Neumayer H H, Budde K, Färber L, Haller P, Kohnen R, Maibücher A, Schuster A, Vollmar J, Waiser J, Luft F C
5th Medical Clinic for Nephrology, University Hospital Charité, Humboldt-University, Berlin, Germany.
Clin Nephrol. 1996 May;45(5):326-31.
We switched 302 renal transplant patients from the conventional to a new microemulsion formulation of cyclosporine, to study the latter's safety and efficacy. We used a simple 1:1 conversion of the patient's total daily dose. We measured trough drug levels as well as serum creatinine, liver enzymes, uric acid, and blood pressure values at baseline and at days 4, 8, 15, 29, and months 3, 6 and 12 after drug substitution. Dose adjustments directed at trough levels 80-120 ng/ml were performed, starting at day 8. Within the 12-month observation period, the cyclosporine dose was reduced by 14.7% (204 +/- 60 mg/day baseline vs 174 +/- 51 mg/day after conversion, p < or = 0.001). By day 8, the 1:1 dosage conversion resulted in a modest mean increase in drug trough levels (114 ng/ml baseline vs 120 ng/ml, p < or = 0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (p < or = 0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (p < or = 0.05). After one month, drug trough levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months (102 +/- 33 ng/ml, p < or = 0.001). Plasma creatinine values decreased to below baseline by month 6 (p < or = 0.001) and month 12 (p < or = 0.001). Twenty-four (8%) biopsy proven rejection episodes and 7 cases of cyclosporine attributed nephrotoxicity occurred in these 302 patients within these 12 months. We conclude, that a 1:1 conversion from conventional to the microemulsion form of cyclosporine is efficacious and safe. However, we advise an initial 10% decrease in dose reduction in those patients whose trough levels are in the high-normal range.
我们将302例肾移植患者从常规环孢素制剂转换为新的微乳剂配方，以研究后者的安全性和有效性。我们采用患者每日总剂量1:1的简单转换方式。在基线以及药物替换后的第4、8、15、29天和第3、6、12个月，我们测量了谷值药物水平以及血清肌酐、肝酶、尿酸和血压值。从第8天开始，针对80 - 120 ng/ml的谷值水平进行剂量调整。在12个月的观察期内，环孢素剂量降低了14.7%（基线时为204±60 mg/天，转换后为174±51 mg/天，p≤0.001）。到第8天，1:1的剂量转换使药物谷值水平出现适度的平均升高（基线时为114 ng/ml，转换后为120 ng/ml，p≤0.01）。这种升高伴随着血清肌酐浓度的增加、计算得出的肌酐清除率的降低以及尿酸值的升高（p≤0.05）。肝酶保持不变，而收缩压和平均动脉血压下降（p≤0.05）。1个月后，药物谷值水平降至基线（112 ng/ml）并维持到第6个月。12个月后显著降低（102±33 ng/ml，p≤0.001）。血浆肌酐值在第6个月（p≤0.001）和第12个月（p≤0.001）降至基线以下。在这302例患者的12个月内发生了24例（8%）经活检证实的排斥反应事件和7例环孢素所致肾毒性病例。我们得出结论，从常规环孢素制剂到微乳剂形式的1:1转换是有效且安全的。然而，对于谷值水平处于高正常范围的患者，我们建议初始剂量降低10%。
