{"paper_id":"44265e27-9ad9-4031-8b76-36ed9e393dfd","body_text":"Carbamazepine-Danazol Drug Interaction\nIts Mechanism Examined by a Stable Isotope Technique\n- G. Krämer\n- M. Theisohn\n- G. E. von Unruh\n- M. Eichelbaum\nSummary:\nCarbamazepine (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.","source_license":"CC0","license_restricted":false}