Development of a Physiologically Based Pharmacokinetic Model for the Anesthetics Halothane, Isoflurane, and Desflurane in the Pig (SUS SCROFA)
Interim rept. Sep-Nov 1998
MANTECH GEO-CENTERS JOINT VENTURE DAYTON OH
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The pig has been commonly used in biomedical research studies because of similarities between humans and pigs in various aspects of structure and function. Under consideration is its use for studying the effects of long-term low-level exposure to organophosphates. In spite of the wide use of the pig as an experimental subject there has been no prior attempt to develop a physiologically based pharmacokinetic PBPK model to allow linking of external exposure to internal concentrations at sites of effects resulting from xenobiotic exposures. A model was developed with the potential of tracking chemical concentrations in brain, kidney, liver, fat, arterial and venous blood, muscleskin, and other generally well perfused body organs. As an initial attempt at validating the model, the literature was explored for studies that contained data that were in a form suitable for modeling. Such a study was one in which pigs had been exposed to the anesthetics halothane, isoflurane and desflurane and exhaled concentrations of these chemicals were monitored. These data were used in the initial model validation. The model did an adequate job of simulating the data. Further development and reining of the model will depend on planning actual studies with defined endpoints of interest.
- Medicine and Medical Research