A5表达型(*1纯合或杂合)和非表达型(LOF *3/*6/*7等位基因)。结果:本次研究共筛选120人,联系90人,同意52人;50例有基因型结果,22例表达CYP3A5*1。非裔美国人(AA)占非表达者的37.5%,占表达者的81.8% (P = 0.001)。CYP3A5组间LCP tac初始剂量相似(0.145 vs 0.137 mg/kg/day;P = 0.161),而表达物的稳态剂量更高(0.150 vs. 0.117 mg/kg/day;P = 0.026)。CYP3A5*1表达者在低于6 ng/ml的tac谷浓度显著增加,在高于14 ng/ml的tac谷浓度显著减少。CYP3A5表达者与非表达者相比,提供者更有可能将LCP tac下调10%和20% (P < 0.03)。在序列建模中,CYP3A5基因型状态比AA种族更能解释LCP tac的剂量要求。结论:CYP3A5*1表达者需要更高剂量的LCP tac才能达到治疗浓度,并且亚治疗谷浓度的风险更高,持续30天。CYP3A5表达者的LCP剂量变化更可能被提供者低估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of CYP3A5 genotype on de-novo LCP tacrolimus dosing and monitoring in kidney transplantation.

Objectives: LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring.

Methods: This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele).

Results: In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race.

Conclusion: CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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