Loperamide and Piperine
new to this site ....although been trolling it for a while. then I came across this thread and I had to post a study I found on Piperine (Black Pepper extract) and its effects on inhibiting PGP. The article also mentions other substances that inhibit this enzyme. thanks, here is the link and i posted the article in case it is taken down for some reason.
http://jpet.aspetjournals.org/content/302/2/645.short
Also see -->
http://www.answers.com/topic/piperine
Piperine has also been found to inhibit human CYP3A4 and P-glycoprotein, enzymes important for the metabolism and transport of xenobiotics and metabolites.[9] In animal studies, piperine also inhibited other enzymes important in drug metabolism.[10][11] By inhibiting drug metabolism, piperine may increase the bioavailability of various compounds and alter the effectiveness of some medications.[10] Notably, piperine may enhance bioavailability of curcumin by 2000% in humans.[12] The exact mechanism of piperine's bioavailability enhancing abilities is unknown.[13]
Read more:
http://www.answers.com/topic/piperine#ixzz1gC0l77mG
Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4
Rajinder K. Bhardwaj1,2,
Hartmut Glaeser1,
Laurent Becquemont1,
Ulrich Klotz1,
Suresh K. Gupta2 and
Martin F. Fromm1
+ Author Affiliations
1Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (R.K.B., H.G., L.B., U.K., M.F.F.); and 2Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India (R.K.B., S.K.G.)
Prof. Ulrich Klotz, Ph.D., Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Auerbachstrasse 112, D-70376 Stuttgart, Germany. E-mail:
[email protected]
Abstract
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 drug-metabolizing 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 P-glycoprotein 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 IC50 values of 15.5 and 74.1 μM, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with Ki values of 36 ± 8 (liver 1)/49 ± 6 (liver 2) and 44 ± 10 (liver 1)/77 ± 10 μM (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.
Footnotes
This work was supported by the Deutscher Akademischer Austauschdienst (to R.B.; Bonn, Germany), Council of Scientific and Industrial Research (New Delhi, India), the Association Francaise pour la Recherche Therapeutique (
www.afrt.org, to L.B., France), the Deutsche Forschungsgemeinschaft (Fr1298/2-1; Bonn, Germany), and the Robert Bosch Foundation (Stuttgart, Germany).
DOI: 10.1124/jpet.102.034728
Abbreviations:
HIV
human immunodeficiency virus
TEER
transepithelial resistance
Received February 12, 2002.
Accepted March 26, 2002.
The American Society for Pharmacology and Experimental Therapeutics
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