Evaluation of the drug–drug interaction potential for trazpiroben (TAK-906), a D₂/D₃ receptor antagonist for gastroparesis, towards cytochrome P450s and transporters

Trazpiroben (TAK-906), a peripherally selective dopamine D2/D3 receptor antagonist, is being developed for the treatment of patients with gastroparesis. The potential trazpiroben to act as perpetrator or victim cytochrome P450 (CYP)- transporter- mediated drug–drug interactions (DDIs) was evaluated following latest regulatory guidelines.In vitro studies revealed that metabolised mainly through non-CYP pathway (56.7%) by multiple cytosolic, NADPH-dependent reductase, such aldo-keto reductase and short-chain dehydrogenase/reductase including carbonyl reductases. Remaining metabolism occurs CYP3A4 CYP2C8 (43.3%). neither an inhibitor nor inducer major CYP enzymes at clinically relevant dose. It substrate P-glycoprotein (P-gp) organic anion transporting polypeptide (OATP) 1B1/1B3, but not transporters listed in DDI guidelines This consistent findings from CYP3A P-gp-based clinical assessment showing no substantial change (≤2-fold) exposure when co-administered itraconazole.Collectively, has low enzyme-mediated DDIs unlikely transporter-mediated there may be OATP1B1/1B3 will clinically.