title: Carbamazepine-danazol drug interaction: its mechanism examined by a stable isotope technique.
abstract: Carbamazepine (CBZ) labeled with 15N was used to investigate the mechanism of its pharmacokinetic interaction with the antiestrogenic steroid danazol during treatment of a patient with epilepsy. Danazol led to a pronounced inhibition of CBZ metabolism. During danazol coadministration, CBZ elimination half-life increased from a pretreatment value of 11 to 24.3 h. Carbamazepine plasma clearance decreased from 57.7 to 23.2 ml/h/kg. Kinetic analysis of the plasma concentration-time curves and urinary excretion of [15N]trans-CBZ-diol revealed that danazol inhibited the epoxide-trans-diol pathway of carbamazepine metabolism. Observations in five other female patients confirm that the steady-state plasma concentrations of UCBZ increase between 50 and 100% during coadministration of danazol.
mesh_terms: D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002606:Charcoal; D003613:Danazol / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007700:Kinetics; D009587:Nitrogen Isotopes; D011245:Pregnadienes / Q000378:metabolism*
chemical_list: D009587:Nitrogen Isotopes; D011245:Pregnadienes; D002606:Charcoal; D002220:Carbamazepine; D003613:Danazol