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

被引:8
作者
Arici, Mualla Aylin
Kilinc, Emrah [2 ]
Demir, Omer
Ates, Mehmet [3 ]
Yesilyurt, Alaattin [2 ]
Gelal, Ayse [1 ]
机构
[1] Dokuz Eylul Univ, Fac Med, Dept Pharmacol, Sch Med, TR-35340 Izmir, Turkey
[2] Ege Univ, Fac Pharm, Dept Analyt Chem, Izmir, Turkey
[3] Dokuz Eylul Univ, Adv Profess Sch Hlth Sci, TR-35340 Izmir, Turkey
关键词
BINDING CASSETTE TRANSPORTERS; DRUG-DRUG INTERACTIONS; IN-VITRO; PHARMACOKINETICS; QUINIDINE; MICE;
D O I
10.1111/j.1742-7843.2010.00574.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:847 / 852
页数:6
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