Interactions between Verapamil and Digoxin in Langendorff‐Perfused Rat Hearts: The Role of Inhibition of P‐glycoprotein in the Heart
Makaleler > Tam Makale · 2010
Yazarlar: Mualla Aylin ARICI, Mustafa Emrah KILINÇ, Omer DEMİR, Mehmet Ates, Alaattin YEŞİLYURT, Ayse Gelal
Basic & Clinical Pharmacology & Toxicology, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2010, cilt 107, ss 847-852
DOI: 10.1111/j.1742-7843.2010.00574.x
Özet
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 μg/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.