Oxcarbazepine accelerates cortisol elimination via cytochrome P450 3A4 induction

• Published in: Archives of disease in childhood Vol. 95; no. 12; p. 1065
• Main Authors: Högler, W, Wudy, S A, Luef, G, Hartmann, M F, Rauchenzauner, M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01.12.2010; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Addison Disease - complications; Addison Disease - drug therapy; Addison Disease - metabolism; Addison's disease; Adolescent; Adult; Anticonvulsants - pharmacology; Biological and medical sciences; Carbamazepine - analogs & derivatives; Carbamazepine - pharmacology; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP3A - biosynthesis; Drug Interactions; Drug therapy; Enzyme Induction - drug effects; Epilepsy; Epilepsy, Temporal Lobe - complications; Epilepsy, Temporal Lobe - drug therapy; Epilepsy, Temporal Lobe - metabolism; General aspects; Hormones; Humans; Hydrocortisone - pharmacokinetics; Logical Thinking; Male; Medical sciences; Metabolism; Miscellaneous; Oxcarbazepine; Patient outcomes; Patients; Physical Health; Physiological aspects; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Scientific Concepts; Standard scores; Steroid hormones; Steroids; Young Adult; Human; Corticosteroid; Pediatrics; Enzyme; Steroid hormone; Induction; Cytochrome P450; Antiinflammatory agent; Elimination; Anticonvulsant; Cortisol; Hydrocortisone; Glucocorticoid; Oxcarbazepine; Adrenal hormone; Triggering; Child; Public health
• ISSN: 0003-9888; 1468-2044; 1468-2044
• DOI: 10.1136/adc.2009.167361

Oxcarbazepine (OXC) induces cytochrome CYP3A4 activity, lowering female sex steroid concentrations. To date, similar effects on corticosteroid concentrations have not been reported. The observation of an adolescent boy with Addison's disease requiring high hydrocortisone replacement doses while on OXC for epilepsy led us to investigate effects of OXC on CYP3A4 induction and steroid metabolism. Six young epileptic men on OXC monotherapy and six controls collected 24-h urines and had blood taken for steroid analysis. Accelerated cortisol elimination was confirmed by greater relative 24-h urinary 6-hydroxycortisol/cortisol excretion (4.67 (1.25) µg/day vs controls 2.32 (0.5) µg/day, p=0.001). Patients on OXC had lower serum oestradiol and dehydroepiandrosterone sulphate levels, but only tendencies remained after age adjustment. This study shows that OXC-induced CYP3A4 activity increases cortisol elimination. The effect is small in subjects with healthy adrenals. However, caution is warranted for patients with adrenal failure on high doses of OXC where choosing an alternative anticonvulsant may be advisable.