Scaling basic toxicokinetic parameters from rat to man.

Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinical trials of investigational new drugs. Current strategies for scaling either doses of xenobiotics or the dispositional parameters of xenobiotics from animals to man rely on models that take account principally of species differences in weight or body surface area. Interspecies scaling of dispositional parameters such as clearance or volume of distribution commonly involves the comparison of estimates of these parameters for a given xenobiotic among numerous species on the basis of weight with the resultant mathematical relationship used to predict the values of those parameters for that xenobiotic in a species weighing, on average, about 70 kg (i.e., a man). Our approach has been to ascertain whether a useful mathematical model could be developed for predicting the dispositional parameters of a xenobiotic, its half-life and volume of distribution, in humans based exclusively on estimates of those parameters in rats. Based on a data set of about 100 different xenobiotics, we found that values for half-life and volume of distribution of a xenobiotic in humans can be predicted from the estimates of those parameters in rats. ImagesFigure 1.Figure 2.

• Publication year

  1996

• Venue

  Environmental Health Perspectives

• Publication date

  1996-04-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1289/EHP.96104400PMID 8732950PMCID 1469326
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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