EFFECT OF SIMULTANEOUS DIDANOSINE ADMINISTRATION ON ITRACONAZOLE ABSORPTION IN HEALTHY-VOLUNTEERS

Study Objective. To investigate the effect of simultaneously administe red didanosine (ddI) on the absorption of a single dose of itraconazol e. Design. Randomized, crossover, unblinded single-dose pharmacokineti c study in healthy volunteers. Comparisons of itraconazole alone and i traconazole with simultaneous ddI were performed on days 1 and 15. Set ting. A university medical center. Patients. Seven healthy men and wom en. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions. Volunteers received a single 20 0-mg oral dose of itraconazole or itraconazole with concomitant oral d dI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evalu ated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's seru m concentration-time curve. A mean +/- SD peak serum itraconazole conc entration of 0.90 +/- 0.30 mu g/ml was observed at 3.0 +/- 0.7 hours w hen itraconazole was administered alone, compared with undetectable le vels in all patients during therapy with ddI. Conclusions. Simultaneou s oral administration of ddI significantly decreases absorption of itr aconazole. These drugs should not be administered concurrently