Serum levels of ketoconazole in bone marrow transplanted patients.
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 per day in a single dose) as antifungal prophylaxis for 6 months. 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 h or 6 h after ingestion. Most measurements showed appropriate levels (maximum levels greater than 1 mg/l) even after the third week post transplantation. With the exception of severe acute GVH disease (1 patient), the ketoconazole absorption was adequate in minor or mild GVH disease (6 patients) and in chronic GVH disease (2 patients). In four patients ketoconazole absorption was compared with gut absorption tests (Schilling's test, Iron absorption test, xylose test): In all patients the maximum serum levels of ketoconazole were correct, even in three patients with abnormal gut absorption tests. In this series, no life-threatening mycotic infection occurred, and the three deaths observed showed no mycotic infection.
D000328:Adult; D000935:Antifungal Agents / Q000097:blood*; D001681:Biological Assay; D016026:Bone Marrow Transplantation; D002176:Candida albicans / Q000378:metabolism; D006087:Graft vs Host Reaction; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism; D007654:Ketoconazole / Q000097:blood*; D007938:Leukemia / Q000097:blood / Q000628:therapy*; D014994:Xylose / Q000378:metabolism
D000935:Antifungal Agents; D014994:Xylose; D007501:Iron; D007654:Ketoconazole