Pharmacokinetic interaction between indinavir and darunavir with low-dose ritonavir in healthy volunteers.

Objective: To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista), indinavir (IDV, Crixivan) and low-dose ritonavir (RTV, Norvir).

Methods: In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.d.), treatment B (IDV/r 800/100 mg b.i.d.) and treatment C (DRV/r 400/100 mg b.i.d. + IDV 800 mg b.i.d.). On day 7, full pharmacokinetic profiles of DRV, IDV and RTV were determined. Safety and tolerability were also assessed.

Results: Based on the least-squares means ratios, the steady-state exposure (area under the curve, AUC(12h)) and plasma concentrations (C(min) and C(max)) of IDV were increased by 23, 125 and 8%, respectively, when DRV was co-administered. The co-administration of IDV with DRV/r resulted in increases of 24, 44 and 11% for, respectively, DRV AUC(12h), C(min) and C(max), compared with administration of DRV/r alone. Eight volunteers discontinued due to an adverse event. Overall, adverse events and laboratory abnormalities were more commonly reported during treatments including IDV.

Conclusions: When used in combination with DRV/r, dose adjustment of IDV from 800 mg b.i.d. to 600 mg b.i.d. may be warranted in cases of intolerance.