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Clinical pharmacokinetic simulation/modeling as a tool for therapeutic drug monitoring and dose adjustment in special patient populationsMohamed, Osama H. 06 August 2004 (has links)
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. / Graduation date: 2005
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