The putative P‐gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P‐glycoprotein expressing cell line MDCK II MDR 1

Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P‐glycoprotein (P‐gp, ABCB 1) substrate. We wished to evaluate in vitro whether co administration of a P‐gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR 1 monolayers were measured in the absence and presence of the putative P‐gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral‐to‐apical transepithelial efflux across the MDCK II MDR 1 monolayers with a permeability of 5.7 × 10 −5  cm sec −1 compared to an apical to basolateral permeability of 1.3 × 10 −5  cm sec ‐1 . The efflux could be inhibited with the P‐gp inhibitor zosuquidar. Zosuquidar (0.4  μ mol/L) reduced the efflux ratio ( P B‐A / P A‐B ) for verapamil 4.6–1.6. The presence of telmisartan, however, only caused a slight reduction in P‐gp‐mediated verapamil transport to an efflux ratio of 3.4. Overall, the results of the present in vitro approach indicate, that clinical use of telmisartan as a P‐gp inhibitor may not be an effective strategy for increasing brain uptake of verapamil by co‐administration with telmisartan.