With the usual dosage oral administration of itraconazole (ITRA) has been shown to achieve therapeutic levels only after several days of treatment. Using the oral liquid formulation the concept of a loading dose (with 4x 200 mg for 2 days) was combined with the use of metoclopramide to enhance absorption. This was followed by a dosage of 2x 200 mg per day. Patients with AML (n =9)or NHL(n = 1) and need for a prophylactic antimycotic were eligible. Metoclopramidewasadministered in a dose of 12mg approximately15min before ITRA oral solution. Patients were not restrained from eating during the study period. ITRA and hydroxy-itraconazole (HO-ITRA) was determined using a HPLC method. Samples were taken at 0, 14, 24, 38, 48, 62, 72, 86 and 96 h. The predetermined target concentration of >500 ng/mL was achieved in 9/10 patients after 6 doses. Only one female patient showed delayed absorption and reached 654 ng/mL only after >96 h. Steady state was reached in most patients after 48 h with trough levels around 800 ng/mL. 4-HO-ITRA levels were in the same range These results show, that with a loading dose of 4x 200 mg for 2 days given immediately after oral metoclopramide, therapeutic drug levels are achievable in the majority of patients. This is an approach, which is not only important for antifungal prophylaxis, but might also be useful for situations of empirical treatment. In a patient without prophylaxis, the initiation during the first days of fever will produce therapeutic levels well within the time range usually considered necessary for the empirical antifungal treatment.
Full conference title:
11th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 11th (2001)