Interactions between Verapamil and Digoxin in Langendorff-Perfused Rat Hearts: The Role of Inhibition of P-glycoprotein in the Heart


ARICI M. A. , Kilinc E. , DEMİR O., Ates M., YEŞİLYURT A., Gelal A.

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, vol.107, no.5, pp.847-852, 2010 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 107 Issue: 5
  • Publication Date: 2010
  • Doi Number: 10.1111/j.1742-7843.2010.00574.x
  • Title of Journal : BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
  • Page Numbers: pp.847-852

Abstract

P-glycoprotein (P-gp) is expressed in tumour cells as well as normal tissues including heart. Modulation of P-gp transport in vivo may lead to increased drug penetrance to tissues with resulting increases in toxicity. We aimed to investigate the effects of P-gp on the isolated heart by digoxin infusion in the absence and presence of verapamil. The study was performed in Langendorff isolated perfused rat hearts. After a 20 min. stabilisation period with Tyrode Buffer, digoxin (125 mu g/5 mL) was infused for 10 min. in the control group (n = 7). The same dose of digoxin was infused during perfusion with verapamil (1 nm) containing Tyrode Buffer (n = 8) in the study group. Outflow concentration and cardiac parameters of digoxin were measured at frequent intervals for 40 min. AUEC((0-40 min)) for left ventricular developed pressure was significantly increased in the presence of verapamil (4260 +/- 39.37 mmHg min versus 4607 +/- 98.09 mmHg min; 95% CI -587.7 to -105.8; p = 0.0083). The significant increases in left ventricular developed pressure were at 20, 25, 30, 35 and 40 min. AUC((0-40 min)) value for outflow digoxin concentration-time curve was significantly lower in the presence of verapamil. Verapamil increased the positive inotropic effect of digoxin, probably through the inhibition of P-gp, which effluxes digoxin out of cardiac cells.