title: Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations.
abstract: BACKGROUND
  Atazanavir (ATV) is recommended to be dosed at 400 mg once daily or 300 mg daily coadministered with 100 mg ritonavir (RTV).
  
  
  METHODS
  31 male patients receiving ATV either alone or boosted with RTV for more than 2 weeks had ATV concentration measured by high performance liquid chromatography (HPLC). ATV concentrations were adjusted to obtain a 24-hour trough level using a standard pharmacokinetic formula.
  
  
  RESULTS
  25 samples were taken from patients who received 300 mg ATV, 6 with 200 mg, 3 with 400 mg, and 2 with 150 mg, all boosted with 100 mg RTV. In the unboosted group, patients received 400 mg (7) or 600 mg (2). The median adjusted 24-hour trough ATV concentration was 630 ng/mL (interquartile range [IQR] 355-1034) in the boosted and 113 ng/mL (IQR 50-225) in the unboosted group (p = .001). Median serum bilirubin concentration was 34 IU/L (IQR 27.5-49) and 41 IU/L (IQR 31-45) in the boosted and unboosted groups, respectively. In the boosted group, high ATV concentrations were significantly correlated with increased serum bilirubin concentrations (p = .003).
  
  
  CONCLUSIONS
  ATV concentrations showed considerable interpatient variability. Bilirubin concentrations are an indicator of high ATV concentrations and may prove to be useful in selecting patients for therapeutic drug monitoring (TDM).
authors.affiliation: Albion Street Centre, Sydney, NSW, Australia. don.smith@sesiahs.health.nsw.gov.au
authors.forename: Don E
authors.initials: DE
authors.lastname: Smith
authors.forename: Sarangapany
authors.initials: S
authors.lastname: Jeganathan
authors.forename: John
authors.initials: J
authors.lastname: Ray
mesh_terms: D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood*; D004359:Drug Therapy, Combination; D006678:HIV / Q000254:growth & development*; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood* / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D001663:Bilirubin