ReviewEnvironmental health perspectives1997
Estimating xenobiotic half-lives in humans from rat data: influence of log P.
Review in Environmental health perspectives, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Exposure Prioritization (Toxics · 2022Article
- Quantum Chemical Lipophilicities of Antimalarial Drugs in Relation to Terminal Half-Life.ACS omega · 2020Article
- Evaluating the Impact of Uncertainties in Clearance and Exposure When Prioritizing Chemicals Screened in High-Throughput Assays.Environmental science & technology · 2016Article
- Estimating Margin of Exposure to Thyroid Peroxidase Inhibitors Using High-Throughput in vitro Data, High-Throughput Exposure Modeling, and Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.Pharmacological reports : PR · 2015Article
- The fate of inhaled (14)C-labeled PCB11 and its metabolites in vivo.Environment international · 2014Article
- Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies.Drug design, development and therapy · 2014Article
- Toxicogenomic evaluation of long-term hepatic effects of TCDD in immature, ovariectomized C57BL/6 mice.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Effects of developmental exposure to polychlorinated biphenyls and/or polybrominated diphenyl ethers on cochlear function.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- Towards a better prediction of peak concentration, volume of distribution and half-life after oral drug administration in man, using allometry.Clinical pharmacokinetics · 2011Article
- Structural modulation of oxidative metabolism in design of improved benzothiophene selective estrogen receptor modulators.Drug metabolism and disposition: the biological fate of chemicals · 2009Article
- Quantitative structure-activity relationships (QSARs) within the cytochrome P450 system: QSARs describing substrate binding, inhibition and induction of P450s.Inflammopharmacology · 2003Article
- Cytochromes P450 and species differences in xenobiotic metabolism and activation of carcinogen.Environmental health perspectives · 1998Review
- Allometric scaling of pharmacokinetic parameters in drug discovery: can human CL, Vss and t1/2 be predicted from in-vivo rat data?European journal of drug metabolism and pharmacokineticsArticle
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nature of empirical allometric expressions relating dispositional and kinetic parameters for a given xenobiotic across multiple mammalian species is well known. It has also been demonstrated that a simple allometric relationship may be used to predict kinetic parameters for humans based merely on data for multiple xenobiotics from rats. We decided to explore reasons for the variance in the data arising from the latter method. We were particularly interested in learning whether any physicochemical characteristics of xenobiotics might account for outlying data points (i.e., poor prediction of human half-life from rat half-life). We have explored the influence of lipid solubility as reflected by a xenobiotic's log P value because adipose tissue comprises a significantly larger percentage of total body weight in humans than in rats. We used half-life data from the literature for 127 xenobiotics. A data subset of 102 xenobiotics for which we were able to find estimates of log P values, including several with extremely large log P values, was also analyzed. First and second order models, including and excluding log P, were compared. The simplest of these models can be recast as the familiar allometric relationship having the form Y = a(Xb). The remaining models can be seen as extensions of this relationship. Our results suggest that incorporation of log P into the prediction of xenobiotic half-life in humans from rat half-life data is important only for xenobiotics with extremely large log P values such as dioxins and polychlorinated biphenyls. Moreover, a second order model in logarithm of rat half-life accommodates all data points very well, without specifically accounting for log P values.
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