Biomedical subjects

D M Hetrick

Publications and source records attributed to D M Hetrick.

4 recordsLinked to original sources

PubMed1991

Sensitivity analysis for physiologically based pharmacokinetic models.

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.

Administration, Inhalation↗

PubMed1988

Pharmacokinetics of tetrachloroethylene.

A physiological pharmacokinetic model is developed to describe the pharmacokinetics of tetrachloroethylene (PCE) in mice, rats, and humans. The body is divided into four tissue compartments (vessel-rich, muscle, slowly perfused fat, and liver) connected by the arterial and venous blood flow pathways. The physiological parameters of the model are blood flow rates, cardiac output, tissue volumes, ventilation rate, and tissue/air and blood/air partition coefficients. Metabolism is assumed to occur only in the liver compartment and is described by a combination of a linear metabolic component and a Michaelis-Menten component. The metabolic parameters for PCE were determined by fitting model predictions to species-specific empirical data. Comparison of model results with independent empirical data on inhalation and gavage exposures in mice, rats, and humans demonstrates that the physiological pharmacokinetic model can be used to determine the time course of PCE in these species. We show that human metabolic parameters can be predicted by scaling rat metabolic parameters as a function of body weight, whereas scaling of the metabolic parameters of mice overestimates human metabolism.

Animals↗

PubMed1984

Metabolism of organically bound tritium in man.

The classic methodology for estimating dose to man from environmental tritium assumes that all tritium, whether organically bound or free, enters directly into man's free body water compartment and is uniformly distributed as tritiated water. This methodology ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. A four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment is proposed. The utility of this model lies in the ability to input organically bound tritium directly into organic compartments representing tissue solids. The model will be used to illustrate the potential importance of organically bound tritium to cumulative dose estimates. It is found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7-4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet.

Animals↗

PubMed1984

Validation of a metabolic model for tritium.

The purpose of this paper is to validate a metabolic model describing the kinetics of tritium in man. The validation is based on measurements of background levels of loose and bound tritium in Italian subjects and their diets. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement.

Diet↗