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Pharmacokinetic and pharmacodynamic investigations of select natural products and nutraceuticals for human and veterinary health

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dc.contributor.supervisor Davies, Neal (Pharmacy) en_US
dc.contributor.author Martinez, Stephanie
dc.date.accessioned 2016-03-22T15:32:51Z
dc.date.available 2016-03-22T15:32:51Z
dc.date.issued 2013-01 en_US
dc.date.issued 2013 en_US
dc.date.issued 2014-08 en_US
dc.date.issued 2015-05 en_US
dc.date.issued 2015-07 en_US
dc.date.issued 2015-09 en_US
dc.date.issued 2013 en_US
dc.date.issued 2013 en_US
dc.date.issued 2013 en_US
dc.date.issued 2013 en_US
dc.identifier.citation Martinez SE, Sayre CL, Davies NM. Analysis of 3-methoxypterostilbene in biological fluids by high-performance liquid chromatography: application to pre-clinical pharmacokinetics. Biomed Chromatogr. 2013 Jan;27(1):67-72. en_US
dc.identifier.citation Martinez SE, Sayre CL, Davies NM. Pharmacometrics of 3-methoxypterostilbeneL a component of traditional Chinese medicinal plants. Evid Based Complement Alternat Med. 2013;2013:261468. en_US
dc.identifier.citation Martinez SE, Lakowski TM, Davies NM. Enantiospecific analysis of 8-prenylnaringenin in biological fluids by liquid-chromatography-electrospray ionization mass spectrometry: application to preclinical pharmacokinetic investigations. Chirality. 2014 Aug;26(8):419-26. en_US
dc.identifier.citation Martinez SE, Davies NM. Stereospecific quantitation of 6-prenylnaringenin in commercially available H. lupulus-containing natural health products and dietary supplements. Res Pharm Sci .2015 May-Jun;10(3):182-91. en_US
dc.identifier.citation Martinez SE, Chen Y, Ho EA, Martinez SA, Davies NM. Pharmacological effects of a C-phycocyanin-based multicomponent nutraceutical in an in-vitro canine chondrocyte model of osteoarthritis. Can J Vet Res. 2015 Jul;79(3):241-9. en_US
dc.identifier.citation Martinez SE, Davies NM. Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat. Mol Nutr Food Res. 2015 Sep;59(9):1674-89. en_US
dc.identifier.citation Martinez SE, Davies NM, Reynolds JK. Toxicology and Safety of Flavonoids. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013. en_US
dc.identifier.citation Takemoto JK, Martinez SE, Davies NM. Analysis of Flavonoids through Chromatography. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013. en_US
dc.identifier.citation Yáñez JA, Sayre CL, Martinez SE, Davies NM. Chiral Methods of Flavonoid Analysis. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013. en_US
dc.identifier.citation Yáñez JA, Remsberg CM, Takemoto JK, Vega-Villa KR, Andrews PK, Sayre CL, Martinez SE, Davies NM. Polyphenols and Flavonoids: An Overview. In Davies NM & Yáñez JA (Eds.), Flavonoid Pharmacokinetics: Methods of Analysis, Pre-Clinical and Clinical Pharmacokinetics, Safety and Toxicology. New York: John Wiley and Sons, Inc., 2013. en_US
dc.identifier.uri http://hdl.handle.net/1993/31166
dc.description.abstract Natural products are teeming with potential therapeutic agents. One group of compounds, polyphenols, from plants, exhibit anti-cancer, anti-inflammatory and anti-oxidant activities. Four polyphenolic compounds and their enantiomers were investigated in this thesis; the stilbene, 3-methoxypterostilbene, a structural analog of resveratrol, and the chiral prenylflavonoids from hops (Humulus lupulus L.); 8-prenylnaringenin, 6-prenylnaringenin and isoxanthohumol. A high performance liquid chromatography method for 3-methoxypterostilbene and enantiospecific liquid chromatography-mass spectrometry assays for the three prenylflavonoids were developed and validated. The methods allowed for quantification of these four polyphenols in biological samples and plant-based materials. Content analysis studies of 3-methoxypterostilbene and the three prenylflavonoids in traditional Chinese medicinal plants and hops-containing nutraceuticals were carried out, respectively. The pharmacokinetics of these four compounds were delineated through intravenous and oral administration in rats. 3-Methoxypterostilbene demonstrated greater bioavailability in rats than reported values for resveratrol. Enantiomeric differences in disposition parameters were observed for the three prenylflavonoids along with differences between compounds despite only small structural differences. The in vitro pharmacodynamics of these four compounds were elucidated including anti-oxidant, anti-inflammatory, anti-diabetic and cytochrome P450 modulation activities. All four compounds demonstrated a range of bioactivities related to chronic diseases and potential drug-botanical interactions. Further studies of polyphenols, especially clinical studies, are needed along with enantiospecific study when applicable to continue delineating the importance of bioactivity, pharmacokinetics and safety. Natural products are further developed into nutraceuticals and sold over-the-counter for both human and veterinary use but are not currently required to demonstrate efficacy prior to marketing. In the final section of this thesis, Phycox®, a multi-component veterinary nutraceutical for joint health was investigated for pharmacological activity in an in vitro model of canine osteoarthritis along with select constituents. A pilot single-dose pharmacokinetic study in dogs was also undertaken. Two liquid chromatography tandem mass spectrometry methods were developed and validated to detect constituents in serum. In vitro study results indicated that Phycox® was able to reduce inflammatory mediators similar to the NSAID, carprofen, and acute pharmacokinetic results revealed that detectable concentrations of glucosamine were evident in serum. It is suggested that further clinical studies of Phycox® are warranted to optimize its usage. en_US
dc.publisher John Wiley & Sons, Ltd. en_US
dc.publisher Hindawi Publishing Corporation en_US
dc.publisher Wiled Periodicals, Inc. en_US
dc.publisher Medknow Publications en_US
dc.publisher Canadian Veterinary Medical Association en_US
dc.publisher WILEY-VCH Verlag CmbH & Co. en_US
dc.publisher John Wiley and Sons, Inc. en_US
dc.publisher John Wiley and Sons, Inc. en_US
dc.publisher John Wiley and Sons, Inc. en_US
dc.publisher John Wiley and Sons, Inc. en_US
dc.subject Pharmacokinetics en_US
dc.subject Pharmacodynamics en_US
dc.subject Flavonoids en_US
dc.subject Natural products en_US
dc.subject Veterinary nutraceutical en_US
dc.subject Stilbenes en_US
dc.subject Methods of analysis en_US
dc.subject Chiral flavonoids en_US
dc.subject Humulus lupulus L. en_US
dc.subject Content analysis en_US
dc.title Pharmacokinetic and pharmacodynamic investigations of select natural products and nutraceuticals for human and veterinary health en_US
dc.degree.discipline Pharmacy en_US
dc.contributor.examiningcommittee Burczysnki, Frank (Pharmacy) Gong, Yuewen (Pharmacy) Beta, Trust (Food Science) Lefebvre, Jean (Laval University) en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US
dc.description.note May 2016 en_US


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