The Effect of Green Tea on Sildenafil Pharmacokinetics in Egyptian Healthy Volunteers

Abstract

Aim: To investigate the interaction of slidenafil and green tea in normal healthy male volunteers using probe drugs (midazolam, CYP3A4 activity). Study Design:  Ten healthy males were included in random crossover single dose study.  Each volunteer received one tablet of sildenafil 50 mg and one tablet of midazolam 7.5 mg concurrently either after drinking 250 ml of water or 250 ml of fresh extract of 2 gram of green tea. After one week washout period, each volunteer received the other intervention. Plasma samples were analyzed for sildenafil and midazolam using HPLC. Place and Duration of Study: The Laboratory of Pharmaceutical Research Center of Faculty of Pharmacy, Tanta University, Egypt, between June to July 2013. Methodology: Blood samples were obtained after the insertion of peripheral cannula into the forearm. Samples were obtained before sildenafil and midazolam intake (blank) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 10, and 12 hours after sildenafil and midazolam administration. The samples were collected in clean heparinized tubes. Plasma was obtained by centrifugation and was stored at –20° until assay. Plasma samples were analyzed for sildenafil and midazolam using HPLC. Results: Coadministration of green tea with sildenafil tea increased the extent but not the rate of sildenafil absorption. It resulted in higher plasma concentrations (AUC∞ increased from 484.2 ± 67.27 μg hr/L to 731.5 ± 111.01 μg hr/L (90% CI 1.50 (1.36-1.66) and the Cmax from 318.9 ± 46.8 μg /L to 414.9 μg/L ± 67.0 μg/L (90% CI 1.29 (1.15-1.43). The elimination rate constant of sildenafil was significantly decreased and the elimination half life was prolonged by about 36%. However, AUC∞ of midazolam increased by 16% and Cmax by 14%; suggesting a small reduction CYP 3A4 activity. Conclusion: Increased bioavailability of sildenafil after green tea intake may be caused by the effect of catechins which can alter spontaneous activity of small intestine or an effect on transporters. Patients who are taking green tea may need smaller doses of sildenafil, and those at higher risk of developing sildenafil adverse effects and are taking green tea should seek medical advice before taking their sildenafil therapy.