Title : Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: a case study with toluene.

Pub. Date : 2006 Jul 1

PMID : 16464483






3 Functional Relationships(s)
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1 The objective of the present study was to evaluate the magnitude of interindividual variability in the internal dose of toluene in children of various age groups, on the basis of subject-specific hepatic CYP2E1 content and physiology. Toluene cytochrome P450 family 2 subfamily E member 1 Homo sapiens
2 The adult toluene PBPK model, with enzyme content-normalized CL(int), facilitated the calculation of child-specific CL(int) based on knowledge of hepatic CYP2E1 protein levels. Toluene cytochrome P450 family 2 subfamily E member 1 Homo sapiens
3 The resulting model was used to simulate the blood concentration profiles in children exposed by inhalation, to 1 ppm toluene for 24 h. For this exposure scenario, the area under the venous blood concentration vs. time curve (AUC) ranged from 0.30 to 1.01 microg/ml x h in neonates with low CYP2E1 concentration (<3.69 pmol/mg protein). Toluene cytochrome P450 family 2 subfamily E member 1 Homo sapiens