FUNCTION OF THE ADRENAL-CORTEX DURING THERAPY WITH FLUCONAZOLE IN INTENSIVE-CARE PATIENTS

An impairment of cortisol synthesis can be assumed for the new antimyc otic fluconazole based on its chemical structure (triazole derivative) and mechanism of action (inhibition of ergosterol synthesis). In heal thy volunteers, however, no influence on steroid hormone production co uld be found. The present study was undertaken to clarify whether this is also true for critically ill, long-term patients in an intensive c are unit. The basal cortisol and adrenocorticotropic hormone (ACTH) le vels were determined by means of radioimmunoassay in 11 patients being treated with antimycotics at fixed times. Antimycotic treatment was c arried out using either fluconazole (n=6) or a combination of amphoter icin B and flucytosine (n=5) for 14 days. Seven days after cessation o f the treatment the above-mentioned hormones were again determined. Pa tients with the same baseline criteria who did not require antimycotic treatment (n=8) served as controls. During the entire study period ad equate cortisol synthesis was found after ACTH stimulation in all thre e patient groups. They all presented with relatively raised basal cort isol levels (range 16.4-31.0 mug dl-1) and an increase in ACTH-stimula ted cortisol synthesis from 31% (group ampho B/flucytosine) to 78% (gr oup fluconazole). The basal ACTH values were always within the normal range (9.2-16.4 pg ml-1). Neither the basal ACTH levels nor the basal cortisol levels as well as the cortisol levels determined after the AC TH test showed adrenocortical suppression in the patients of all three groups. Thus, according to the present results clinically relevant im pairment of cortisol synthesis after treatment with fluconazole can be excluded.