title: Database for physiologically based pharmacokinetic (PBPK) modeling: physiological data for healthy and health-impaired elderly.
abstract: Physiologically based pharmacokinetic (PBPK) models have increasingly been employed in chemical health risk assessments. By incorporating individual variability conferred by genetic polymorphisms, health conditions, and physiological changes during development and aging, PBPK models are ideal for predicting chemical disposition in various subpopulations of interest. In order to improve the parameterization of PBPK models for healthy and health-impaired elderly (herein defined as those aged 65 yr and older), physiological parameter values were obtained from the peer-reviewed literature, evaluated, and entered into a Microsoft ACCESS database. Database records include values for key age-specific model inputs such as ventilation rates, organ volumes and blood flows, glomerular filtration rates, and other clearance-related processes. In total, 528 publications were screened for relevant data, resulting in the inclusion of 155 publications comprising 1051 data records for healthy elderly adults and 115 data records for elderly with conditions such as diabetes, chronic obstructive pulmonary disease (COPD), obesity, heart disease, and renal disease. There are no consistent trends across parameters or their associated variance with age; the gross variance in body weight decreased with advancing age, whereas there was no change in variance for brain weight. The database contains some information to inform ethnic and gender differences in parameters; however, the majority of the published data pertain to Asian (mostly Japanese) and Caucasian males. As expected, the number of records tends to decrease with advancing age. In addition to a general lack of data for parameters in the elderly with various health conditions, there is also a dearth of information on blood and tissue composition in all elderly groups. Importantly, there are relatively few records for alveolar ventilation rate; therefore, the relationship between this parameter and cardiac output (usually assumed to be 1:1) in the elderly is not well informed by the database. Despite these limitations, the database represents a potentially useful resource for parameterizing PBPK models for the elderly to facilitate the prediction of dose metrics in older populations for application in risk assessment.
authors.affiliation: National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Washington, DC 20460, USA. Thompson.Chad@epa.gov
authors.forename: Chad M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Douglas O
authors.initials: DO
authors.lastname: Johns
authors.forename: Babasaheb
authors.initials: B
authors.lastname: Sonawane
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Barton
authors.forename: Dale
authors.initials: D
authors.lastname: Hattis
authors.forename: Robert
authors.initials: R
authors.lastname: Tardif
authors.forename: Kannan
authors.initials: K
authors.lastname: Krishnan
mesh_terms: D000368:Aged; D016208:Databases, Factual; D006262:Health; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D010829:Physiological Phenomena; D012016:Reference Values