Pharmacokinetics interaction of dapoxetine with different doses of green tea extract in male healthy volunteers using midazolam as CYP3A4 enzyme probe.

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.