遗传药理学对等离子体的影响lumefantrine孕妇药物动力学和疟疾治疗的结果。

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Mutagonda射频,Kamuhabwa AAR, Minzi OMS Massawe SN, Asghar M, Homann MV, Farnert, Aklillu E

遗传药理学对等离子体的影响lumefantrine孕妇药物动力学和疟疾治疗的结果。

颧骨j . 2017年7月3;16 (1):267。doi: 10.1186 / s12936 - 017 - 1914 - 9。

PubMed ID

28673292 (在PubMed

]

文摘

背景:怀孕的药代动力学特性有相当大的影响药物用于治疗无并发症恶性疟原虫疟疾。遗传变异的作用在抗疟疾药物处置和有效性在怀孕期间不调查。这项研究旨在考察药物基因学的影响在lumefantrine(低频)药物动力学和孕妇的治疗结果。方法:孕妇与无并发症恶性疟疾登记和治疗蒿甲醚和苯芴醇(ALu)在Mkuranga Kisarawe区医院坦桑尼亚海岸地区。第七天低频等离子体浓度和forCYP2B6 pcr (c。516 g > T, c.983T > C), CYP3A4 * 1 b, CYP3A5 * 3 * 6 *(7)种代号为ABCB1的和C。4036 a4g被确定。寄生虫量化的血涂片显微镜,干血对寄生虫使用qPCR筛查和基因分型和嵌套PCR在入学时收集28天来区分再感染复发。治疗的反应被记录后,协议。结果:共有92名孕妇在第二和第三阶段包括在这项研究中,424个样本筛查恶性疟原虫的存在。寄生虫在跟踪期间被发现在11(12%)治疗后7天到28天之间的女性和PCR基因分型结果证实了复发的女性感染7例(63.3%)。 The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4-17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in pregnant women followed up for 28 days (P = 0.018). CONCLUSIONS: Genetic variations in CYP3A4 and CYP3A5may influence LF pharmacokinetics and treatment outcome in pregnant women.

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药物酶

药物	酶	类	生物	药理作用	行动
蒿甲醚	细胞色素P450 3 a5	蛋白质	人类	未知的	底物	细节