Contribution of selected flavonoid enantiomers implicated in chronic disease prevention to differential pharmacokinetic and pharmacodynamic behaviour
| dc.contributor.author | Sayre, Casey L. | |
| dc.contributor.examiningcommittee | Sitar, Dan (Pharmacology & Therapeutics) Ariano, Rob (Pharmacy) Alessi-Severini, Silvia (Pharmacy) Loebenberg, Raimar (University of Alberta) | en_US |
| dc.contributor.supervisor | Davies, Neal (Pharmacy) | en_US |
| dc.date.accessioned | 2014-12-03T15:35:54Z | |
| dc.date.available | 2014-12-03T15:35:54Z | |
| 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.degree.discipline | Pharmacy | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Decreases in risk of chronic disease associated with diets high in fruits and vegetables have been observed. Difficulty in determining the active ingredients responsible for the beneficial effects of dietary plant intake comes in part from the lack of pre-clinical pharmaceutical characterization of compounds thought to play a role. Flavonoids are a class of low molecular weight secondary metabolites present in plants. Pinocembrin, pinostrobin, and liquiritigenin are three chiral flavonoid implicated in the chronic disease prevention seen in high plant diets. To further the pre-clinical development of novel compounds for the potential prevention of chronic disease, stereospecific analytical methods of detection and quantification were developed for pinocembrin, pinostrobin, and liquiritigenin in biological matrices. These methods were used to elucidate the enantiospecific pharmacokinetics of all three compounds in the rat. Additionally, pinocembrin, pinostrobin, and liquiritigenin enantiomers were quantified in multiple marketed natural health products and dietary supplements. Finally, the compounds were screened for activity in several in vitro pharmacodynamic assays with roles in chronic disease pathology to assess for potential stereopecific pharmacologic behaviour. The methods were successfully used to determine the stereospecific pharmacokinetics, pharmacodynamics, and content analysis of selected marketed products. Stereopecific differences were observed in several instances. Further stereospecific studies are needed, especially in the field of toxicokinetics. | en_US |
| dc.description.note | February 2015 | en_US |
| dc.identifier.citation | Sayre CL, Davies NM. Quantification of three chiral flavonoids with reported bioactivity in selected licensed Canadian natural health products and US marketed dietary supplements. J Pharm Pharm Sci. 2013;16(2):272-8. | en_US |
| dc.identifier.citation | Sayre CL, Takemoto JK, Martinez SE, Davies NM. Chiral analytical method development and application to pre-clinical pharmacokinetics of pinocembrin. Biomed Chromatogr. 2013 Jun;27(6):681-4. | en_US |
| dc.identifier.citation | Sayre CL, Zhang Y, Martinez SE, Takemoto JK, Davies NM. Stereospecific analytical method development and preliminary in vivo pharmacokinetic characterization of pinostrobin in the rat. Biomed Chromatogr. 2013 May;27(5):548-50. | en_US |
| dc.identifier.citation | Sayre CL, Hopkins M, Takemoto JK, Davies NM. Chiral analytical method development of liquiritigenin with application to a pharmacokinetic study. Biomed Chromatogr. 2013 Mar;27(3):404-6. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/30075 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Canadian Society for Pharmaceutical Sciences | en_US |
| dc.publisher | John Wiley and Sons | en_US |
| dc.publisher | John Wiley and Sons | en_US |
| dc.publisher | John Wiley and Sons | en_US |
| dc.rights | open access | en_US |
| dc.subject | Pharmacokinetics | en_US |
| dc.subject | Flavonoid | en_US |
| dc.title | Contribution of selected flavonoid enantiomers implicated in chronic disease prevention to differential pharmacokinetic and pharmacodynamic behaviour | en_US |
| dc.type | doctoral thesis | en_US |