ABSTRACT
Objective: This study aimed to investigate the pharmacokinetics interaction of dapoxetine with different doses of green tea extract in healthy volunteers using midazolam (CYP3A4 probe).Method and materials: Twelve healthy males were included in a random three-way crossover study. Each volunteer received dapoxetine 60 mg and midazolam 7.5 mg concurrently after drinking 250 ml of water, 250 ml of fresh extract of 2 gram of green tea or 250 ml of fresh extract of 4 gram of green tea with one week washout period. Plasma samples were analyzed for dapoxetine and midazolam using HPLC.Results: The co-administration of dapoxetine with 4 gm green tea extract significantly increased dapoxetine AUC∞ (from 3218.74 μg.hr/L to 4207.65 μg.hr/L, P< 0.05) and dapoxetine Cmax (from 433.1 μg/L to 601.1 μg/L,P< 0.05) with a decrease in CL and t1/2 only after administration of 4 gm green tea extract. There was a significant increase in midazolam AUC∞ (from 41.123 μg.hr/L to 58.55 μg.hr/L, P< 0.05) and midazolam Cmax (from 36.07 μg/L to 53.53 μg/L,P< 0.05) with a decrease in CL and t1/2only after administration of 4 gm green tea extract. However, the intake of 2 gram green tea extract showed no significant change in either dapoxetine or midazolam AUC or Cmax (p≥0.05). Conclusion: High dose of green tea intake increases dapoxetine bioavailability by the inhibiting CYP3A4 enzyme as indicated by the change in midazolam pharmacokinetic. Taking high dose of green tea with dapoxetine should be avoided. However, normal dose of green tea is safe for dapoxetine co-administration.
ABSTRACT
Objectives: This study aimed to evaluate a new simple colorimetric method for the assay of endothelial nitric oxide synthase activity in clinical researches and to compare between the role of vanadium chloride and nitrate reductase enzyme in the assay method. Methods and materials: The new method involved using RBCs lysate to measure eNOS of the endothelium, using NADPH recycling system to enable the colorimetric measurement of eNOS, and using vanadium chloride to converting nitrate to nitrite. The method repeated again using nitrate reductase then vanadium results were compared with nitrate reductase results. The clinical study involved sixty patients who were randomly divided into two groups; group one received atorvastatin 40 mg daily, group two (control group) received placebo capsules. Patients were examined both before and after six weeks for endothelial nitric oxide synthase (eNOS) and for international index of erectile function-5 (IIEF-5) scores. Results: In comparison to nitrate reductase, vanadium showed no significant difference in eNOS activity indicating similar role and activity. However, In comparison to control group, atorvastatin showed a significant increase in eNOS (48.16% for vanadium, and 44.3% for nitrate reductase, P<0.05). Also, atorvastatin showed a significant increase in IIEF-5 score (39.16%, P<0.05) and there was a significant correlation between eNOS and IIEF-5 score (P<0.05). Conclusion: The study recommended this method for assaying eNOS using RBCs lysate, NADPH recycling system and vanadium chloride. This method is simple, reliable, and suitable for routine use in clinical researches.