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The direct and indirect effects of h...

Komoroski, Bernard J., Jr.

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The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters./
Author:	Komoroski, Bernard J., Jr.
Description:	212 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-09, Section: B, page: 4825.
Contained By:	Dissertation Abstracts International66-09B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3188964
ISBN:	0542311445

The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters.
Komoroski, Bernard J., Jr.

The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters. - 212 p.

Source: Dissertation Abstracts International, Volume: 66-09, Section: B, page: 4825.

Thesis (Ph.D.)--University of Pittsburgh, 2005.

The increase in the use of herbal products, particularly in patients taking conventional medicine, has increased the likelihood of drug-herb interactions. Herbal products sold to the public are often not a single chemical compound, but rather a complex mixture of hundreds of different constituents. Human microsomal systems have been employed as a cost and time efficient approach to prospectively evaluate individual constituents for the potential for interactions with drug metabolizing enzymes. In fact, it has been shown that certain herbal constituents are capable of direct inhibition of drug metabolizing enzymes in this system. However, extrapolation of the drug interaction potential to cellular systems or whole organisms is often difficult because the preparation of microsomes necessitates the destruction of the integrity of the living cell and the physiologically relevant processes within. The primary goal of this dissertation research was to investigate the effect of herbal products on human hepatic drug metabolizing enzymes and transporters using primary cultures of human hepatocytes.

ISBN: 0542311445Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters.
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100 1 $a Komoroski, Bernard J., Jr. $3 1905147
245 1 4 $a The direct and indirect effects of herbal products on common drug metabolizing enzymes and drug transporters.
300 $a 212 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-09, Section: B, page: 4825.
500 $a Major Adviser: Raman Venkataramanan.
502 $a Thesis (Ph.D.)--University of Pittsburgh, 2005.
520 $a The increase in the use of herbal products, particularly in patients taking conventional medicine, has increased the likelihood of drug-herb interactions. Herbal products sold to the public are often not a single chemical compound, but rather a complex mixture of hundreds of different constituents. Human microsomal systems have been employed as a cost and time efficient approach to prospectively evaluate individual constituents for the potential for interactions with drug metabolizing enzymes. In fact, it has been shown that certain herbal constituents are capable of direct inhibition of drug metabolizing enzymes in this system. However, extrapolation of the drug interaction potential to cellular systems or whole organisms is often difficult because the preparation of microsomes necessitates the destruction of the integrity of the living cell and the physiologically relevant processes within. The primary goal of this dissertation research was to investigate the effect of herbal products on human hepatic drug metabolizing enzymes and transporters using primary cultures of human hepatocytes.
520 $a Cultured hepatocytes were exposed to the various herbal constituents acutely, to evaluate the direct effect on enzyme activity, or chronically, to evaluate the indirect effect on enzyme expression and subsequent activity. Additionally, in order to assess to scalability of our in vitro UGT1A results to humans, healthy human subjects were administered acetaminophen, a general UGT1A probe, before and after a 7-day course of milk thistle.
520 $a These data demonstrate that herbal constituents can directly inhibit enzyme activity but also influence activity by indirectly modulating gene expression. In the case of St. John's wort, human hepatocytes showed that while constituents were capable of enzyme induction, inhibition also occurred. However, in vivo, it is the former that predominates over the latter. Furthermore, our predictions of interactions in vivo for St. John's wort have been validated through a number of clinical studies. The case of milk thistle, however, proved more complex. While our in vitro data showed the possibility of drug interactions with several drug metabolizing enzymes, little effect was found in vivo. The latter demonstrates the value of consideration of the entire pharmacologic profile of an herb before conclusions about clinical relevance are made.
590 $a School code: 0178.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Health Sciences, Pharmacology. $3 1017717
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773 0 $t Dissertation Abstracts International $g 66-09B.
790 1 0 $a Venkataramanan, Raman, $e advisor
790 $a 0178
791 $a Ph.D.
792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3188964