Planning and Evaluation of Bioequivalence Studies of Lopinavir/Ritonavir Preparations

Issues with planning bioequivalence studies of lopinavir/ritonavir (LPV/RTV) preparations are discussed. LPV is an antiviral (HIV) medicine and HIV protease inhibitor that was developed in a fixed-dose combination with RTV. According to existing RF legislation, results from bioequivalence studies with a reference drug must be submitted to register generics. Protocols and reports of bioequivalence studies of LPV/RTV film-coated tablet dosage forms that were submitted for review to the SCEEMP, MHRF, are analyzed. The number of administered tablets and duration of sample collection differed slightly in the study designs. The number of volunteers included in the study differed more substantially and was calculated based on the intra-subject coefficient of variation of LPV/RTV. A search of the internet for data on the variability of LPV/RTV found several results indicating that LPV/RTV was highly variable (30%). Recommendations for planning bioequivalence studies of LPV/RTV preparations are formulated based on the analysis.