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Enhancing the Modeling of PFOA Pharmacokinetics with Bayesian Analysis
Citation:
WAMBAUGH, J. F., H. A. BARTON, AND R. W. SETZER. Enhancing the Modeling of PFOA Pharmacokinetics with Bayesian Analysis. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
Performed a Bayesian analysis using Markov Chain Monte Carlo. Since PFOA excretion is known to be sexually dimorphic in rats, we analyzed the male and female data separately. The distributions of integrated plasma concentration (AUC) varied significantly because the clearance is much higher in females (35.6±9.2 mL/kg/h) than in males (0.81±0.24 mL/kg/h).
Description:
The detail sufficient to describe the pharmacokinetics (PK) for perfluorooctanoic acid (PFOA) and the methods necessary to combine information from multiple data sets are both subjects of ongoing investigation. Bayesian analysis provides tools to accommodate these goals. We examined the results of a series of experiments [Kemper, 2003] that observed the concentration of PFOA in male and female adult rats. For some subjects plasma concentration was observed over time, while for others feces and urine were collected. Assuming that the PK parameters for each individual were drawn from the same, biologically-varying population, we jointly analyzed both types of data. This hierarchical approach allowed us to estimate the contributions of uncertainty due to measurement error and actual biological variability.