title: Within-patient atazanavir trough concentration monitoring in HIV-1-infected patients.
abstract: OBJECTIVE
  Protease inhibitors (PIs) exhibit considerable interpatient pharmacokinetic variability in plasma trough concentrations. Therapeutic drug monitoring (TDM) is occasionally used to guide chronic dosing to achieve target trough concentrations, but its clinical success assumes minimal intrasubject variability. Therefore, our primary objective was to evaluate intrapatient variability in atazanavir (ATV) plasma trough concentrations in HIV-1-infected patients.
  
  
  METHODS
  In a single-site, prospective, cohort study, patients on atazanavir with or without ritonavir (ATV/r or ATV) for 2 clinic visits were enrolled. Adherence and time since last dose (TSLD) were verified at each visit. ATV was assayed with high-performance liquid chromatography. Intra- and interpatient variation was evaluated using the median intraindividual percentage coefficient of variation (ICV).
  
  
  RESULTS
  The mean 24-hour ATV trough concentrations for the first and second visit for the ATV/r group (n = 10) was 598 (CV 84%) and 525 ng/mL (CV 66%), respectively (P = .511), and 300 (CV 81%) and 434 ng/mL (CV 106%) for the ATV group (n = 4), respectively (P = .369). Median ICV was 43.1% for all patients (range: 0.6%-107.6%), 38.1% (0.6%-107.6%) for the ATV/r group, and 33.1% (2.3%-87.6%) for the ATV group.
  
  
  CONCLUSIONS
  Potential intrapatient variability in ATV troughs suggests that repeated measurements may be required to ensure that target values are maintained.
authors.affiliation: Department of Clinical Sciences and Administration, University of Houston, College of Pharmacy, Houston, TX 77030, USA. rdcrutchley@uh.edu
authors.forename: Rustin D
authors.initials: RD
authors.lastname: Crutchley
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Adel
authors.initials: A
authors.lastname: Sulaiman
authors.forename: Jill
authors.initials: J
authors.lastname: Hochreitter
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069446:Atazanavir Sulfate; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009842:Oligopeptides / Q000008:administration & dosage*; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir