Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers

Shahnaz, Gul; Raina, Rashmi Kaul; Zutshi, U; Bedi, K. L.; Johri, R.K.; Sharma, Shrestha

doi:10.1007/bf00314996

Cited by 186 publications

(96 citation statements)

References 6 publications

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“…With regard to the effect of piperine or black pepper on drug disposition in humans, there are only very limited data. Administration of piperine significantly increased plasma concentrations of rifampin, phenytoin, propranolol, and theophylline in humans (Zutshi et al, 1985;Bano et al, 1987Bano et al, , 1991. Very recently, it was shown that a single administration of 1 g of black pepper more than doubled area under the plasma concentrationtime curve and elimination half-life of phenytoin (Velpandian et al, 2001).…”

mentioning

confidence: 99%

Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4

Bhardwaj

Glaeser²,

Becquemont³

et al. 2002

J Pharmacol Exp Ther

431

297

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Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that piperine, a major component of black pepper, inhibits drugmetabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans. However, there are no direct data whether piperine is an inhibitor of human Pglycoprotein and/or CYP3A4. We therefore investigated the influence of piperine on P-glycoprotein-mediated, polarized transport of digoxin and cyclosporine in monolayers of Caco-2 cells. Moreover, by using human liver microsomes we determined the effect of piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC 50 values of 15.5 and 74.1 M, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K i values of 36 Ϯ 8 (liver 1)/49 Ϯ 6 (liver 2) and 44 Ϯ 10 (liver 1)/77 Ϯ 10 M (liver 2), respectively. In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.Several dietary constituents and phytochemicals are now identified as important factors affecting drug disposition

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mentioning

confidence: 99%

Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4

Bhardwaj

Glaeser²,

Becquemont³

et al. 2002

J Pharmacol Exp Ther

431

297

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“…Moreover, high dose is needed for efficacy which will lead to adverse events. Pepper caused two fold increases in bioavailability of propranolol by inhibiting its metabolism by the liver and thereby excellent antihypertensive effect was obtained with low dose of propranolol (Bano et al, 1991). Similar results were also obtained when piperine was administered along with theophylline, an antiasthmatic drug and phenytoin, an anti-epileptic drug and these were due to inhibition of biotransforming enzymes in liver as well as slowing down the elimination rate (Bano et al, 1978;Bano et al, 1991).…”

Section: Solubilizer Attachmentmentioning

confidence: 54%

“…Pepper caused two fold increases in bioavailability of propranolol by inhibiting its metabolism by the liver and thereby excellent antihypertensive effect was obtained with low dose of propranolol (Bano et al, 1991). Similar results were also obtained when piperine was administered along with theophylline, an antiasthmatic drug and phenytoin, an anti-epileptic drug and these were due to inhibition of biotransforming enzymes in liver as well as slowing down the elimination rate (Bano et al, 1978;Bano et al, 1991). Piperine coadministered with a formulation containing rifampicin, pyrazinamide and isoniazid has been tested in human volunteers where, the comparative levels and peak concentration of these drugs were higher in the presence of piperine.…”

Section: Solubilizer Attachmentmentioning

confidence: 99%

Molecular targets of pepper as bioavailability enhancer

Gohil¹,

Mehta²

2009

Oriental Pharmacy and Experimental Medicine

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SUMMARYBlack pepper (family Piperaceae), is called king of spices because it is one of the oldest spice and alone accounts for about 35% of the world's total spice trade. The pepper is used in Ayurvedic medicine for the treatment of various ailments particularly neurological, broncho-pulmonary and gastrointestinal disorders. Pepper has also been reported to have various pharmacological actions but recently, it is highlighted as a bioavailability enhancer. This results in higher plasma concentration of drugs, nutrients, ions and other xenobiotics, rendering them more bioavailable for physiological as well as pharmacological actions in the body. Numerous scientific studies reported that piperine; a main bioactive compound of pepper, is responsible for its bioavailability enhancing property. It's a well known fact that pepper enhances bioavailability by inhibition of microsomal enzyme system but other mechanisms are also responsible to acts as a bioavailability enhancer. The brief overview of the mechanism of action of pepper as well as its applications as bioavailability enhancer is given in the present article.

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“…A recent study found no effect of St John's wort (300 mg standardized to 0.3% hypericin three times daily (14 days)) on carbamazepine pharmacokinetics [15]. Piper longum contains piperine, which has been shown in clinical trials to increase C max and AUC of phenytoin [16], propranolol, and theophylline [17].…”

Section: Discussionmentioning

confidence: 99%

Herb–drug interactions: Review and assessment of report reliability

Fugh‐Berman

Ernst

2001

Brit J Clinical Pharma

312

202

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Aims The aim of this systematic review was to assess the published clinical evidence on interactions between herbal and conventional drugs. Methods Four electronic databases were searched for case reports, case series or clinical trials of such interactions. The data were extracted and validated using a scoring system for interaction probability. Results One hundred and eight cases of suspected interactions were found. 68.5% were classi®ed as`unable to be evaluated', 13% as`well-documented' and 18.5% as possible' interactions. Warfarin was the most common drug (18 cases) and St John's wort the most common herb (54 cases) involved. Conclusion Herb±drug interactions undoubtedly do occur and may put individuals at risk. However our present knowledge is incomplete and more research is urgently needed.

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Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers

Cited by 186 publications

References 6 publications

Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4

Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4

Molecular targets of pepper as bioavailability enhancer

Herb–drug interactions: Review and assessment of report reliability

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