Data for Physiologically Based Pharmacokinetic Modeling in Neonatal Animals: Physiological Parameters in Mice and Sprague-Dawley Rats

ABSTRACT

Recent scientific and policy initiatives have resulted in increased interest in risk to fetuses, infants, and children and consideration of how such risks should be evaluated. A useful way of addressing this issue is to use physiologically based pharmacokinetic (PBPK) models to compare the tissue dose that children and adults receive for a given amount of a chemical ingested or inhaled. The response in children and adults for a given tissue dose can also be compared. To aid in the development of age-specific PBPK models for experimental animals, we have collected information on physiological parameters in neonates and young animals, through 60 days of age. Our effort focused on generic physiological values, such as tissue weight (termed tissue volume in the context of PBPK modeling), intake (alveolar ventilation, food intake, water intake), and flows (blood flows to tissues, bile flow, creatinine clearance, and glomerular filtration rate). To date, parameters for Sprague-Dawley rats and mice of multiple strains have been collected and evaluated for data gaps and patterns. Using this database, we found that food intake in neonates does scale with approximately bw^3/4. The database is available on request from the corresponding author.

Keywords:

• neonate
• physiological parameters
• child
• allometry

Notes

^aData consist of values from 16 litters culled to 4 neonates.

^bData consist of values from 18 litters culled to 9 neonates.

^cData consist of values from 18 litters culled to 18 neonates.

^d p < 0.001 (t-test compared to the control litter group).

^e p < 0.01 (t-test compared to the control litter group).

^f p < 0.05 (t-test compared to the control litter group).

^aMale/female means that combined data were provided for both sexes pooled; sex-specific data were not provided in the relevant references.

^aAll data are for Sprague-Dawley rats, except the data from Delp et al. (1998), which are from F344 rats.

^bDefined for this study as muscle, skeletal bones, skin, and fur.

^cListed as skeletal muscle.

^aAll data are from Sprague-Dawley rats, except for the data from Delp et al. (1998), which are from F344 rats.