Vol. 281, Issue 5, E946-E956, November 2001
A nonlabeled method to evaluate cortisol production rate by
modeling plasma CBG-free cortisol disposition
N.
Picard-Hagen1,
V.
Gayrard1,
M.
Alvinerie2,
H.
Smeyers1,
R.
Ricou1,
A.
Bousquet-Melou1, and
P. L.
Toutain1
1 Unité associée Institut National de la
Recherche Agronomique de Physiopathologie et Toxicologie
Expérimentales, Ecole Nationale Vétérinaire de
Toulouse, 31076 Toulouse; and 2 Institut National de la
Recherche Agronomique Station de Pharmacologie, 31300 Toulouse, France
This study aimed to
develop a nonlabeled method for the measurement of cortisol production
rate to evaluate adrenal function. The cortisol production rate
determination requires that of cortisol clearance, which is not a
parameter but a variable resulting from the saturable binding of
cortisol to corticosteroid-binding globulin (CBG). Our method is based
on evaluation of the plasma clearance of the CBG-free cortisol
fraction. This parameter was evaluated from a pharmacokinetic model of
total plasma cortisol disposition that takes into account specific
binding of the corticoid to CBG in the plasma. We have shown that the
CBG-free cortisol kinetics and CBG-binding parameters thus evaluated
are not statistically different from those obtained by the
radioisotopic method and equilibrium dialysis, suggesting that the
plasma CBG-free cortisol clearance is independent of the total plasma
cortisol concentrations and represents the actual parameter of cortisol
elimination. We validated this modeling approach by using it to
calculate the in vivo entry rate of cortisol mimicked by the perfusion
of cortisol at a known rate.
cortisol disposition; ovine; corticosteroid-binding globulin
