Bioavailability of Generic Ritonavir and Lopinavir/Ritonavir Tablet Products in a Dog Model

In this study, we explored the bioavailability in dogs and chemical potency of generic ritonavir and lopinavir/ritonavir tablet products manufactured by various pharmaceutical companies. Chemical potency of the products was examined by HPLC quantitation of ritonavir and lopinavir. Using a dog model, we determined point estimates for Cmax and AUC of ritonavir and lopinavir/ritonavir for eight generic products compared to Abbott's Norvir® capsule and Kaletra® tablet. Chemical potencies ranged from 79.0% to 104.6%. Point estimates for AUC in the generic tablet products ranged from 0.01 to 1.11, indicating that the relative bioavailability of these formulations was in the range of 1-111% compared to the branded products. This study showed significant variability in bioavailability in a dog model amongst generic tablet products containing the protease inhibitors ritonavir or lopinavir/ritonavir. The chemical potency of the generic products was not indicative of the plasma levels of ritonavir or lopinavir that were achieved. These results reinforce the need for human bioequivalence testing of generic products containing ritonavir or lopinavir/ritonavir to assure that efficacy in patients is not compromised prior to these products being made available to patients. Procurement policies of funding agencies should require such quality assurance processes. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:626-631, 2010