Talinolol Verapamil

Talinolol, a good P-gp substrate, is eliminated from the body mainly by intestinal and renal excretion with minimal metabolism in humans. In a clinical study, a P-gp-mediated interaction between talinolol and verapamil has been reported (45). The inhibitory effect of verapamil on the intestinal secretion of talinolol was determined in six healthy volunteers by using the intestinal perfusion technique. While perfusing the small intestine with a verapamil-free solution, the mean intestinal secretion rate of talinolol was 4.0 pg/min after an intravenous dose of talinolol. The intestinal secretion rate decreased to 2.0 pg/min when a verapamil-containing solution was perfused (45). Similar to the clinical data, talinolol-verapamil interaction was also observed in rats. Coadministration of verapamil (4 mg/kg, PO) resulted in a 2.5- and 2.2-fold increase in the plasma oral AUC for S- and //-talinolol, respectively, after an oral dose of racemic talinolol in rats. On the other hand, after an intravenous dose of racemic talinolol, the inhibitory effect of verapamil on talinolol was less significant and there was only a 40% and 30% increase in AUC, respectively, for S- and //-talinolol (46). These results suggest that the larger increase in AUC of talinolol ( 2- to 2.5-fold) after oral administration was likely due to the combination of an... 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

Schwarz, U. I., Gramatte, T., Krapp-weis, J., Berndt, A., Oertel, R., von Richter, O., Kirch, W., Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans, Clin. Pharmacol. Ther. 1999, 65, 283-290. 

Gramatte, T., Oertel, R., Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil,... 

In a randomised, crossover study, a single 120-mg dose of (Kj-verapamil reduced the bioavailability of a single 50-mg dose of talinolol by 25% in 9 healthy subjects. ... 

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