Physiologically based pharmacokinetic modeling for prediction of pharmacokinetic parameters of capreomycin
Date
2010
Authors
Metzler, Catherine, author
Reisfeld, Brad, advisor
DeGroote, Mary Ann, committee member
Prasad, Ashok, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Tuberculosis (TB) is a global public health epidemic that is increasingly dangerous and difficult to treat due in large part to drug-resistant strains. New pharmaceutical options must be considered, including capreomycin, an antibiotic discovered in the 1950s but rarely used. Due to more effective, less renal-toxic drugs, capreomycin has not been used as a primary antibiotic in tuberculosis. However, capreomycin has reemerged due to the increase in multi drug resistant TB (MDRTB). Because of its importance in treating drug-resistant strains of TB, improving the understanding of the effective dosages and resulting side effects of capreomycin is necessary. By using a validated model, drugs of interest like capreomycin could be rapidly evaluated for initial recommendations thus reducing drug development time. Using physiologically-based pharmacokinetic (PBPK) models as predictors would be economically and time efficient. In this study, a PBPK model in combination with experimental concentration profiles in mice was used to predict capreomycin pharmacokinetic parameters. Through scale-up of the model to human physiology, and implementation of the hypothesized pharmacokinetic parameters, human organ concentration profiles were predicted and compared to literature data to assess the model capabilities. The model and parameters are anticipated to be useful in predicting the disposition of capreomycin in the mouse via various dosing regimens. Although the model is useful in making pharmaeokinetic predictions in the mouse, the parameter values will need to be adjusted appropriately to be useful for estimating ADME in humans.
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Print version deaccessioned 2022.
Print version deaccessioned 2022.
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Subject
Pharmacokinetics
Aminoglycosides