Osowski C L, Dix S P, Lin L S, Mullins R E, Geller R B, Wingard J R
Emory University Hospital, Atlanta, GA 30322, USA.
Transplantation. 1996 Apr 27;61(8):1268-72. doi: 10.1097/00007890-199604270-00026.
The purpose of this open-label, prospective study was to compare steady state concentrations and clearances of intravenously administered cyclosporine or tacrolimus with and without concomitant high-dose (400 mg/day) fluconazole in allogeneic BMT patients. Twenty-one patients were evaluable. The mean steady state cyclosporine and tacrolimus concentrations without fluconazole were 320.3 and 18.2 ng/ml and increased to 389.2 and 21.2 ng/ml, respectively, after the addition of fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) increase. The mean steady state clearance of cyclosporine and tacrolimus without fluconazole was 6.82 and 1.28 ml/min/kg, which decreased to 5.57 and 1.10 ml/min/kg with fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) decrease, respectively. The 21% difference in the cyclosporine concentration and clearance was not thought to be clinically significant. These results suggest that fluconazole's interaction with cyclosporine or tacrolimus may be a result of fluconazole's inhibition of gut metabolism, resulting in a greater extent of absorption.
这项开放标签的前瞻性研究旨在比较在异基因骨髓移植患者中，静脉注射环孢素或他克莫司在联合使用和不联合使用高剂量（400毫克/天）氟康唑时的稳态浓度和清除率。21名患者可进行评估。未使用氟康唑时，环孢素和他克莫司的平均稳态浓度分别为320.3和18.2纳克/毫升，添加氟康唑后分别增至389.2和21.2纳克/毫升，相应增加了21%（P = 0.031）和16%（P = 0.125）。未使用氟康唑时，环孢素和他克莫司的平均稳态清除率分别为6.82和1.28毫升/分钟/千克，使用氟康唑后降至5.57和1.10毫升/分钟/千克，相应降低了21%（P = 0.031）和16%（P = 0.125）。环孢素浓度和清除率21%的差异被认为无临床意义。这些结果表明，氟康唑与环孢素或他克莫司的相互作用可能是由于氟康唑抑制肠道代谢，导致吸收程度增加。
