| Autor: |
Dumond, JB, Adams, JL, Prince, HMA, Kendrick, RL, Wang, R, Jennings, SH, Malone, S, White, N, Sykes, C, Corbett, AH, Patterson, KB, Forrest, A, Kashuba, ADM |
| Předmět: |
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| Zdroj: |
HIV Medicine; Aug2013, Vol. 14 Issue 7, p401-409, 9p |
| Abstrakt: |
Objectives 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. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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