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

Abstract：

OBJECTIVE: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. DESIGN:Intravenous (IV) and oral crossover. PATIENTS:Twenty-seven patients with primary or secondary adrenal insufficiency who had been on stable replacement therapy for at least 3 months. MEASUREMENTS:Plasma and salivary concentrations of cortisol were measured up to 8 h following administration of hydrocortisone. RESULTS:After IV administration, 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 AUC(2-8 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 AUC(2-6 h) after oral administration (r2 = 0.16). CONCLUSIONS: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.

journal_name

Clin Endocrinol (Oxf)

journal_title

Clinical endocrinology

authors

Thomson AH,Devers MC,Wallace AM,Grant D,Campbell K,Freel M,Connell JM

doi

10.1111/j.1365-2265.2007.02812.x

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

789-96

issue

eissn

0300-0664

issn

1365-2265

pii

CEN2812

journal_volume

pub_type

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