Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency

Thomson, A.H. and Devers, M.C. and Wallace, A.M. and Grant, D. and Campbell, K. and Freel, M. and Connell, J.M.C. (2007) Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency. Clinical Endocrinology, 66 (6). pp. 789-796. ISSN 0300-0664 (https://doi.org/10.1111/j.1365-2265.2007.02812.x)

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Abstract

The best method for determining hydrocortisone replacement therapy is not well defined. This study aimed to assess interindividual variability in cortisol pharmacokinetics and to investigate whether measurement of salivary cortisol provides a useful alternative to plasma concentration measurements. Patients Twenty-seven patients with primary or secondary adrenal insufficiency who had been on stable replacement therapy for at least 3 months. Cmax ranged from 715 to 8313 nmol/l, area under the curve (AUC) from 1112 to 12 177 nmol h/l and cortisol clearance had a median (range) of 0·267 (0·076-0·540) l/h/kg. After oral administration, Cmax ranged from 422 to 1554 nmol/l, AUC 1081-5471 nmol h/l and oral clearance had a median (range) of 0·267 (0·081-0·363) l/h/kg. There was no clear relationship between paired saliva and plasma cortisol concentrations after IV or oral dosing. Plasma and salivary AUC2−8 h after IV administration were highly correlated (r2 = 0·77) but differences between predicted and measured plasma AUCs ranged from 3% to 90%. There was a poor correlation between plasma and saliva AUC2−6 h after oral administration (r2 = 0·16). The wide interindividual variability in plasma and salivary profiles of cortisol following the administration of IV and oral hydrocortisone to patients with adrenal insufficiency and the poor correlation between salivary and plasma measurements suggest that salivary cortisol measurements cannot be used for individual hydrocortisone dosage adjustment.

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