Oxcarbazepine accelerates cortisol elimination via cytochrome P450 3A4 induction.
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.
Department of Endocrinology, Birmingham Children's Hospital, Birmingham, UK. wolfgang.hogler@bch.nhs.uk
W
W
Högler
S A
SA
Wudy
G
G
Luef
M F
MF
Hartmann
M
M
Rauchenzauner
D000224:Addison Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D008297:Male; D000078330:Oxcarbazepine; D055815:Young Adult
D000927:Anticonvulsants; D002220:Carbamazepine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000078330:Oxcarbazepine; D006854:Hydrocortisone