Effects of Grapefruit and Pomegranate Juices on the Pharmacokinetic Properties of Dapoxetine and Midazolam in Healthy Subjects

Abdlekawy, Khaled S.; Donia, Ahmed M.; Elbarbry, Fawzy

doi:10.1007/s13318-016-0352-3

Cited by 25 publications

(10 citation statements)

References 26 publications

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“…Based on our study results, co‐administration of GFJ and PJ with BRX raised the absorption of BRX in Sprague–Dawley rats while TJ did not show a similar effect. Additionally, according to Abdlekawy et al, GFJ has the potential to inhibit hepatic CYP3A4 enzymes (Abdlekawy et al, 2017), which was not evident in our investigation as the T max and t 1/2 were not significantly altered by the administration of any juice. The inference from the above findings is that concomitant use of GFJ and PJ with treatment with BRX should be avoided or dose adjustment should be advised.…”

Section: Resultscontrasting

confidence: 67%

“…Contrary to this, in the literature, many fruits juices have been recorded to influence drug metabolism and transport and lead to clinically significant fruit juice–drug interactions (FDI) (Won et al, 2012). For instance, grapefruit juice (GFJ) can cause FDI with many drugs like midazolam, simvastatin and fexofenadine through inhibition of intestinal as well as hepatic CYP3A4 enzymes and/or efflux by P‐glycoprotein or uptake by organic anion transporting polypeptide transporters (Abdlekawy et al, 2017; Bailey, 2010; Dresser et al, 2005; Won et al, 2012). Like GFJ, pomegranate juice (PJ) and tomato juice (TJ) also have the potential to inhibit CYP3A4 enzymes in the body (Ohkubo et al, 2017; Srinivas, 2013; Won et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the impact of grapefruit juice, pomegranate juice and tomato juice on pharmacokinetics of brexpiprazole in rats using UHPLC–QTOF–MS

Thakkar

Sahu

Rathod

et al. 2021

Biomedical Chromatography

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Brexpiprazole (BRX) is approved for the treatment of schizophrenia and major depressive disorders and it is mainly metabolized by CYP3A4 and CYP2D6. Grapefruit juice (GFJ), pomegranate juice (PJ) and tomato juice (TJ) have the potential to inhibit CYP3A4 enzymes in the body. However, fruit juice–drug interactions between BRX and GFJ, PJ and TJ have not been studied extensively. The present study describes the influence of GFJ, PJ and TJ on the pharmacokinetic parameters of BRX in rats. The study samples were analyzed using a mass‐accurate and single‐step bioanalytical method by ultra‐high‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry over a wide calibration range of 20–1,500 ng/ml. The results of the pharmacokinetic study denoted that the combined administration of GFJ and PJ could increase systemic exposure of BRX. The area under the curve of BRX increased 3.43‐ and 1.88‐fold with co‐administration of GFJ and PJ, respectively, while TJ with BRX had no effect on the area under the curve. Time to peak concentration and half‐life were not significantly changed by any juice co‐administration. The results show that GFJ and PJ affect the pharmacokinetic profile of BRX and hence advice needs to be given to patients.

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Section: Resultscontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Investigation of the impact of grapefruit juice, pomegranate juice and tomato juice on pharmacokinetics of brexpiprazole in rats using UHPLC–QTOF–MS

Thakkar

Sahu

Rathod

et al. 2021

Biomedical Chromatography

View full text Add to dashboard Cite

show abstract

“…As an example, pomegranate juice significantly inhibits CYP2C9 and CYP3A4 in preclinical models [223]. However, 5 human clinical trials do not confirm this inhibition [76,80,224,225]. Similarly, in vitro inhibition of CYP3A4 by coffee does not have an impact on felodipine pharmacokinetics, a CYP3A4 probe, in healthy volunteers [81].…”

Section: Relevance and Limitations Of Animal Assaysmentioning

confidence: 99%

Potential cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments

Gougis

Hilmi

Géraud

et al. 2021

Critical Reviews in Oncology/Hematology

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“… 39 However, there is little clinical concern as the data in health volunteers shows little effect of pomegranate juice on the pharmacokinetics of CYP metabolized drugs, while grapefruit juice does affect the clearance of those drugs. 40 …”

Section: What Should Physicians Tell Prostate Cancer Patients About Pmentioning

confidence: 99%

A review of pomegranate in prostate cancer

Paller

Pantuck

Carducci

2017

Prostate Cancer Prostatic Dis

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BackgroundPreclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials.MethodsTrials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC).ResultsIn the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-OHdG, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs. the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multi-component food supplement tablet, including 31.25% pomegranate extract, found significant slowing of PSA increase in the food supplement arm vs. placebo in men on active surveillance and those experiencing biochemical recurrence.ConclusionsPomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multi-component food supplement showed promising results in a phase II study in active surveillance and BCR patients.

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Effects of Grapefruit and Pomegranate Juices on the Pharmacokinetic Properties of Dapoxetine and Midazolam in Healthy Subjects

Cited by 25 publications

References 26 publications

Investigation of the impact of grapefruit juice, pomegranate juice and tomato juice on pharmacokinetics of brexpiprazole in rats using UHPLC–QTOF–MS

Investigation of the impact of grapefruit juice, pomegranate juice and tomato juice on pharmacokinetics of brexpiprazole in rats using UHPLC–QTOF–MS

Potential cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments

A review of pomegranate in prostate cancer

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