A Physiologically Based Pharmacokinetic Model for Capreomycin
| Autor: | Michael A. Lyons, Elizabeth J. Brooks, C. P. Metzler, Mary Ann DeGroote, Arthur N. Mayeno, Brad Reisfeld |
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| Rok vydání: | 2012 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Capreomycin Computer science Antitubercular Agents Computational biology Pharmacology Kidney Bayesian inference Models Biological Mice Bayes' theorem Pharmacokinetics medicine Animals Humans Computer Simulation Tissue Distribution Pharmacology (medical) ADME Computational model Kidney metabolism Bayes Theorem Biological Transport Mice Inbred C57BL Infectious Diseases Female Monte Carlo Method medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 56:926-934 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.05180-11 |
| Popis: | The emergence of multidrug-resistant tuberculosis (MDR-TB) has led to a renewed interest in the use of second-line antibiotic agents. Unfortunately, there are currently dearths of information, data, and computational models that can be used to help design rational regimens for administration of these drugs. To help fill this knowledge gap, an exploratory physiologically based pharmacokinetic (PBPK) model, supported by targeted experimental data, was developed to predict the absorption, distribution, metabolism, and excretion (ADME) of the second-line agent capreomycin, a cyclic peptide antibiotic often grouped with the aminoglycoside antibiotics. To account for interindividual variability, Bayesian inference and Monte Carlo methods were used for model calibration, validation, and testing. Along with the predictive PBPK model, the first for an antituberculosis agent, this study provides estimates of various key pharmacokinetic parameter distributions and supports a hypothesized mechanism for capreomycin transport into the kidney. |
| Databáze: | OpenAIRE |
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