Human organ/tissue growth algorithms that include obese individuals and black/white population organ weight similarities from autopsy data.

Physiologically based pharmacokinetic (PBPK) models need the correct organ/tissue weights to match various total body weights in order to be applied to children and the obese individual. Baseline data from Reference Man for the growth of human organs (adrenals, brain, heart, kidneys, liver, lungs, pancreas, spleen, thymus, and thyroid) were augmented with autopsy data to extend the describing polynomials to include the morbidly obese individual (up to 250 kg). Additional literature data similarly extends the growth curves for blood volume, muscle, skin, and adipose tissue.

Windows based general PBPK/PD modeling software.

A physiologically based pharmacokinetic (PBPK) model and program (called PostNatal) was developed which focuses on postnatal growth. Algorithms defining organ/tissue growth curves from birth through adulthood for male and female humans, dogs, rats, and mice are utilized to calculate the appropriate weight and blood flow for the internal organs/tissues. This Windows based program is actually four linked PBPK models with each PBPK model acting independently or totally integrated with the others through metabolism by first order or Michaelis-Menten kinetics.

Postnatal growth considerations for PBPK modeling.

A physiologically based pharmacokinetic (PBPK) model and Windows-based program (called PostNatal) was developed that focuses on postnatal growth, from birth through adulthood, using appropriate growth curves for each species and gender. Postnatal growth algorithms relating organs/tissues weights with total body weight for male and female humans, dogs, rats, and mice are an integral part of the software and are utilized to assign the appropriate weight and blood flow for each of 22 organs/tissues for each simulation. Upper limits of body weight were chosen that reflect the available data used to define the algorithms; above these limits a set percent body weight was assigned to all organs/tissues.

Physiologically based pharmacokinetic/pharmacodynamic model for acrylamide and its metabolites in mice, rats, and humans.

A physiologically based pharmacokinetic model was developed for acrylamide (AA) and three of its metabolites: glycidamide (GA) and the glutathione conjugates of acrylamide (AA-GS) and glycidamide (GA-GS). Liver GA-DNA adducts and hemoglobin (Hb) adducts with AA and GA were included as pharmacodynamic components of the model. Serum AA and GA concentrations combined with urinary elimination levels for all four components from male and female mice and rats were simulated from iv and oral administration of 0.