ORIGINAL PAPER Effect of pomegranate juice on the pharmacokinetics of nitrendipine in rabbits Swathi Voruganti • Kishore Rapolu • Santoshkumar Tota • Shravan Kumar Yamsani • Madhusudan Rao Yamsani Received: 28 September 2011 / Accepted: 10 November 2011 / Published online: 22 November 2011 Ó Springer-Verlag France 2011 Abstract Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochrome enzymes. The purpose of this study was to investigate the effect of acute and chronic PJ on the pharmacokinetics of oral nitrendipine (10 mg/kg) in rabbits. Male New Zealand rabbits were pretreated with PJ for 1 week and on the last day, a single dose of nitrendipine was given orally. In another group, both PJ and nitrendipine were co-administered to evaluate the acute effect of PJ on nitrendipine pharmacokinetics. The control group received oral distilled water for 1 week and admin- istered with nitrendipine on the last day. Blood samples were collected at different time points and nitrendipine concentration was estimated by high-performance liquid chromatography. Relative to control, the area under the concentration–time curve and peak plasma concentration of nitrendipine were 2.03- and 2-fold, respectively, greater in the PJ-pretreated group. However, co-administration of PJ had no significant effect on these parameters. Further, there was no significant change in the elimination rate constant and elimination half-life of nitrendipine in both PJ co-administered and pretreated groups in comparison with control. These results suggest that PJ inhibits the intestinal metabolism of nitrendipine without affecting hepatic metabolism in rabbits. Although this potential interaction needs to be explored further, the concomitant use of PJ and nitrendipine should be avoided. Keywords Pomegranate juice Á Nitrendipine Á Pharmacokinetics Á Food–drug interaction 1 Introduction Several fruit juices have been reported to cause food–drug interactions mainly due to the inhibition of drug-metabo- lizing enzymes (Lim et al. 2003; Bailey and Dresser 2004; Hidaka et al. 2005). Pomegranate (Punica granatum) contains a number of phytochemicals including punicala- gin, ellagic acid, gallotannins, anthocyanins, and flavo- noids (Cerda et al. 2003). It has been used in folk medicine for a wide variety of therapeutic purposes (Langley 2000). There is growing interest in this fruit because of its potential health benefits in cases of certain cancers, car- diovascular, and neurodegenerative disorders (Kim et al. 2002; Aviram et al. 2004). As noted in the United States patents section, the primary health benefits of PJ have focused on the antioxidant actions of the juice and its potential to prevent atherosclerosis as well as slow pro- gression of atherosclerotic plaques. Five small human clinical trials testing cardiovascular activities have evalu- ated PJ for its effects on cholesterol, atherosclerosis, myocardial perfusion, hypertension, and erectile dysfunc- tion (Gil et al. 2000; Kaplan et al. 2001; Aviram and Dornfeld 2001; Aviram et al. 2002, 2004; Noda et al. 2002; Sumner et al. 2005). Because of these beneficial effects, pomegranate has been increasingly popularized (Basu and S. Voruganti Á K. Rapolu Á S. K. Yamsani Á M. R. Yamsani National Facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) Centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506 009, Andhra Pradesh, India S. Voruganti (&) Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506 009, Andhra Pradesh, India e-mail: swathi_1286@yahoo.co.in S. Tota Division of Pharmacology, (CSIR) Central Drug Research Institute, Lucknow 226001, Uttar Pradesh, India 123 Eur J Drug Metab Pharmacokinet (2012) 37:77–81 DOI 10.1007/s13318-011-0075-4