Sagedal S, Asberg A, Hartmann A, Bergan S, Berg K J
Department of Internal Medicine, National Hospital, Oslo, Norway.
Clin Transplant. 1998 Dec;12(6):553-6.
Glipizide is an oral antidiabetic drug that has been used in the treatment of post-transplant diabetes mellitus (PTDM). However, a published case report has indicated a possible interaction of glipizide with cyclosporine (CsA) pharmacokinetics in two renal transplant (tx) patients. The aim of this open prospective study was to investigate whether glipizide interacts with CsA pharmacokinetics in renal tx patients with PTDM.
Eleven renal tx patients (29-74 years of age) with PTDM who received Sandimmun Neoral as part of their immunosuppressive therapy were investigated. No patients had suffered any significant rise in serum creatinine (20%) from any cause over the last 2 wk before the study. Mean S-creatinine was 137 mumol/L (87-220). The mean CsA dose and whole blood concentration remained unchanged during the study. CsA whole blood concentrations were monitored over 12 h in all patients in random order, both on and off glipizide treatment. Blood samples were drawn immediately before the morning dose of CsA was given (trough) and 0.5, 1, 1.5, 2, 3, 4, 6 and 12 h after administration.
Whole blood trough CsA concentration was not altered by glipizide treatment, 256 +/- 76 micrograms/L off and 242 +/- 73 micrograms/L (mean +/- SD) with glipizide coadministration. The area under the curve (AUC) and terminal half-life of CsA remained unchanged with glipizide treatment: 6391 +/- 1483 micrograms/L per h and 7.3 +/- 1.5 h without; and 6279 +/- 1601 micrograms/L per h and 7.1 +/- 1.8 h with glipizide, respectively. No change in the CsA peak concentration (Cmax) was observed: 1507 +/- 406 micrograms/L without and 1469 +/- 538 micrograms/L with glipizide coadministration.
CsA pharmacokinetics is not significantly altered by glipizide coadministration.
格列吡嗪是一种口服抗糖尿病药物，已用于治疗移植后糖尿病（PTDM）。然而，一份已发表的病例报告指出，在两名肾移植患者中，格列吡嗪与环孢素（CsA）的药代动力学可能存在相互作用。这项开放性前瞻性研究的目的是调查格列吡嗪在患有PTDM的肾移植患者中是否与CsA药代动力学相互作用。
对11名患有PTDM的肾移植患者（年龄29 - 74岁）进行了调查，这些患者接受新山地明作为免疫抑制治疗的一部分。在研究前的最后2周内，没有患者因任何原因出现血清肌酐显著升高（20%）。平均血清肌酐为137μmol/L（87 - 220）。在研究期间，CsA的平均剂量和全血浓度保持不变。所有患者均以随机顺序在服用和未服用格列吡嗪治疗时对CsA全血浓度进行12小时监测。在早晨服用CsA剂量之前（谷值）以及给药后0.5、1、1.5、2、3、4、6和12小时采集血样。
格列吡嗪治疗未改变CsA全血谷值浓度，未服用格列吡嗪时为256±76μg/L，联合使用格列吡嗪时为242±73μg/L（平均值±标准差）。格列吡嗪治疗后，CsA的曲线下面积（AUC）和终末半衰期保持不变：未服用时分别为6391±1483μg/L·h和7.3±1.5小时；服用格列吡嗪时分别为6279±1601μg/L·h和7.1±1.8小时。未观察到CsA峰值浓度（Cmax）有变化：未服用时为1507±406μg/L，联合使用格列吡嗪时为1469±538μg/L。
联合使用格列吡嗪不会显著改变CsA的药代动力学。
