title: Sensitivity analysis for physiologically based pharmacokinetic models.
abstract: The present study evaluates the sensitivity of pharmacokinetic model output to variability in the biochemical and metabolic input parameters. Pharmacokinetic models of three chemicals are chosen for analysis: styrene, methylchloroform, and methylene chloride. Results show that model sensitivities are time-, dose-, and species-dependent and that the most sensitive parameters are the maximum Michaelis-Menten metabolism rate Vmax and the blood/air and fat/air partition coefficients. For humans, the muscle/air partition coefficient is also important. Model output is insensitive to the Michaelis-Menten parameter Km (except for low doses) and to other tissue/air partition coefficients.
authors.affiliation: Computing and Telecommunications Division, Oak Ridge National Laboratory, Tennessee 37831.
authors.forename: D M
authors.initials: DM
authors.lastname: Hetrick
authors.forename: A M
authors.initials: AM
authors.lastname: Jarabek
authors.forename: C C
authors.initials: CC
authors.lastname: Travis
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D008752:Methylene Chloride / Q000737:chemistry / Q000493:pharmacokinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D010599:Pharmacokinetics; D051381:Rats; D013045:Species Specificity; D013223:Statistics as Topic; D013343:Styrenes / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014240:Trichloroethanes / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D013343:Styrenes; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D008752:Methylene Chloride