P-glycoprotein inhibitor erythromycin increases oral bioavailability of talinolol in humans

Objective: Increased bioavailability of the beta-glycoprotein (Pgp) substra tes digoxin and cyclosporin due to erythromycin has been observed in vivo. The aim of the present study was to investigate the effect of orally admini stered erythromycin on the oral bioavailability of the beta-blocker talinol ol. Talinolol is a suitable model compound for Pgp drug-drug interaction st udies due to its Pgp-related active intestinal secretion and lack of any si gnificant metabolism. Methods: In a randomized crossover study, the oral ph armacokinetics of talinolol (50 mg) after a concomitant single oral dose of erythromycin (2 g) or placebo were investigated in 9 healthy men. Concentr ations of talinolol were measured in serum and urine by HPLC. Results: The area under the curve of talinolol serum concentrations from 0 to 24 h (AUC( (0-24))) and the maximum serum concentrations (C-max) were significantly in creased after administration of erythromycin compared to placebo. t(max) va lues were significantly reduced. The renal clearance (CLR) of talinolol was unchanged after co-administration of erythromycin and there was a small bu t statistically significant decrease in elimination half-life (t(1/2)) Seru m pharmacokinetics correlate with the results derived from urine concentrat ion measurement. One subject suffered from moderate diarrhea after erythrom ycin and was excluded from the analysis. Conclusion: We suggest that the in crease in oral bioavailability of talinolol after concomitant erythromycin is caused by increased intestinal net absorption due to Pgp inhibition by e rythromycin.