摘要
目的探讨肾移植受者长期服用五酯胶囊提高血他克莫司（Tac）浓度的安全性和适应证。方法将Tac浓度谷值相当的移植肾功能稳定的受者，根据是否长期服用五酯胶囊分为五酯组（10例）和对照组（10例），比较两组间Tac药动学参数，并比较五酯胶囊对不同细胞色素P4503A5（CYP3A5）基因型受者服用Tac剂量的影响。结果五酯组服用五酯胶囊平均为31个月，平均Tac浓度谷值为6．3μg／L；对照组平均Tac浓度谷值为5．9μg／L。五酯组平均，Ihc浓度峰值和曲线下面积均略高于对照组，达峰时间稍延迟，但差异无统计学意义（P〉0．05）。CYP3A5＊1／＊3型在二组中均占60％，而对照组中＊1／＊3型受者的Tac剂量为（0．067±0．001）mg·kg^-1·d^-1，明显高于五酯组同型受者的（0．042±0．016）mg·kg^-1·d^-1，差异有统计学意义（P〈0．01）。＊1／＊1型受者在五酯组中占30％，其Tac剂量为（0．036±0．006）mg·kg^-1·d^-1，比＊1／＊3型受者减少更明显；平均剂量最低的为对照组＊3／＊3型受者，为（O．034±0．005）mg·kg^-1·d^-1。结论对大部分CYP3A5＊1基因型受者可以考虑应用五酯胶囊提升Tac浓度，尤其对CYP3A5＊1／＊1型受者。
Objective To determine the effect of Wuzhi capsule （WZ） on pharmacokinetics of Tacrolimus （Tac） in kidney transplant patients who have taken WZ to reduce the dose of Tac for a long term. Method Twenty stable renal transplant patients with similar trough level of Tac were divided into WZ group （n = 10） and control group （n = 10）. Whole blood concentrations of Tac at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h after the morning dose was determined. Estimated pharmacokinetic parameters were calculated and compared. Additionally, CYP3A5 genotypes of each patient were analyzed using Polymerase Chain Reaction Restriction Fragment Length Polymorphism to compare the effect of CPY3A5 genotypes and WZ on Tac dose requirement. Result Pharmacokinetics data showed that Co of Tac was 6. 3 μg/L in WZ group and 5. 9 μg/L in control group. The average peak time of Tac was similar （1.4 h in WZ group, and 1.3 h in control group, P〉0. 05）. Both the peak concentration of Tac and AUC0-12h of Tac were slightly higher in WZ group than in control group with the difference being not statistically significant. The frequency of CYP3A5 ＊ 1/＊ 3 genotype was 60% in both groups, while the average dose of Tac was reduced by 30% in WZ group as compared with control group （0. 042 mg·kg^-1 ·day^-1 , and 0. 067 mg·kg^-1 ·day^-1, P〈0. 01）. In WZ group, the average dose of Tac was even lower in carriers of ＊ 1/＊ 1 genotype （0. 036 mg·kg^-1 ·day^-1） than that in carriers of ＊ 1/＊ 3 genotype, which was close to the lowest dose requirement in the carriers of ＊ 3/＊ 3 genotype from the control group （0. 034 mg·kg^-1 ·day^-1 ）. Conclusion In kidney transplant patients with CYP3A5 ＊ 1 genotype, a long-term application of WZ to reduce the required tacrolimus dose is a generally safe way without significant changes in regular pharmacokinetics of tacrolimus. For patients with genotype of CYP3A5 ＊ 1/＊ 1, WZ is particularly suitable.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2014年第9期533-536,共4页
Chinese Journal of Organ Transplantation
基金
卫生行业科研专项基金（201302009）
关键词
肾移植
他克莫司
药代动力学
Kidney transplantation
Tacrolimus
Pharmacokinetics
