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Hypercortisolemia decreases dexamethasone half-life in rabbit
P E Stokes1, P M Stoll, J H Schluger
1Department of Psychiatry, Cornell Medical College, New York, NY, USA.
Journal of Psychiatric Research
|October 24, 2002
Summary
High cortisol levels, or hypercortisolemia, shorten the body's processing time for dexamethasone. This finding may explain lower dexamethasone levels observed in individuals with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity.
Area of Science:
- Endocrinology
- Pharmacokinetics
- Neuroscience
Background:
- Dexamethasone pharmacokinetics are linked to hypothalamic-pituitary-adrenal (HPA) axis activity.
- Lower plasma dexamethasone levels are reported in psychiatric patients with dexamethasone suppression test (DST) nonsuppression.
- DST nonsuppression indicates HPA axis hyperactivity and is associated with increased cortisol and lower dexamethasone levels.
Purpose of the Study:
- To investigate the hypothesis that hypercortisolemia accelerates dexamethasone clearance from plasma.
- To study the effect of sustained hypercortisolemia on dexamethasone half-life in rabbits.
Main Methods:
- Induced sustained hypercortisolemia in rabbits via intramuscular hydrocortisone acetate.
- Measured dexamethasone half-life before, during, and after the hypercortisolemia period.
- Included a control group receiving saline injections.
Main Results:
- Mean dexamethasone half-life significantly decreased from 1.92 hours at baseline to 1.17 hours during induced hypercortisolemia (P < 0.001).
- No significant change in dexamethasone half-life was observed in saline-treated control rabbits.
- Dexamethasone half-life returned to baseline levels 88 days after the intervention.
Conclusions:
- Pronounced hypercortisolemia significantly decreases dexamethasone half-life in rabbits.
- Increased circulating cortisol levels likely induce hepatic enzymes that metabolize dexamethasone.
- Lower plasma dexamethasone levels in DST nonsuppressors may reflect the impact of hypercortisolemia.
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