SERUM LEVELS OF KETOCONAZOLE IN BONE-MARROW TRANSPLANTED PATIENTS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 25  (4) , 241-244
Abstract
Seven patients with acute leukemia were treated by allogenic bone marrow transplantation from HLA matched sibling. The conditioning regimen was classical, using cyclophosphamide and total body irradiation, followed by methotrexate. All patients were given ketoconazole (400 mg/day in a single dose) as antifungal prophylaxis for 6 mo. Serum ketoconazole levels were measured using the inhibition assay of mycotic culture in gelose, and they were studied at 0, 1, 2, 4 and 6 h after ketoconazole ingestion and repeated serially after bone marrow transplantation. In these transplanted patients, absorption of ketoconazole could be delayed, with the maximum levels at 4 or 6 h after ingestion. Most measurements showed appropriate levels (maximum levels > 1 mg/l) even after the 3rd wk posttransplantation. With the exception of severe acute GVH [graft vs. host] disease (1 patient), the ketoconazole absorption was adequate in minor or mild GVH disease (6 patients) and in chronic GVH disease (2 patients). In 4 patients ketoconazole absorption was compared with gut absorption tests (Schilling''s test, Fe absorption test, xylose test): in all patients, the maximum serum levels of ketoconazole were correct, even in 3 patients with abnormal gut absorption tests. In this series, no life-threatening mycotic infection occurred, and the 3 deaths observed showed no mycotic infection.