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

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.