UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569, USA.
HIV Med. 2013 Aug;14(7):401-9. doi: 10.1111/hiv.12017. Epub 2013 Feb 24.
The pharmacokinetics (PK) of antiretrovirals (ARVs) in older HIV-infected patients are poorly described. Here, the steady-state PK of two common ARV regimens [tenofovir (TFV)/emtricitabine (FTC)/efavirenz (EFV) and TFV/FTC/atazanavir (ATV)/ritonavir (RTV)] in older nonfrail HIV-infected patients are presented.
HIV-infected subjects ≥ 55 years old not demonstrating the frailty phenotype were enrolled in an unblinded, intensive-sampling PK study. Blood plasma (for TFV, FTC, EFV, ATV and RTV concentrations) and peripheral blood mononuclear cells [PBMCs; for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations] were collected at 11 time-points over a 24-hour dosing interval. Drug concentrations were analysed using validated liquid chromatography-ultraviolet detection (LC-UV) or liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Noncompartmental pharmacokinetic analysis was used to estimate PK parameters [area under the concentration-time curve over 24 h (AUC0-24h ) and maximal concentration (Cmax )]. These parameters were compared with historical values from the general HIV-infected population.
Six subjects on each regimen completed the study. Compared with the general population, these elderly subjects had 8-13% decreased TFV AUC0-24h and Cmax , and 19-78% increased FTC and RTV AUC0-24h and Cmax . Decreased ATV AUC0-24h (12%) and increased Cmax (9%) were noted, while EFV exposure was unchanged (5%) with a 16% decrease in Cmax . Intracellular nucleoside/tide metabolite concentrations and AUC are also reported for these subjects.
This study demonstrates that the PK of these ARVs are altered by 5-78% in an older HIV-infected population. Implications of PK differences for clinical outcomes, particularly with the active nucleoside metabolites, remain to be explored. This study forms the basis for further study of ARV PK, efficacy, and toxicity in older HIV-infected patients.
抗逆转录病毒药物（ARV）在老年 HIV 感染者中的药代动力学（PK）描述较差。本研究介绍了两种常见 ARV 方案[替诺福韦（TFV）/恩曲他滨（FTC）/依非韦伦（EFV）和 TFV/FTC/阿扎那韦（ATV）/利托那韦（RTV）]在老年非虚弱 HIV 感染者中的稳态 PK。
未表现出虚弱表型的≥55 岁 HIV 感染者入组一项非盲、强化采样 PK 研究。采集血血浆（用于 TFV、FTC、EFV、ATV 和 RTV 浓度）和外周血单核细胞[PBMCs；用于替诺福韦二磷酸（TFV-DP）和恩曲他滨三磷酸（FTC-TP）浓度]，在 24 小时给药间隔内采集 11 个时间点的样本。使用经验证的液相色谱-紫外检测（LC-UV）或液相色谱串联质谱（LC-MS/MS）方法分析药物浓度。采用非房室药代动力学分析估算 PK 参数[24 小时内浓度-时间曲线下面积（AUC0-24h）和最大浓度（Cmax）]。将这些参数与一般 HIV 感染者的历史值进行比较。
每个方案均有 6 名受试者完成了研究。与一般人群相比，这些老年受试者的 TFV AUC0-24h 和 Cmax 降低 8-13%，FTC 和 RTV AUC0-24h 和 Cmax 升高 19-78%。ATV AUC0-24h 降低 12%（Cmax 升高 9%），EFV 暴露无变化（Cmax 降低 5%）。还报告了这些受试者的细胞内核苷/核苷酸代谢物浓度和 AUC。
本研究表明，在老年 HIV 感染者中，这些 ARV 的 PK 改变了 8-78%。PK 差异对临床结局的影响，特别是对活性核苷代谢物的影响，仍有待探讨。本研究为进一步研究老年 HIV 感染者的 ARV PK、疗效和毒性奠定了基础。
