Summary:A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (C min ) and 4 h later (C max ) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of C min ITRA and OH-ITRA, respectively, were 287 ؎ 109 ng/ml and 629 ؎ 227 ng/ml at day ؊1 and 378 ؎ 147 ng/ml and 725 ؎ 242 ng/ml at day +1. The maximum C min values were observed at day +3. Six patients at day ؊1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases. Keywords: pharmacokinetics; itraconazole solution; BMT; TBI Prophylaxis and treatment of systemic fungal infections in patients undergoing allogeneic bone marrow transplant (BMT) remain important issues. Broad spectrum antifungals with a low toxicity and good bioavailability are being sought. Ideally, orally administered medications given to prevent invasive aspergillosis should provide a systemic effect. However several factors are likely to impair bioavailability of orally administered medications in allogeneic BMT patients: nausea and vomiting mainly during conditioning regimen period, mucositis during aplasia and acute graft-versus-host disease (GVHD) later.Itraconazole, a triazole broad spectrum antifungal 1,2 is presently marketed as capsules. Important variations in plasma itraconazole concentrations observed in patients, compared with healthy volunteers, 3 are related to individual conditions of drug absorption, thereby justifying plasma measurements. A plasma concentration of unchanged itraconazole (ITRA) у250 ng/ml is considered necessary to obtain a therapeutic effect on Aspergillus. 4 However, since hydroxy-itraconazole (OH-ITRA) has a similar antifungal effect to unchanged ITRA, 5 the active fraction is represented by the sum of unchanged ITRA and its active metabolite OH-ITRA with an effective total level of about 1000 ng equivalents/ml. This effective level could be estimated from the effective plasma levels of unchanged ITRA (Ϸ250 ng/ml) 4,6 and metabolic ratio in human plasma between ITRA and OH-ITRA ([OH-ITRA]/[ITRA] Ϸ2). 7 However the capsule formulation is of limited use in allogeneic BMT: its bioavailability is reduced when administered under fasting conditions and when coadministered with antacids. 8 Itraconazole oral solution is a new formulation where ITRA is solub...
Summary:Two male patients with non-Hodgkin's lymphoma (NHL, follicular NHL, diffuse large B cell NHL, both in 2nd complete remission) and one female patient with acute myeloid leukemia in 1st complete remission developed arthralgias and enthesopathy following autologous stem cell transplantation. In 2/3 patients, sacroiliitis could be demonstrated on X-ray. In both patients, the rheumatic symptoms were classified as manifestations of a spondylarthropathy. All three patients were subsequently shown to be HLA-B27-positive. The patients were successfully treated with non-steroidal anti-inflammatory drugs. The differential diagnosis of joint pain following autologous stem cell transplantation should include HLA-B27-associated spondylarthropathies in addition to the more commonly seen bone and joint pain due to immobilization and medication. Bone Marrow Transplantation (2000) 26, 673-675.
A 32-year-old female patient is described who suffered from common symptoms such as Raynaud's phenomenon and swollen fingers, high titers of antibodies to U1RNP, SLE-like findings, scleroderma-like findings and polymyositis-like findings. A diagnosis of mixed connective tissue disease (Sharp-syndrome) was established. In addition, the patient had antibodies against cardiolipin, thrombocytopenia, recurrent fetal loss and a history of deep venous thrombosis of her left leg which is typical for an antiphospholipid syndrome. The symptoms dry eyes and dry mouth pointed at secondary Sjögren's syndrome. The diagnosis of these disease entities and the therapeutic regimens are described and discussed.
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