BASIC AND CLINICAL PHARMACOLOGY AND TOXICOLOGY, vol.1, no.105, pp.73, 2009 (SCI-Expanded)
THE EFFECTS OF P-GLYCOPROTEIN INHIBITION ONDIGOXIN PHARMACODYNAMICS IN ISOLATED RATHEARTSArici A.1,KilincE.2,DemirO.1,AtesM.3, Gelal A.11Department of Pharmacology, Faculty of Medicine, Dokuz Eylul Uni-versity, Izmir, Turkey;2Department of Analytical Chemistry, Ege Univer-sity Pharmacy Faculty, Izmir, Turkey;3Advanced Professional School ofHealth Sciences, Faculty of Medicine, Dokuz Eylul University, Izmir,TurkeyIntroduction:P-glycoprotein (P-gp) is expressed in tumor cells as wellas normal tissues including heart. In some cases of atrial fibrilationdigoxin which is a P-gp substrate is used in combination with verapamil.Clinical experience suggests that verapamil may increase digoxin toxicitythrough inhibition of P-gp activity resulting in a decreased renal elimina-tion. We aimed to investigate the effects of P-gp on the isolated heart bydigoxin infusion in the absence and presence of verapamil.Materials and Methods:The study was performed in Langendorff iso-lated perfused rat hearts. After 20 min stabilization period with Tyrodebuffer, digoxin (25lg) was infused for 10 min in control group (n = 8).Same dose digoxin was infused during perfusion with verapamil (1 nM)containing Tyrode buffer (n = 8) in the study group. Coronary perfusionpressure (CPP), Left Ventricular Developed Pressure (LVDP), maximumrates of LVP development (dp/dtmax) and Heart Rate (HR) were recordedfor 40 min. The area under effect curve during the first 40 min (AUEC0–40 min) was calculated by linear trapezoidal method.Results:AUEC0-40 minfor LVDP was significantly increased by verap-amil (4260 ± 39.37 vs. 4607 ± 98.09; %95 CI -587.7 to -105.8;P = 0.0083). The significant increases in LVDP were at 20, 25, 30, 35and 40 min. However, the increase in the dp/dtmaxwas only significantat 40 min.Conclusion:The enhancement of LVDP in the rat hearts perfused byverapamil could be due to decrease in P-gp mediated efflux of digoxin.