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Title: Chiral pharmacokinetics of fluoxetine
Other Titles: Chiral pharmacokinetics of fluoexetine; pharmacogenetic aspects of its metabolism and disposition
Authors: Sghendo, Lino
Keywords: Pharmacokinetics
Issue Date: 2015
Citation: Sghendo L. (2015). Chiral pharmacokinetics of fluoxetine (Doctoral dissertation).
Abstract: BACKGROUND Fluoxetine is a selective serotonin reuptake inhibitor and has been analysed in pharmacokinetic studies mainly by chromatographic techniques. DESIGN A novel, robust and reproducible chiral gas chromatographic method for the separation and measurcmcnt of the cnantiomcrs of fluoxetine and norfluoxetine, in urine and plasma, was developed. The method was applied in cumulative urine excretion studies and oral saliva population pharmacokinetic studies. METHODS The technique involved the use of GC/MS instrumentation for the acquisition of data in the electron impact, selective-ion monitoring mode. Three male Maltese patients and two female Maltese patients (n = 5), with a mean age of 45.9±14.6 years donated a single sample of urine and oral fluid, one hour after a morning dose of racemic fluoxetine and the samples were analysed by the developed method. Algorithms were developed either mathematically or by software in order to carry out pharmacokinetic studies. RESULTS Calibration curves for enantiomers were linear with high correlation values ranging between 0.88 and 0.97. In cumulative studies, mean half-lives equalled 97.47±0.14h for (S)-fluoxetine, 97.52± 0.34h for (R)-fluoxetine, 113.61±0.19h for (S)-norfluoxetine and 113.55±0.39h for (R)norfluoxetine. In population studies, mean half-lives equalled 42.64±11.65h for (S)-fluoxetine, 47.63±2.61h for (R)-fluoxetine, 197.81±0.32h for (S)-norfluoxetine and 199.72±1.00h for (R)norfluoxetine. DISCUSSION The results showed that the methodology was robust enough for application in pharmacokinetic studies. The pharmacokinetic studies generated results that conformed to literature. CONCLUSION The studies could be applied in therapeutic drug monitoring of the enantiomers.
Description: PharmD
Appears in Collections:Dissertations - FacM&S - 2015
Dissertations - FacM&SPha - 2015

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