Hydrocortisone secretion: production rate and pulse characterization by numerical deconvolution.
Based on serial blood sampling over 24 h, hydrocortisone was shown to be secreted episodically in the horse. The purpose of the present experiment was to characterize peaks and troughs by analyzing the instantaneous secretion rate profile obtained by a deconvolution technique rather than from the plasma concentration time profile. Kinetic parameters of hydrocortisone were determined following intravenous bolus and intravenous perfusion of hydrocortisone. Stationary and nonlinearity of hydrocortisone disposition were demonstrated. With the use of clearance values calculated from constant perfusion administration, the 24-h hydrocortisone production rate was estimated at 0.46 +/- 0.08 mg.kg-1.24 h-1. The instantaneous secretory profile was reconstituted by deconvoluting the plasma concentration profile using structural parameters determined from the bolus hydrocortisone administration. When this secretory profile was subjected to a pulse analysis program, the number of detected peaks was found to be 17.25 +/- 1.26 and the mean peak duration 34.01 +/- 5.52 min. The total duration of secretory activity was estimated at 582.5 +/- 63.97 min. By comparison, when the plasma concentration profile was analyzed directly, the number of peaks was only 10.0 +/- 1.41 but their mean duration was much longer, i.e., 105.25 +/- 21.24 min. The origin of these differences and the advantages and limits of deconvolution analysis are discussed.
Toutain
P L
PL
Station de Pharmacologie-Toxicologie, Institut National de la Recherche Agronomique, Toulouse, France.
Laurentie
M
M
Autefage
A
A
Alvinerie
M
M
D000818:Animals; D006736:Horses / Q000502:physiology*; D006854:Hydrocortisone / Q000378:metabolism* / Q000493:pharmacokinetics; D008432:Mathematical Computing; D008905:Minicomputers; D010507:Periodicity
D006854:Hydrocortisone