Ohlman S, Zilg H, Schindel F, Lindholm A
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden.
Transpl Int. 1994;7(1):5-10. doi: 10.1007/BF00335656.
The pharmacokinetics of the novel immunosuppressant 15-deoxyspergualin (DSG) were studied in five renal transplant patients who participated in a dose-finding study for the treatment of renal graft rejection. DSG, in a dose of 4 or 6 mg/kg per day, was given in a 3-h i.v. infusion for 5 days, in combination with a 4-day course of i.v. methylprednisolone. Analyses of DSG in plasma and urine were performed by high-performance liquid chromatography (HPLC). Plasma samples were taken up to 12 h following infusion on treatment day 2 and again on day 4 or 5. Urine was collected during the infusion and up to 12 h following the infusion. DSG was rapidly eliminated from the plasma in an apparently biexponential manner. The mean t1/2 alpha was 0.5 h (range 0.1-1.1 h) and the mean t1/2 beta 2.4 h (range 1.0-5.9 h). The mean Cmax was 4117 ng/ml (range 1944-7166 ng/ml) and the mean AUC 12505 ng.ml-1 x h (range 5642-24436 ng.ml-1 x h). Clearance ranged from 375 to 945 ml/min (mean 653 ml/min) and volume of distribution ranged from 0.2 to 1.4 l/kg (mean 0.7 l/kg). A small fraction (mean 1.6%, range 0.1%-2.7%) of the DSG dose given was excreted unmetabolized in the urine. The amount of DSG in the urine correlated strongly to renal function (P = 0.0019). Pharmacokinetics were otherwise not affected by the degree of renal function. There were no significant differences in the pharmacokinetic determinants and no accumulation of the drug on study day 4 or 5, as compared to day 2.(ABSTRACT TRUNCATED AT 250 WORDS)
在五名参与肾移植排斥反应治疗剂量探索研究的肾移植患者中，对新型免疫抑制剂15 - 去氧精胍菌素（DSG）的药代动力学进行了研究。DSG剂量为每日4或6mg/kg，静脉输注3小时，共5天，并联合静脉注射甲泼尼龙4天。采用高效液相色谱法（HPLC）对血浆和尿液中的DSG进行分析。在治疗第2天输注后12小时内以及第4天或第5天再次采集血浆样本。在输注期间及输注后12小时内收集尿液。DSG以明显的双指数方式从血浆中迅速消除。平均t1/2α为0.5小时（范围0.1 - 1.1小时），平均t1/2β为2.4小时（范围1.0 - 5.9小时）。平均Cmax为4117ng/ml（范围1944 - 7166ng/ml），平均AUC为12505ng·ml-1·h（范围5642 - 24436ng·ml-1·h）。清除率范围为375至945ml/分钟（平均653ml/分钟），分布容积范围为0.2至1.4l/kg（平均0.7l/kg）。给予的DSG剂量中有一小部分（平均1.6%，范围0.1% - 2.7%）以未代谢形式经尿液排泄。尿液中DSG的量与肾功能密切相关（P = 0.0019）。否则，药代动力学不受肾功能程度的影响。与第2天相比，在第4天或第5天药代动力学决定因素无显著差异，且药物无蓄积。（摘要截断于250字）
