Lack of enzyme induction with oxcarbazepine (600 mg daily) in healthy subjects.
1. Oxcarbazepine (OXC), the 10-keto analogue of carbamazepine (CBZ), has similar anticonvulsant efficacy and possibly improved patient tolerability. Unlike CBZ, it is metabolised by reduction and may not induce hepatic monooxygenase enzymes. 2. Serum concentrations of OXC and its active metabolite 10-OH-carbazepine (10-OH-CZ) were followed after a single 300 mg dose and during and after 300 mg OXC twice daily for 29 doses in eight healthy male volunteers. 3. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, sex hormone binding globulin (SHBG) levels and circulating androgens were measured as indices of hepatic enzyme induction before, during and after treatment with OXC. 4. Elimination half-lives (mean +/- s.e. mean) of 10-OH-CZ were unaltered by 2 weeks' therapy with OXC (before 11.3 +/- 1.1 h; after 13.9 +/- 3 h). Trough plasma concentrations of 10-OH-CZ at steady-state (31 +/- 2.2 mumol l-1) were higher than predicted (16.5 +/- 4 mumol l-1). 5. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, SHBG levels and circulating androgens were unaltered by treatment with OXC. 6. OXC (600 mg daily) does not induce hepatic monooxygenase enzymes and so is likely to have more predictable dose-concentration relationships and to produce fewer physiological and pharmacological interactions than CBZ.
Larkin
J G
JG
Epilepsy Research Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow.
McKee
P J
PJ
Forrest
G
G
Beastall
G H
GH
Park
B K
BK
Lowrie
J I
JI
Lloyd
P
P
Brodie
M J
MJ
D000328:Adult; D000983:Antipyrine / Q000097:blood; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects*; D006207:Half-Life; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D000078330:Oxcarbazepine; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D006728:Hormones; D012738:Sex Hormone-Binding Globulin; D002220:Carbamazepine; C001380:6 beta-hydroxycortisol; D006899:Mixed Function Oxygenases; D000983:Antipyrine; D000078330:Oxcarbazepine; D006854:Hydrocortisone