Evaluating the Clearance of Common Extra-label Drug Combinations by Turkey Hepatocytes in Primary Culture
Although common in the commercial turkey industry, concurrent use of two or more drugs in the same feed can result in drug-drug interactions that may impact drug clearance. Therefore, this thesis tested the hypothesis that primary turkey hepatocyte cultures are useful as a high-throughput in vitro model to screen for drug-drug interactions with drug combinations in poultry feed. The cultures were validated by confirming the presence of proteins, enzymes, and enzyme processes that are involved in drug clearance. The in vitro model was successfully used to monitor the clearance of fenbendazole and monensin and to assess differences in the rates of clearance when the drugs were used alone versus in combination. Linear regression analysis revealed that the rate of clearance of fenbendazole in combination was 13.3% slower than fenbendazole clearance on its own. Additional experiments are needed to determine the clinical and human food safety relevance of the observed interaction.