Background:  Generic antiretrovirals are increasingly used in resource-limited settings, often in the absence of independent pharmacokinetic, safety or efficacy testing. In this cross-over study, detailed 12-hour steady-state exposures to indinavir (IDV) obtained from a generic formulation (Inhibisam) widely used in Argentina were compared to brand IDV (Crixivan) to determine whether the 2 formulations afforded similar exposures.

Methods:  Steady-state pharmacokinetic profiles were obtained for 10 patients receiving a 2-daily regimen consisting of 2 NRTI plus IDV/ritonavir (RTV) (800/100 mg). Five patients were initially prescribed generic IDV while 5 were receiving Crixivan. Blood samples were taken immediately prior to the morning dose of IDV/RTV and then at 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose. Patients were then switched to receive the alternative formulation of IDV and the pharmacokinetic were reassessed in the same way. Plasma IDV concentrations were determined by a validated assay utilizing high performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters (C_trough [12 hour post dose], C_max, AUC^0-12) were compared by parametric and non-parametric methods.

Results:  On 10 patients, 20 evaluations were conducted. All had completed >24 weeks of successful combination therapy (plasma viral load <50 copies/mL). The IDV C_trough, C_max and AUC^0-12 were not significantly different for the two sources of IDV (see table below). Plasma HIV RNA remained <50 copies/mL at the time of the second pharmacokinetic assessment for all patients.