JAC Advance Access originally published online on June 7, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):393-400; doi:10.1093/jac/dkl238
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Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens
1 Department of Pharmacy and Pharmaceutical Science, University at Buffalo Buffalo, NY, USA 2 Infectious Disease Unit, Department of Medicine, University of Rochester Rochester, NY, USA
Received 6 January 2006; returned 28 February 2006; revised 23 March 2006; accepted 12 May 2006
*Correspondence address. Infectious Disease Unit, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. Tel: +1-585-275-6249; Fax: +1-585-275-7896; E-mail: robert_dicenzo{at}urmc.rochester.edu
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.
Keywords: drug monitoring , HIV antiviral pharmacology , pharmacokinetics
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