Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens

Robert Dicenzo, Amneris Luque, Panupoong Larppanichpoonphol, Richard Reichman

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)393-400
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number2
DOIs
StatePublished - Aug 2006

Keywords

  • Drug monitoring
  • HIV antiviral pharmacology
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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