Further Investigation of Amantadine Disposition: Acetylation and Secretion

Simple item page
dc.contributor.authorFatani, Solafa
dc.contributor.examiningcommitteeHatch, Grant (Pharmacology and Therapeutics) McNicol, Archie (Dentistry)en
dc.contributor.supervisorSitar, Daniel (Pharmacology and Therapeutics)en
dc.date.accessioned2010-04-08T22:12:59Z
dc.date.available2010-04-08T22:12:59Z
dc.date.issued2010-04-08T22:12:59Z
dc.degree.disciplinePharmacology and Therapeuticsen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractAmantadine is a cationic aliphatic primary amine eliminated by the kidneys, excreted predominantly unchanged into the urine, and undergoes limited metabolism. Renal tubule secretion has an important role in its elimination. We studied two aspects of amantadine disposition, firstly acetylation, by developing a model to induce the enzyme spermidine/spermine N1-acetyltransferase (SSAT1) with N1, N11-diethylnorspermine (DENSPM) and alcohol (Alc) as representative agents reported to induce its activity, and secondly renal secretion, by studying the effect of intravenous bicarbonate infusion on its renal elimination. We drew two conclusions, firstly, longer exposure to Alc combined with DENSPM administration provided the greatest potentiation of SSAT1 enzyme activity than each agent alone, which indicates a high likelihood of synergy between Alc and DENSPM; and secondly, bicarbonate load administered to healthy male volunteers impairs amantadine renal secretion in the absence of a clinically important change in blood pH, serum creatinine concentration or urinary creatinine clearance.en
dc.description.noteFebruary 2010en
dc.format.extent1521952 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/1993/3937
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectamantadineen
dc.subjectspermidine/spermine N1-acetyltransferaseen
dc.subjectbicarbonateen
dc.subjectN1, N11-diethylnorspermineen
dc.titleFurther Investigation of Amantadine Disposition: Acetylation and Secretionen
dc.typemaster thesisen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Fatani Investigation of Amantadine Disposition.pdf
Size:
1.46 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.34 KB
Format:
Item-specific license agreed to upon submission
Description:
Download
Collections
FGS - Electronic Theses and Practica