Effect of carbamazepine treatment on urinary 6-hydroxycortisol excretion in humans.

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By monitoring urinary 6-hydroxycortisol (6-OHF) excretion, the effect of carbamazepine (CBZ) administration on hepatic monooxygenase activity was investigated in 3 voluntreers and 3 patients and compared with that of rifampicin (RFP), one of the most potent enzyme-inducing agents. In every case, 6-OHF excretion in 3-hr urine after ingestion of 20 mg cortisol exceeded 500μg/day, which is considered an upper normal value. The percentage increase of urinary 6-OHF excretion following CBZ administration was 81 to 128% at the 7th day and 99 to 166% at the 14th day. This gradational increase of urinary 6-OHF excretion was accompanied by a corresponding decrease of CBZ plasma clearance, but not by significant elevation of plasma γ-glutamyltranspeptidase. The output of 6-OHF returned to control level 2 to 3 weeks after discontinuance of CBZ. The increase in 6-OHF excretion induced by CBZ appeared to be comparable to that by RFP. These results indicate that CBZ appears to have marked enzyme-inducing ability which may result in diminished efficacy of some drugs when coadministered, and that the enzyme-inducing effect of CBZ is as potent as that of RFP.
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