Estimating metabolic rate for butadiene at steady state using a Bayesian physiologically-based pharmacokinetic model

• Published in: Environmental and ecological statistics Vol. 18; no. 1; pp. 131 - 146
• Main Authors: Ngo, Long, Ryan, Louise M, Mezzetti, Maura, Bois, Frédéric Y, Smith, Thomas J
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2011; Springer Nature B.V; Springer Verlag (Germany)
• Subjects: Age; Bayesian analysis; Biomedical and Life Sciences; breathing; Cancer; Carcinogens; Chemistry and Earth Sciences; Computer Science; Computer simulation; Differential equations; Ecology; Environmental Sciences; Estimates; Estimating techniques; females; Gender; gender differences; Health Sciences; Hispanic people; Hispanics; Human body; Inhalation; Intervals; Life Sciences; Males; Markov analysis; Markov chain; Markov chains; Math. Appl. in Environmental Science; Mathematical models; Medicine; Metabolism; Metabolites; Monkeys & apes; Monte Carlo methods; Monte Carlo simulation; Occupational safety; Pharmacokinetics; Physics; Public health; Race; Statistics for Engineering; Statistics for Life Sciences; Steady state; Studies; Theoretical Ecology/Statistics; Toxicology; Tumors; volunteers; Bayesian hierarchical model; Compartmental model; Differential equation; Random effects; Markov Chain Monte Carlo; Metabolic rate constant; Steady state; Nonlinear model
• ISSN: 1352-8505; 1573-3009
• DOI: 10.1007/s10651-009-0124-1

In a study of 133 volunteer subjects, demographic, physiologic and pharmacokinetic data through exposure to 1,3-Butadiene (BD) were collected in order to estimate the percentage of BD concentration metabolized at steady state, and to determine whether this percentage varies across gender, racial, and age groups. During the 20 min of continuous exposure to 2 parts per million (ppm) of BD, five measurements of exhaled concentration were made on each subject. In the following 40 min washout period, another five measurements were collected. A Bayesian hierarchical compartmental physiologically-based pharmacokinetic model (PKPB) was used. Using prior information on the model parameters, Markov Chain Monte Carlo (MCMC) simulation was conducted to obtain posterior distributions. The overall estimate of the mean percent of BD metabolized at steady state was 12.7% (95% credible interval: 7.7-17.8%). There was no significant difference in gender with males having a mean of 13.5%, and females 12.3%. Among the racial groups, Hispanic (13.9%), White (13.0%), Asian (12.1%), and Black (10.9%), the significant difference came from the difference between Black and Hispanic with a 95% credible interval from −5.63 to −0.30%. Those older than 30 years had a mean of 12.2% versus 12.9% for the younger group; although this was not a statistically significant difference. Given a constant inhalation input of 2 ppm, at steady state, the overall mean exhaled concentration was estimated to be 1.75ppm (95% credible interval: 1.64-1.84). An equivalent parameter, first-order metabolic rate constant, was also estimated and found to be consistent with the percent of BD metabolized at steady state across gender, race, and age strata.