This study evaluated the effect of strong inhibitors of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pharmacokinetics (PK) of rimegepant in healthy adults.

Successful management of migraine symptoms in patients with comorbid conditions can be challenging. Clinically significant drug interactions can limit the utility of medications used for the acute and preventive treatment of migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist with demonstrated efficacy and safety in the acute and preventive treatment of migraine. In vitro studies have shown that rimegepant is a substrate of P-gp and BCRP efflux transporters; current US prescribing information regarding the coadministration of rimegepant with inhibitors of these transporters is based solely on in vitro assessment.

This single-center, open-label, randomized study had 2 parts. Part 1 was a 2-period, 2-sequence, crossover evaluation of the effect of cyclosporine (single oral 200-mg dose), a strong inhibitor of both P-gp and BCRP, on the PK of rimegepant 75 mg. Part 2 was a 2-period, 2-sequence, crossover evaluation of the effect of quinidine (single oral 600-mg dose), a strong selective P-gp inhibitor, on the PK of rimegepant 75 mg.

Fifteen subjects completed Part 1; 12 subjects completed Part 2. Coadministration with cyclosporine increased rimegepant area under the curve from time zero to infinity (AUC_0-inf) and maximum plasma concentration (C_max); geometric mean ratios (90% CI) versus rimegepant alone were 160% (149, 172) and 141% (127, 157), respectively. In Part 2, the evaluation with quinidine increased rimegepant AUC_0-inf and C_max similarly; geometric mean ratios (90% CI) versus rimegepant alone were 155% (140, 172) and 167% (146, 191), respectively.

Strong P-gp inhibitors (cyclosporine, quinidine) moderately increased rimegepant exposures (>50%, <2-fold). The similar effect of cyclosporine and quinidine on rimegepant exposure suggests that BCRP inhibition minimally influences rimegepant exposure.