The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers

Bedada, Satish Kumar; Boga, Praveen Kumar

doi:10.1007/s00228-016-2173-3

Cited by 24 publications

(18 citation statements)

References 34 publications

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“…This was observed trough increased C max , AUC, T 1/2 and decreased K el and CL/F of chlozoxazone when administered with piperine. The same authors [179] found very similar effect of piperine intake to bioavailibility of fexofenadine, where piperine treatment significantly increased C max of fexofenadine and AUC time curve, as well as decreased CL/F of this drug. A 3-fold increase in C max and 1.5-fold increase in AUC were found for tetrahydrocannabinol, while a 4-fold increase in C max and a 2.2-fold increase in AUC were observed for cannabidiol when co-administered with piperine [159].…”

Section: Effect Of Piperine On Oral Bioavailability Of Drugs and Natumentioning

confidence: 71%

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

et al. 2019

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Piperine is the main compound present in black pepper, and is the carrier of its specific pungent taste, which is responsible for centuries of human dietary utilization and worldwide popularity as a food ingredient. Along with the application as a food ingredient and food preservative, it is used in traditional medicine for many purposes, which has in most cases been justified by modern scientific studies on its biological effects. It has been confirmed that piperine has many bioactive effects, such as antimicrobial action, as well as many physiological effects that can contribute to general human health, including immunomodulatory, hepatoprotective, antioxidant, antimetastatic, antitumor, and many other activities. Clinical studies demonstrated remarkable antioxidant, antitumor, and drug availability-enhancing characteristics of this compound, together with immunomodulatory potential. All these facts point to the therapeutic potential of piperine and the need to incorporate this compound into general health-enhancing medical formulations, as well as into those that would be used as adjunctive therapy in order to enhance the bioavailability of various (chemo)therapeutic drugs.

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Section: Effect Of Piperine On Oral Bioavailability Of Drugs and Natumentioning

confidence: 71%

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

et al. 2019

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“…In Caco‐2 cells, the transport of digoxin and cyclosporine A, which is mediated by P‐gp, was inhibited by piperine with IC 50 values of 15.5 and 74.1 μM, respectively . Piperine was found to be associated with elevated maximum plasma concentration (C max ) and area under the curve (AUC) values of fexofenadine (a P‐gp substrate), thus decreasing the drug's total clearance . It was found to inhibit CYP3A enzyme mediated metabolism of triazolam to triazolam‐1′‐hydroxylation in a noncompetitive inhibition model .…”

Section: Introductionmentioning

confidence: 99%

Characterization of stable and reactive metabolites of piperine formed on incubation with human liver microsomes

et al. 2019

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Black pepper, though commonly employed as a spice, has many medicinal properties.It consists of volatile oils, alkaloids, pungent resins, etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, β-unsaturated carbonyl group (Michael acceptor), and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed on in vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz, glutathione (GSH) and N-acetylcysteine (NAC). The samples were analysed by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) using Thermo Scientific Q Exactive Plus Orbitrap. Full scan MS followed by data-dependent MS 2 (Full MS-ddMS 2 ) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a-c, M2a-b, M3a-c, and M4a-b) were detected. Their formation involved removal of carbon (3, M1a-c), hydroxylation (2, M2a-b), hydroxylation with hydrogenation (3, M3a-c), and dehydrogenation (2, M4a-b). Out of these metabolites, M1, M2, and M3 are reported earlier in the literature, but their isomers and two M4 variants are novel. In addition, six novel conjugates of RMs, including three GSH conjugates of m/z 579 and three NAC conjugates of m/z 435, were also observed.

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“…The doses of PIP used in the rats were 5 and 10 mg/kg which were adopted from another study for adult rats ( Malini et al, 1999 ). The doses of PIP in the present study may be clinically relevant, since PIP in clinic trials has been tested for its potential to affect bioavailability of other compounds in food and dietary supplements and the dose of PIP used was 20 mg for humans ( Shoba et al, 1998 ; Bedada and Boga, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell Development but Inhibiting Spermatogenesis in Rats

Chen

Liu

et al. 2018

Front. Pharmacol.

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Background: Piperine is the primary pungent alkaloid isolated from the fruit of black peppercorns. Piperine is used frequently in dietary supplements and traditional medicines. The objective of the present study was to investigate the effects of piperine on the testis development in the pubertal rat.Methods: Piperine (0 or 5 or 10 mg/kg) was gavaged to 35-day-old male Sprague-Dawley rats for 30 days. Serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The development of adult Leydig cell population was also analyzed 65 days postpartum. For in vitro studies, immature Leydig cells were isolated from 35-day-old male rats and treated with 50 μM piperine in the presence of different steroidogenic stimulators/substrates for 24 h.Results: Thirty-day treatment of rats with piperine significantly increased serum T levels without affecting LH concentrations. However, piperine treatment reduced serum FSH levels. Consistent with increase in serum T, piperine increased Leydig cell number, cell size, and multiple steroidogenic pathway proteins, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, 17α-hydroxylase/20-lyase, and steroidogenic factor 1 expression levels. Piperine significantly increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phosphos-AKT2 (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Interestingly, piperine inhibited spermatogenesis. Piperine in vitro also increased androgen production and stimulated cholesterol side-chain cleavage enzyme and 17α-hydroxylase/20-lyase activities in immature Leydig cells.Conclusion: Piperine stimulates pubertal Leydig cell development by increasing Leydig cell number and promoting its maturation while it inhibits spermatogenesis in the rat. ERK1/2 and AKT pathways may involve in the piperine-mediated stimulation of Leydig cell development.

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The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers

Cited by 24 publications

References 34 publications

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

Characterization of stable and reactive metabolites of piperine formed on incubation with human liver microsomes

Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell Development but Inhibiting Spermatogenesis in Rats

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