Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Pharmacogenomics. 2019 Mar;20(4):225-240. doi: 10.2217/pgs-2018-0166. Epub 2019 Feb 15.
We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin.
MATERIALS & METHODS: Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics.
Among 172 patients, 18, 43 and 34% were classified as rapid, intermediate and slow NAT2 acetylators, respectively. Of the 58 patients contributing drug concentrations, rapid and intermediate acetylators had 2.3- and 1.6-times faster isoniazid clearance than slow acetylators. No association was observed between rifampicin pharmacokinetics and SLCO1B1, ABCB1, UGT1A or PXR genotypes.
Clinical relevance of the effects of genetic variation on isoniazid concentrations and low first-line tuberculosis drug exposures observed require further investigation.
我们报告异烟肼和利福平的药代动力学参数的遗传变异性的流行率和影响。
使用 TaqMan 基因分型开放式阵列，确定 SLCO1B1、NAT2、PXR、ABCB1 和 UGT1A 基因的基因型。采用非线性混合效应模型描述药物的药代动力学。
在 172 名患者中，分别有 18%、43%和 34%被归类为快速、中间和缓慢 NAT2 乙酰化酶。在 58 名提供药物浓度的患者中，快速和中间乙酰化酶的异烟肼清除率比缓慢乙酰化酶快 2.3 倍和 1.6 倍。未观察到 SLCO1B1、ABCB1、UGT1A 或 PXR 基因型与利福平药代动力学之间存在相关性。
需要进一步研究遗传变异对异烟肼浓度和一线抗结核药物低暴露的影响的临床相关性。
