Data for Physiologically Based Pharmacokinetic Modeling in Neonatal Animals: Physiological...
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Journal of Children's Health: Vol. 2, Nos. 3-4, pp. 363-411 (2004) Copyright© 2004 ASP ISSN: 0888-0018 print I 1521-0669 online DOl: 10.1080/15417060490970430 Data for Physiologically Based Pharmacokinetic Modeling in Neonatal Animals: Physiological Parameters in Mice and Sprague-Dawley Rats P. Robinan Gentry, 1 Lynne T. Haber, 2 Tracy B. McDonald, 1 Qiyu Zhao, 2 Tammie Covington, 1 Patricia Nance, 2 Harvey J. Clewell III, 3 John C. Lipscomb, 4 and Hugh A. Barton 5 1 ENVIRON International Corporation, Ruston, LA; 2 Toxicalogy Excellence for Risk Assessment, Cincinnati, OH; 3 CIIT Centers for Health Research, Research Triangle Park, NC; 4 U.S. EPA, NCEA, Cincinnati, OH; 5 U.S. EPA, NHEERL, Research Triangle Park, NC Corresponding author: P. Robinan Gentry, ENVIRON International Corporation, 602 East Georgia Avenue, Ruston, LA 71270. Telephone: 318-255-2277; Fax: 318-255-2040; E-mail: [email protected] 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 eval- uated. A useful way of addressing this issue is to use physiologically based phanna- cokinetic (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 clear- ance, 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 1 4 . The database is available on request from the corresponding author. Key Words: neonate, physiological parameters, child, allometry 363
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Transcript of Data for Physiologically Based Pharmacokinetic Modeling in Neonatal Animals: Physiological...
Journal of Children's Health: Vol. 2, Nos. 3-4, pp. 363-411 (2004) Copyright© 2004 ASP ISSN: 0888-0018 print I 1521-0669 online DOl: 10.1080/15417060490970430
Data for Physiologically Based Pharmacokinetic Modeling in Neonatal Animals: Physiological Parameters in Mice and Sprague-Dawley Rats
P. Robinan Gentry, 1 Lynne T. Haber, 2 Tracy B. McDonald, 1 Qiyu Zhao, 2
Tammie Covington, 1 Patricia Nance,2 Harvey J. Clewell III,3 John C. Lipscomb,4
and Hugh A. Barton5
1 ENVIRON International Corporation, Ruston, LA; 2 Toxicalogy Excellence for Risk Assessment, Cincinnati, OH; 3 CIIT Centers for Health Research, Research Triangle Park, NC; 4 U.S. EPA, NCEA, Cincinnati, OH; 5 U.S. EPA, NHEERL, Research Triangle Park, NC
Corresponding author: P. Robinan Gentry, ENVIRON International Corporation, 602 East Georgia Avenue, Ruston, LA 71270. Telephone: 318-255-2277; Fax: 318-255-2040; E-mail: [email protected]
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 phannacokinetic (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 bw314. The database is available on request from the corresponding author.
Key Words: neonate, physiological parameters, child, allometry
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