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Pharmacokinetics of chemopreventive compounds
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Wu, Rachel Tsai-Han. Pharmacokinetics of chemopreventive compounds. Retrieved from https://doi.org/doi:10.7282/T3P84C6T

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TitlePharmacokinetics of chemopreventive compounds
NameWu, Rachel Tsai-Han (author); Kong, Tony (internal member); Zhou, Renping (internal member); Minko, Tamara (outside member); Rutgers University; Graduate School - New Brunswick
Date Created
Other Date2008-10 (degree)
SubjectPharmaceutical Science, Antioxidants--Physiological effect, Pharmacokinetics
Extentxi, 42 p. : ill.
DescriptionCancer claims millions of lives per year. In an effort to find cures to cancer, scientists have turned to chemopreventive compounds that are ingested by humans on a daily basis. Butylated hydroxyanisole (BHA) is a synthetic phenolic antioxidant that is commonly used as a food preservative. Previous studies done on BHA have shown it to exhibit a wide range of biological activities that include protection against acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, and its potential tumor-promoting activities. Other studies have shown it to have chemopreventive effects. However, little is known about the pharmacokinetics of BHA. The first part of this thesis proposes a study to understand the pharmacokinetics of BHA better. The data showed that BHA followed linear pharmacokinetics within the tested intravenous doses of 10 and 25 mg/kg. The volume of distribution was found to be 1.8 L/kg with a plasma clearance of 60 mL/min/kg and a half-life of 0.7 hr. The bioavailability of BHA at oral doses of 25 mg/kg and 200 mg/kg was found to be 33% and 6%, respectively. The second part of this thesis investigates the effect that Nuclear E2-factor related factor 2 (Nrf2) has on the pharmacokinetics of BHA. Nrf2 belongs to the Cap'n'Collar family of basic region-leucine zipper transcription factors, has been shown to be an essential component of ARE-binding transcriptional machinery. Nrf2 is thought to facilitate the induction of many phase II detoxifying genes. The results of this study showed that Nrf2 deficient mouse had more extended and greater exposure to BHA when the compound is given orally than Nrf2 wild type mice. This suggests that Nrf2 gene may be involved in the metabolism of BHA. The third part of this thesis investigates the usage of nanoparticle drug delivery systems. Previous pharmacokinetics studies done on chemopreventive compound, Dibenzoylmethane (DBM), which is a β-diketone structural analog of curcumin, is a minor constituent of licorice, yield unfavorable results. The bioavailability of DBM when given orally was found to be only 7%. This study was proposed in an effort to increase the bioavailability of DBM. The data showed promising results. When DBM was administered orally to rats in a nanoparticle emulsion, all the pharmacokinetic parameter values increased significantly, compared to the pharmacokinetics parameter values yielded after oral administration of an equal dose in the previous delivery vehicle. The bioavailability increased from 7% to 36% at an oral dose of 250 mg/kg. Similar results were found in a test done on mice.
NoteM.S.
NoteIncludes bibliographical references (p. 41-42)
Noteby Rachel Tsai-Han Wu
Genretheses, ETD graduate
Persistent URLhttps://doi.org/doi:10.7282/T3P84C6T
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameNjNbRU
RightsThe author owns the copyright to this work.
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