AJP - Endocrinology and Metabolism, Vol 254, Issue 1 E104-E112, Copyright © 1988 by American Physiological Society
A model of the distribution and metabolism of corticotropin-releasing factor
B. Candas, J. Lalonde and M. Normand
Departement de Physiologie, Faculte de Medecine, Universite Laval, Quebec City, Canada.
The aim of this study is the selection of the number of compartments
required for a model to represent the distribution and metabolism of
corticotropin-releasing factor (CRF) in rats. The dynamics of labeled rat
CRF were measured in plasma for seven rats after a rapid injection. The
sampling schedule resulted from the combination of the two D-optimal
sampling sets of times corresponding to both rival models. This protocol
improved the numerical identifiability of the parameters and consequently
facilitated the selection of the relevant model. A three-compartment model
fits adequately to the seven individual dynamics and better represents four
of them compared with the lower-order model. It was demonstrated, using
simulations in which the measurement errors and the interindividual
variability of the parameters are included, that his four-to-seven ratio of
data sets is consistent with the relevance of the three-compartment model
for every individual kinetic data set. Kinetic and metabolic parameters
were then derived for each individual rat, their values being consistent
with the prolonged effects of CRF on pituitary-adrenocortical secretion.
