Effects of Grapefruit and Pomegranate Juices on the Pharmacokinetic Properties of Dapoxetine and Midazolam in Healthy Subjects
Abstract
BACKGROUND: The package leaflet for dapoxetine, an effective treatment for premature ejaculation, includes a strict warning against coadministration with drugs or herbal remedies that strongly induce or inhibit the activity of Cytochrome P450 (CYP) 3A4 enzyme.
OBJECTIVE: To assess the effects of multiple daily consumption of grapefruit juice (GFJ) and pomegranate juice (PJ) on the pharmacokinetics of dapoxetine, we conducted an open-label, three-way crossover study in 12 healthy subjects using midazolam as a probe substrate for CYP3A4.
METHODS: Participants received a single oral dose of dapoxetine (60 mg) and midazolam (7.5 mg) after pretreatment with 250 ml of either water, undiluted GFJ, or PJ for three consecutive days. All subjects were monitored for adverse effects during the study period.
RESULTS: Compared to pretreatment with water, GFJ increased the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) and peak plasma concentration (C max) of dapoxetine by 60 and 80 %, respectively, and prolonged its elimination half-life (t 1/2) by 43 %. Similar effects of GFJ on the pharmacokinetics of midazolam were observed with a significant increase in AUC0-∞ (75 %), C max (40 %), and t 1/2 (92 %). Slight but not statistically significant changes were observed in the pharmacokinetics of dapoxetine and midazolam after pretreatment with PJ. Time to reach C max (T max) did not differ among the three phases.
CONCLUSION: These results suggest that GFJ…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 12 participants or records.
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