This thesis examines the mechanisms by which natural health products (NHP)s may affect drug disposition pathways. Adverse reactions from concomitant NHP-drug use may result from competing interactions at the level of the metabolic enzyme cytochrome P450 3A4 (CYP3A4) or the xenobiotic efflux pump P-glycoprotein (P-gp). NHPs and drugs relevant to HIV were assessed for their ability to affect these drug disposition pathways.
NHP extracts were examined for their ability to inhibit CYP3A4 and stimulate P-gP ATPase. Goldenseal (GS) NHPs were the most inhibitory of CYP3A4; GS and milk thistle (MT) teas stimulated P-gp ATPase more than the positive control verapamil.
GS and MT extracts, related phytochemicals, and several HIV drugs were screened for their ability to modulate CYP3A4 and P-gp ( ABCB1 gene product) expression in caco2 cell monolayers. ABCB1 expression did not change from control levels; CYP3A4 expression was more responsive, and thus a better marker for cellular response.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/26361 |
| Date | January 2003 |
| Creators | Budzinski, Jason William |
| Contributors | Arnason, J. T., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 78 p. |
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