Efavirenz Plasma Concentrations and Cytochrome 2B6 Polymorphisms
Efavirenz Plasma Concentrations and Cytochrome 2B6 Polymorphisms
复制标题
DOI：
10.1345/aph.1p141
复制
发表时间：
2010-10-01
影响因子：
2.9
通讯作者：
Winslow, Dean L.
中科院分区：
文献类型：
--
作者：
Lindfelt, Tristan;O'Brien, John;Winslow, Dean L.
背景：依非韦伦浓度的患者间变异性可能是由于CYP 2B 6基因多态性。依法韦仑浓度和药物基因组学数据是稀缺的Latino patients.OBJECTIVE：要评估艾滋病毒阳性拉丁美洲和白色患者之间的依法韦仑血浆浓度谷和中点的差异。此外，本研究评估了拉丁美洲和白色HIV阳性subjects.METHODS：这项试点研究包括10个拉丁美洲人和10个白人之间的关联依法韦仑浓度和CYP 2B 6多态性。测定了两个依法韦仑血药浓度：谷浓度和中点浓度。分析CYP 2B 6基因516（G到T）和785（A到G）密码子的遗传多态性。Mann-Whitney检验用于确定依非韦伦浓度是否随种族而变化。Kruskal-Wallis检验用于确定依法韦仑浓度是否随CYP 2B 6遗传多态性而变化。依法韦仑浓度表示为中位数（最小值、最大值）。结果：白人和拉丁裔的中点浓度分别为1.58 μ g/mL（1.36，6.02）和3.14 μ g/mL（1.74，7.72）（p < 0.05）。谷浓度并不因种族而异。10%的拉丁美洲人和白人的CYP 2B 6 -516和CYP 2B 6 -785纯合变体检测呈阳性。1例白色受试者的CYP 2B 6 -1459纯合变体检测结果呈阳性。5167 516 GT和516 GG（野生型）的谷浓度分别为5.13 μ g/mL（4.13，6.12）、2.13 μ g/mL（1.33，3.37）和1.44 μ g/mL（0.59，2.92）（p < 0.05）。785 GG、785 AG和785 AA（野生型）的谷浓度分别为5.12 μ g/mL（4.13，6.12）、1.98 μ g/mL（1.33，3.37）和1.27 μ g/mL（0.59，2.92）（p < 0.05）。没有一个患者服用影响CYP 2B 6 metabolics.CONCLUSIONS：依法韦仑谷浓度显着较高的785（A至G）和516（G至T）变异的患者。拉丁美洲人的中点依法韦仑浓度显著高于白人。
BACKGROUND: Interpatient variability in efavirenz concentrations may be due to CYP2B6 genetic polymorphisms. Efavirenz concentration and pharmacogenomic data are scarce in Latino patients.OBJECTIVE: To evaluate the difference in trough and midpoint efavirenz plasma concentrations between HIV-positive Latino and white patients. In addition, this study evaluated the association between efavirenz concentrations and CYP2B6 polymorphisms in Latino and white HIV-positive subjects.METHODS: This pilot study included 10 Latinos and 10 whites. Two efavirenz blood concentrations were determined: a trough and a midpoint. CYP2B6 genetic polymorphisms were analyzed at the 516 (G to T) and 785 (A to G) codons. The Mann-Whitney test was used to determine whether efavirenz concentrations varied with ethnicity. The Kruskal-Wallis test was used to determine whether efavirenz concentrations varied with CYP2B6 genetic polymorphisms. Efavirenz concentrations were expressed as medians (minimum, maximum).RESULTS: Midpoint concentrations were 1.58 mu g/mL (1.36, 6.02) and 3.14 mu g/mL (1.74, 7.72) for whites and Latinos, respectively (p < 0.05). Trough concentrations did not vary as a function of ethnicity. Ten percent of Latinos and whites tested positive for homozygous variants of CYP2B6-516 and CYP2B6-785. One white subject tested positive for the homozygous variant of CYP2B6-1459. Trough concentrations for 5167 516GT, and 516GG (wild type) were 5.13 mu g/mL (4.13, 6.12), 2.13 mu g/mL (1.33, 3.37), and 1.44 mu g/mL (0.59, 2.92), respectively (p < 0.05). Trough concentrations for 785GG, 785AG, and 785AA (wild type) were 5.12 mu g/mL (4.13, 6.12), 1.98 mu g/mL (1.33, 3.37), and 1.27 mu g/mL (0.59, 2.92), respectively (p < 0.05). None of the patients took concomitant medications that impacted CYP2B6 metabolism.CONCLUSIONS: Trough efavirenz concentrations were significantly higher in patients with the 785 (A to G) and 516 (G to T) variants. Midpoint efavirenz concentrations in Latinos were significantly higher than those of whites.