title: Pharmacokinetics of two common antiretroviral regimens in older HIV-infected patients: a pilot study.
abstract: OBJECTIVE
  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.
authors: UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569, USA. jdumond@unc.edu
authors: J B
authors: JB
authors: Dumond
authors: J L
authors: JL
authors: Adams
authors: H M A
authors: HM
authors: Prince
authors: R L
authors: RL
authors: Kendrick
authors: R
authors: R
authors: Wang
authors: S H
authors: SH
authors: Jennings
authors: S
authors: S
authors: Malone
authors: N
authors: N
authors: White
authors: C
authors: C
authors: Sykes
authors: A H
authors: AH
authors: Corbett
authors: K B
authors: KB
authors: Patterson
authors: A
authors: A
authors: Forrest
authors: A D M
authors: AD
authors: Kashuba
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001741:Black or African American / Q000208:ethnology; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003521:Cyclopropanes; D003627:Data Interpretation, Statistical; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D016330:Frail Elderly; D006678:HIV / Q000187:drug effects / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D044465:White People / Q000208:ethnology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir
keywords: aging; intracellular pharmacokinetics; pharmacokinetics