Review and Evaluation of the Potential Impact of Age- and Gender-Specific Pharmacokinetic Differences on Tissue Dosimetry
| Autor: | Greg Lawrence, Tammie R. Covington, Justin G. Teeguarden, Annette M. Shipp, Ramesh Sarangapani, Tracy McDonald, Robinan Gentry, Harvey J. Clewell |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Physiologically based pharmacokinetic modelling Chemical compound Pharmacology Toxicology Models Biological Risk Assessment Xenobiotics Age and gender chemistry.chemical_compound Sex Factors Pharmacokinetics Environmental health Animals Humans Medicine Dosimetry Young adult Potential impact Dose-Response Relationship Drug business.industry Age Factors chemistry Carcinogens Female Risk assessment business |
| Zdroj: | Critical Reviews in Toxicology. 32:329-389 |
| ISSN: | 1547-6898 1040-8444 |
| DOI: | 10.1080/20024091064264 |
| Popis: | In standard risk assessment methods for carcinogenic or noncarcinogenic chemicals, quantitative methods for evaluating interindividual variability are not explicitly considered. These differences are currently considered by the use of statistical confidence limits or default uncertainty factors. This investigation consisted of multiple tasks aimed at making quantitative predictions of interindividual differences in susceptibility by using physiologically based pharmacokinetic (PBPK) models. Initially, a systematic, comprehensive review of the literature was conducted to identify any quantitative information related to gender- or age-specific physiological and biochemical factors that could influence susceptibility to chemical exposure. These data were then organized from a pharmacokinetic perspective by process and by chemical class to identify key factors likely to have a significant impact on susceptibility as it relates to internal target tissue dose. Overall, a large number of age- and gender-specific quantitative differences in pharmacokinetic parameters were identified. The majority of these differences were identified between neonates/children and adults, with fewer differences identified between young adults and the elderly. The next phase of this work consists of using PBPK models to develop examples of approaches through the development of case studies. The goal of the case studies is to continue to develop a methodology that incorporates PBPK modeling to assess the likelihood that a chemical or class of chemicals may present an age- or gender-specific risk. The case studies should also demonstrate practical methods for quantitatively incorporating information on age- and gender-specific pharmacokinetic differences in risk assessments for chemicals. |
| Databáze: | OpenAIRE |
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