CAM2038, FluidCrystal injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research was to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model was developed for CAM2038 based on the previously published buprenorphine PBPK model after intravenous and sublingual administration and the PK profiles after subcutaneous administration of CAM2038 from 2 phase I clinical trials. The strong CYP3A4 inhibitor ketoconazole was predicted to increase the buprenorphine exposure by 35% for the Q1W formulation and 34% for Q4W formulation, respectively. Also, the strong CYP3A4 inducer rifampin was predicted to decrease the buprenorphine exposure by 26% for both the Q1W and Q4W formulations. The results provided insight into the potential DDI effect for CAM2038 and suggested a lack of clinically meaningful DDI when CAM2038 is coadministered with CYP3A4 inhibitor or inducer. Therefore, no dose adjustment is required when CAM2038 is coadministered with CYP3A4 perpetrators.
Keywords: buprenorphine; drug-drug interaction; ketoconazole; physiologically based pharmacokinetics; rifampin.
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