环孢素个体化给药方案评价与调整  

Evaluation and adjustment of individualized dosage regimen of cyclosporin

作　　者：孙增先[1] 赵利东[1] 周金玉[1] 张骞峰[1] 高山[1] 洪荣[1] 刘金永[1] 

机构地区：[1]连云港市第一人民医院临床药学研究中心,江苏连云港222002

出　　处：《中国医院药学杂志》2012年第23期1893-1897,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的:研究环孢素A(CsA)的药动学特征,精确计算CsA个体化给药剂量,对个体化给药方案进行评价和调整。方法:对12例C0超出目标范围(200～300μg.L-1)的血液科患者,在剂量调整前后分别测定其药动学参数,研究CsA的药动学特征及其判别方法,计算和评价CsA个体化给药方案。结果:本组患者的CsA剂量与浓度、AUC0-12不成比例,在消除相表现尤为显著,C0比值与剂量比值差异最大(P<0.01)。在CsA非线性代谢患者,用线性公式计算的预期剂量显著高于用非线性公式计算的结果(P<0.01),且用2个不同初始剂量及其对应的C0计算的预期剂量存在显著差异(P<0.01)。在CsA线性代谢患者,使用2个不同的初始剂量及其对应的C0计算的预期剂量没有差异(P>0.05)。结论:C0比值判别CsA药动学特征最为灵敏。大部分患者的CsA代谢属于非线性代谢,应该使用非线性公式来精确调整剂量。CsA药动学特征的判别和计算模型的选择对CsA个体化剂量的评价和精确调整是非常重要的。OBJECTIVE To study the pharmacokinetic properties of cyclosporin A （CsA）, calculate accurately the best indi vidualized CsA dose, evaluate and adjust the individualized dosage regimen of CsA. METHODS Pharmacokinetic parameters of CsA were measured before and after dose adjustment respectively for 12 cases of patients whose G0 beyond the target range （200 - 300/,g· L- 1 ） in the department of hematology. CsA pharmacokinetic properties and its judgment methods were studied. Individualized dosage regimen of CsA was calculated and evaluated. RESULTS The dose and concentration, AUG0-12 of CsA was not proportion in this group of patients, and it was particularly significant in the elimination phase. The difference between C0 ratio and dose ratio was the maximum （P〈0. 01）. In the nonlinear metabolic patients of CsA, the expected doses that were calculated by linear formula were much higher than the results that were calculated by nonlinear formula （P〈0. 01 ）, and the expected doses that were calculated by two different initial doses and the corresponding C0 were significantly different （P〈0. 01）. In the linear metabolic patients of CsA, the expected doses that were calculated by two different initial doses and the corresponding C0 made no difference （P〉0. 05）. CONCLUSION C0 ratio was the most sensitive to judge pharmacokinetic properties of CsA. The CsA metabolism of the majority of patients belongs to nonlinear metabolism, so nonlinear formula should be adopted to adjust the doses accurately. The judgement of CsA pharmacokinetic properties and the choice of the calcu lation model are very important for the evaluation and accurate adjustment of the individualized CsA doses,

关 键 词：环孢素A 个体化给药方案 药动学特征 线性动力学 非线性动力学 

分 类 号：R969.1[医药卫生—药理学]