title: Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens.
abstract: OBJECTIVE
  The purpose of this study was to determine the pharmacokinetics and tolerability of three different indinavir and lopinavir/ritonavir dosing regimens.
  
  
  METHODS
  HIV-infected adults receiving lopinavir/ritonavir 400/100 mg twice daily with food had nine plasma samples taken over a 12 h dosing interval at baseline (BL), after adding indinavir 600 mg twice daily for 10 days (R1), indinavir 800 mg twice daily for 5 days (R2) and lopinavir/ritonavir 533/133 mg plus indinavir 600 mg twice daily for 10 days (R3). Plasma samples were assayed using HPLC.
  
  
  RESULTS
  A total of 12 patients completed the BL visit [10 male; mean (SD) age=43.9 (5.8) years] and 9, 7 and 7 completed R1, R2 and R3 visits, respectively. Two subjects discontinued treatment due to hypertriglyceridaemia. Compared with BL, the R3 lopinavir AUC (P<0.05) and Cmin (P=0.0025) were significantly higher and the R2 AUC trended higher (P=0.09). The indinavir AUC (P=0.030) and Cmax (P=0.035) were significantly higher for R2 compared with R1. There was a trend for increased total bilirubin (TB) after the addition of indinavir (P=0.09). Lopinavir and indinavir AUC, Cmax and Cmin were associated with TB during univariate analyses (P<0.01) while only lopinavir AUC (P=0.0004) and indinavir AUC (P=0.0028) were associated with TB during multivariate analysis. Only indinavir AUC was significant when both drugs were included in the model (P=0.0028).
  
  
  CONCLUSIONS
  Elevated lopinavir and indinavir concentrations are associated with elevated TB.
authors.affiliation: Department of Pharmacy and Pharmaceutical Science, University at Buffalo, Buffalo, NY, USA. robert_dicenzo@urmc.rochester.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Dicenzo
authors.forename: Amneris
authors.initials: A
authors.lastname: Luque
authors.forename: Panupoong
authors.initials: P
authors.lastname: Larppanichpoonphol
authors.forename: Richard
authors.initials: R
authors.lastname: Reichman
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019469:Indinavir; D001663:Bilirubin