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Clinical pharmacokinetic simulation/modeling as a tool for therapeutic drug monitoring and dose adjustment in special patient populations

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dc.contributor.advisor Ayres, James W.
dc.creator Mohamed, Osama H.
dc.date.accessioned 2012-06-08T17:04:51Z
dc.date.available 2012-06-08T17:04:51Z
dc.date.copyright 2004-08-06
dc.date.issued 2004-08-06
dc.identifier.uri http://hdl.handle.net/1957/29720
dc.description Graduation date: 2005 en_US
dc.description.abstract This dissertation describes how to apply pharmacokinetic simulations and modeling in a clinical setting to monitor and adjust drug dosing in special patient populations. Pharmacokinetic simulations were used to investigate efficacy and risk of drug toxicity of a new dosing regimen for aminoglycoside antibiotics when administered to renal failure patients. The current method of administering aminoglycosides to renal failure patients is to dose the drug during the last half hour of dialysis sessions. The new proposed method suggests dosing the drug during the first half hour of the dialysis session. Using one-compartment model infusion equations, both methods were simulated to predict drug peaks, troughs and area under the curves. These parameters were used to compare both dosing regimens to find out if the proposed dosing regimen can be suggested in a clinical setting to obtain the same efficacy and lower risk of drug toxicity. The dissertation then describes a prospective clinical study in chronic renal failure patients who received the same tobramycin dose using current and proposed dosing regimens. Results from the clinical study confirm pharmacokinetic simulations and modeling outcomes. Results suggest that both regimens have the same efficacy, but the new proposed method is expected to have lower risk of drug toxicity. The dissertation also describes a retrospective study for vancomycin dosing in renal failure patients. The objective was to confirm that pharmacokinetic modeling could be used to predict and adjust vancomycin dosing for this special population. Vancomycin trough concentrations obtained from patient medical records were compared to predictions obtained using a pharmacokinetic model. It was concluded that there was no statistically significant difference between actual and predicted vancomycin trough concentrations. These results suggest that the pharmacokinetic model can be used to predict and adjust vancomycin dosing to chronic renal failure population. The last part of this dissertation describes evaluation of insulin glargine effect on glycemic control and weight change in a diabetic population. Glycemic control and weight of patients before and after initiation of insulin glargine were evaluated retrospectively. Results showed that initiation of insulin glargine improved glycemic control while weight remained relatively stable. en_US
dc.language.iso en_US en_US
dc.subject.lcsh Hemodialysis en_US
dc.subject.lcsh Chronic renal failure -- Treatment en_US
dc.subject.lcsh Aminoglycosides -- Pharmacokinetics en_US
dc.subject.lcsh Aminoglycosides -- Administration en_US
dc.title Clinical pharmacokinetic simulation/modeling as a tool for therapeutic drug monitoring and dose adjustment in special patient populations en_US
dc.type Thesis/Dissertation en_US
dc.degree.name Doctor of Philosophy (Ph. D.) in Pharmacy en_US
dc.degree.level Doctoral en_US
dc.degree.discipline Pharmacy en_US
dc.degree.grantor Oregon State University en_US
dc.description.digitization File scanned at 300 ppi (Monochrome, 24-bit Color) using Capture Perfect 3.0.82 on a Canon DR-9080C in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR. en_US
dc.description.peerreview no en_us

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