Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil

Objective: To examine the secretion of the beta(1)-adrenergic receptor anta gonist talinolol into the small intestine during its intravenous administra tion and to show the relevance of the P-glycoprotein-modulating drug verapa mil for this secretory transport mechanism in humans. Methods: In six healthy volunteers the intestinal steady-state perfusion te chnique (triple lumen tubing system) was used for measuring the appearance of talinolol within the small intestine while the drug was infused intraven ously. During four of the seven perfusions performed, the perfusion fluid w as changed from a verapamil-free solution and talinolol appearance was meas ured while a R-verapamil-containing solution (565 mu mol/L) was perfused. Results: Talinolol was transported into the intestinal lumen up to a concen tration gradient between lumen and blood of about 5.5:1, While perfusing th e small intestine with a verapamil-free solution, the intestinal secretion rate of talinolol ranged from 1.94 to 6.62 mu g/min per 30 cm length of the intestine (median values). Perfusion of a R-verapamil-containing perfusion fluid resulted in lower secretion rates (0.59 to 3.71 mu g/30 cm . min), c orresponding to 29% to 56% of the values obtained without verapamil supplie d intraluminally. Conclusion: Intravenously administered talinolol is actively secreted into the human small intestine. This secretion is reduced by the intraluminal su pply of the P-glycoprotein modulating drug R-verapamil. This gives further rationale for P-glycoprotein-mediated intestinal drug secretion as a cause for incomplete oral bioavailability and for drug interactions during intest inal absorption.