Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment

Ren, Tianjing; Yang, Mengxue; Xiao, Min; Zhu, Junjie; Xie, Wen; Zuo, Zhong

doi:10.1016/j.lfs.2018.12.060

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…For instance, piperine (Lee et al, 2018), ginger resin (Markam et al, 2019) and glycyrrhizic acid (Selyutina and Polyakov, 2019) have successfully been used to increase the bioavailability of various drugs. Piperine (PPR), a golden yellow and needle shaped alkaloidal material derived from black pepper, has been documented to inhibit the CYP3A4 drugmetabolizing enzyme and plays an important role in drug absorption and disposition (Ren et al, 2019). Ginger, the rhizome of Zingiber officinale contains 6-gingerol and 6-shogaol, is commonly used for the prevention of diarrhea and other stomach disorders (Simon et al, 2020, Nikkhah Bodagh et al, 2019.…”

Section: Introductionmentioning

confidence: 99%

Piperine phytosomes for bioavailability enhancement of domperidone

Islam

Irfan

Hussain

et al. 2021

Journal of Liposome Research

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The markedly low oral bioavailability of domperidone (anti-emetic drug) is associated with rapid first-pass metabolism in the intestine and liver. To counteract such affects, there is a need to devise a strategy to enhance absorption and subsequently bioavailability. Thus, the current study was aimed at synthesizing phytosomes consisting of phosphatidylcholine and piperine (a Pglycoprotein inhibitor). Phytosomes were prepared by salting-out method. The developed phytosomes were extensively characterized for size, zeta potential, polydispersity index, entrapment efficiency (EE %), infrared spectroscopy, X-ray diffraction, in-vitro drug release, exvivo permeation, in-vivo pharmacokinetic and toxicity. The engineered formulations of phytosomes with piperine exhibited a significant improvement in oral bioavailability of domperidone (79.5%) in comparison with the pure drug suspension under the same conditions. Pharmacokinetic parameters such as maximal plasma concentration (Cmax) and the plasma concentration (estimated from area under the curve; AUC) of domperidone have been greatly increased relative to drug alone. The improved drug absorption was attributed to inhibition of Pglycoprotein transporter. The findings of current research work suggest that the optimized phytosomes based drug delivery containing phytochemicals as bioenhancers have the potential to improve bioavailability of poorly bioavailable drugs that are substrate to P-glycoprotein.

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Section: Introductionmentioning

confidence: 99%

Piperine phytosomes for bioavailability enhancement of domperidone

Islam

Irfan

Hussain

et al. 2021

Journal of Liposome Research

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“…PIP consumption has been reported to inhibit various metabolic enzymes including CYP3A4, UDP-glucronyl transferase, UDP-glucose dehydrogenase, cytochrome BS, and aryl hydrocarbon hydroxylase. The pharmacokinetics of PIP could enhance the bioavailability of several other drugs/compounds when they are co-treated with PIP, including ciprofloxacin, resveratrol, carbamazepine, metronidazole, silybin, oxytetracycline, and phenytoin [ 10 , 14 , 15 ]. In addition, PIP co-treatment increases the anti-inflammatory efficiency and membrane permeability of resveratrol [ 16 ] and improves the serum half-life of coenzyme Q10 and β-carotene [ 17 , 18 ].…”

Section: Pharmacokinetic and Pharmacodynamic Properties Of Pipmentioning

confidence: 99%

“…Besides, the use of PIP as a sub-therapeutic agent or therapy enhancer revealed another chapter for PIP importance. Co-treatment of PIP and carbamazepine in epilepsy patients showed a significant increase in carbamazepine bioavailability, absorption, and AUC and reduced elimination half-life [ 15 , 64 ].…”

Section: Pip In Neurological and Psychiatric Diseasesmentioning

confidence: 99%

“…Altogether, the bioavailability enhancing property and the other pharmacological activities of PIP, and its metabolites have made them a hot target compound in recent research. Given the importance of these facts, several recent reviews have documented PIP and its metabolite’s different therapeutic aspects [ 13 , 14 ]; pharmacokinetic properties and medicinal chemistry [ 1 ]; and different pharmacological properties like anti-diabetic [ 15 ], anti-cancer [ 16 , 17 ], and autophagy regulation [ 18 ], as well as provided recent updates in PIP chemistry and new formulations [ 1 , 19 ]. Synthesizing this knowledge and present research context, the current review has attempted to summarize PIP effects on the prevention/treatment of different neurological and psychiatric diseases, with an emphasis on its pharmacokinetic properties.…”

Section: Introductionmentioning

confidence: 99%

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Piperine and Its Metabolite’s Pharmacology in Neurodegenerative and Neurological Diseases

et al. 2022

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Piperine (PIP) is an active alkaloid of black and long peppers. An increasing amount of evidence is suggesting that PIP and its metabolite’s could be a potential therapeutic to intervene different disease conditions including chronic inflammation, cardiac and hepatic diseases, neurodegenerative diseases, and cancer. In addition, the omnipresence of PIP in food and beverages made this compound an important investigational material. It has now become essential to understand PIP pharmacology and toxicology to determine its merits and demerits, especially its effect on the central nervous system (CNS). Although several earlier reports documented that PIP has poor pharmacokinetic properties, such as absorption, bioavailability, and blood–brain barrier permeability. However, its interaction with metabolic enzyme cytochrome P450 superfamily and competitive hydrophobic interaction at Monoamine oxide B (MAO-B) active site have made PIP both a xenobiotics bioenhancer and a potential MAO-B inhibitor. Moreover, recent advancements in pharmaceutical technology have overcome several of PIP’s limitations, including bioavailability and blood–brain barrier permeability, even at low doses. Contrarily, the structure activity relationship (SAR) study of PIP suggesting that its several metabolites are reactive and plausibly responsible for acute toxicity or have pharmacological potentiality. Considering the importance of PIP and its metabolites as an emerging drug target, this study aims to combine the current knowledge of PIP pharmacology and biochemistry with neurodegenerative and neurological disease therapy.

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“…Pepper has physiological effects owing to its antimicrobial, anti-inflammatory, detoxifying, and anti-allergic properties [16][17][18][19]. Piperine, the representative component of pepper, has various physiological activities including antitumor, antioxidant, and anti-epileptic effects [20][21][22]. Additionally, recent studies have shown that mitogen-activated protein kinases (MAPKs) and activator protein (AP)-1 are strongly involved in inflammation via up-regulation of iNOS expression and nitrite production in RAW 264.7 cells [23,24].…”

Section: Introductionmentioning

confidence: 99%

Green Pepper (Piper nigrum L.) Extract Suppresses Oxidative Stress and LPS-Induced Inflammation via Regulation of JNK Signaling Pathways

Kim

Shin

et al. 2020

Applied Sciences

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In this study, we compared the physicochemical properties and the antioxidant capacities of black and green pepper. Green pepper from India (GPI) and Sri Lanka (GPS) had higher Hunter L* and b* values and lower a* values than black pepper from India (BPI) and Sri Lanka (BPS). The contents of chlorophyll a and b, flavonoids, and phenolic compounds in GPI and GPS were higher than those in BPI and BPS. The peppercorns showed the following decreasing order of 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging capacities: GPI > GPS > BPI > BPS. High-performance liquid chromatography showed that the highest piperine content was present in GPI (8613.27 ± 45.86 mg/100 g). We further investigated the anti-inflammatory capacity of the green pepper. GPS and GPI significantly suppressed lipopolysaccharide (LPS)-induced nitrite production and inducible nitric oxide synthase expression without being cytotoxic to RAW 264.7 cells. GPS and GPI also suppressed the LPS-induced phosphorylation of mitogen-activated protein kinases, but not p65. GPS had a higher inhibitory effect on LPS-induced c-Jun phosphorylation and translocation from the cytosol to the nucleus than GPI. Thus, the findings of our study suggest that green pepper has the potential to be an effective nutraceutical against oxidative and inflammatory stress.

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Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment

Cited by 13 publications

References 41 publications

Piperine phytosomes for bioavailability enhancement of domperidone

Piperine phytosomes for bioavailability enhancement of domperidone

Piperine and Its Metabolite’s Pharmacology in Neurodegenerative and Neurological Diseases

Green Pepper (Piper nigrum L.) Extract Suppresses Oxidative Stress and LPS-Induced Inflammation via Regulation of JNK Signaling Pathways

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