[Example of active therapeutic follow-up: itraconazole]

The systematic fungal infections are very serious diseases, the crude mortality in invasive aspergillosis reaches 75 to 100 per cent. Systemic mycosis tends to develop in immunocompromised patients with subsequent physiopathological state, causing a risk of impairment in their digestive absorption potential; in addition these patients are polymedicated and the emergence of multiple drug interactions is frequent. Itraconazole is a very potent antifungal drug with large safety margin and the drug monitoring to maintain a satisfactory plasma level. Immunocompromised patients with suspected malabsorption and treated with oral capsule itraconazole were monitored during two years. In such difficult patients (approximately equal to 500 cases), the result has shown good trough steady-state plasma levels in 72 per cent and insufficient in 28 per cent of the observed patients. However concomitant treatments with antacids produce, in a lot of cases (approximately equal to 48 per cent), a noticeable decrease of the itraconazole availability for these patients. A training program was established to perform the analytical determination of itraconazole and hydroxyitraconazole in biological samples by HPLC method. Analytical validation procedures were associated to this training program which included 115 scientific, technical staff (pharmacists, biochemists ...) from 56 hospitals and institutes.