EXAMPLE OF ACTIVE THERAPEUTIC DRUG-MONITO RING - ITRACONAZOLE

The systematic fungal infections are very serious diseases, the crude mortality in invasive aspergillosis reaches 75 to 100 per cent. System ic mycosis tends to develop in immunocompromised patients with subsequ ent physiopathological state, causing a risk of impairment in their di gestive absorption potential; in addition these patients are polymedic ated and the emergence of multiple drug interactions is frequent. Itra conazole is a very potent antifungal drug with large safety margin and the drug monitoring to maintain a satisfactory plasma level. Immunoco mpromised patients with suspected malabsorption and treated with oral capsule itraconazole were monitored during two years. In such difficul t patients (approximate to 500 cases), the result has shown good troug h steady-state plasma levels in 72 per cent and insufficient in 28 per cent of the observed patients. However concomitant treatments with an tiacids produce, in a lot of cases (approximate to 48 per cent), a not iceable decrease of the itraconazole availability for these patients. A training program was established to perform the analytic determinati on of itraconazole and hydroxyitraconazole in biological samples by HP LC method. Analytical validation procedures were associated to this tr aining program which included 115 scientific, technical staff (pharmac ists, biochemists...) from 65 hospitals and institutes.