肾移植术后早期国产环孢素药动学的临床研究

 目的:探讨肾移植受者术后早期服用国产环孢素的药动学变化特点。明确环孢素各时点血药浓度与时间-曲线下面积(AUC)的相关关系。方法:43例肾移植受者始服环孢素6mg·kg^-1.d^-1 7 d后，按不同品种分A组18例，B组15例，C组10例。3组分别于服药即刻，服药后1,2,3,4,5，6，8,10,12 h抽血查环孢素浓度（以C₀C₁C₂……C₁₂表示），比较不同品种 药动学的变化特点。然后，用逐步回归分析法计算环孢素的总体C₀、C₂、峰浓度C_max，达峰时间（T_max).AUC以及各种指标的 变异系数，并计算各浓度值与AUC的相关关系。结果:3种国产环孢素在使用相同剂量时，C₀,C₂,C_max,T_max，AUC差异均无 显著性，具有同质性。合并分析后，总体值C₀为（215.2±113.0)μg^-1，总体C_max=C₂为（1024.8± 378.7)μg^-1，达峰时间（2.0±0.9)h,平均2 h，AUC为（5106.4± 1471.8)μ·h·L^-1。抽血检测的10个时点浓度中，C₁、C₂、C₃、C₄、C₆与AUC的 相关性有显著性，其中C₂偏相关系数0.96最大，而变异系数(34.9%)相对较小。C₀不仅变弄系数(52.8%)较大，且与AUC 的相关性亦不显著。结论：国产环孢素总体峰浓度为C₂,与AUC具有较好的相关性，对AUC的变化影响大。可以将C₂作为 临床一个常规的环孢素浓度监测指标。

Pharmacokinetics studies of domestic cyclosporine in recipients of early phase after kidney transplantation

OBJECTIVE To investigate the pharmacokinetics parameters of domestic cyclosporine and determine the correlation between sequentially target CsA blood concentrations and AUC. METHODS 43 cases of kidney transplant recipients were grouped according to the different commercially available cyclosporine which they were taking. The whole blood CsA concentrations were assayed 7 days after oral administration with a dosage of 6 mg·kg^-1.d^-1. The blood samples drawn just prior to ingestion of the dose and subsequently at 1,2,3,4,5,6,8, 10, 12 h later were monitered with TDX. C₀, C₂, C_max，T_maxand AUC of each cyclosporine product were compared with each other and then calculated as a total. The correlationships between this sequentially CsA concentrations and AUC were also statistically analysed. RESULTS No significant differences for C₀ , C₂,C_max，T_maxand AUC between the cyclosporine products were observed. When analysed together,the general trough concentration was (215.2± 113.0)μg·L^-1,C₂ was (1048.0±378.7)μg·L^-1 served as the peak concentration(C_max），T_maxwas (2.0±0.9) h and AUC (5106.4 ± 1471.8 )μg·h·L^-1. Within the 10 individual CsA concentrations, C₁, C₂, C₃, C₄, C₆, were significantly correlated with AUC,of which PK of C₂ was the highest one. C₀ didn't significantly correlated with AUC. CONCLUSIONS Peak concentration of domestic-produced CsA was C₂ in total, which significantly correlated with and maximumly affected AUC. Co didn’t significantly correlated wit h AUC. We conclude that C₂ may also serve as a conventional parameter for domestic-produced CsA dosage adjustment in clinical practice.