摘要
建立他克莫司（FK506）临床个体化给药的新模式．选择活体肝移植患者2例，术前确定患者CYP3A5的基因型，并结合FK506的药代动力学参数制定初步的给药方案；给药后用高效液相色谱串联质谱检测法（LC-MS／Ms）进行血药质量浓度监测，根据血药质量浓度、临床疗效、不良反应及合并用药情况调整FK506的后续给药方案．术前2例患者基因测序结果均为CYP3A5＊3／＊3型，属FK506慢代谢型，初始给药方案为0．045mg·kg^-1·d^-1,分2次服用．给药后血药质量浓度监测结果在7．20～19．46ng·mL^-1范围；术后2例患者ALT、AST、BUN、Cr等总体均呈逐渐下降趋势，提示移植肝脏未发生急性排异反应，功能逐渐恢复；出院建议FK506剂量调整为病例1：1mg，2次·d^-1；病例2：3．5mg，2次·d^-1．2例患者应用FK506个体化给药新模式获得满意的效果，为临床合理使用FK506提供了科学的依据和方法．
The aim was to establish a subject-based administration of tacrolimus （FK506） in the clinic. Prior to liver transplantation, preliminary dosage regimen was formulated according to CYP3A5 genotype of two living liver-transplantation patients and FK506 pharmacokinetics. After liver transplantation, blood FK506 was monitored with LC-MS/MS, dosage regimen adjusted according to blood concentration, curative effect, ADRs and drug interaction. Preliminary dose was 0.045 mg·kg^-1·d^-1（twice/day） because genotyping found the two patients being CYP3A5·3/·3 which indicates slow metabolism for FK506. Blood FK506 was found to be 7.20-19.46 ng·mL^-1. ALT, AST, BUN and Cr values indicated no acute rejection and a recovering transplanted liver. After discharge from hospital, patient 1 was kept on 1 mg·d^-1 and patient 2 3.5 mg·d^-1.
出处
《北京师范大学学报（自然科学版）》
CAS
CSCD
北大核心
2008年第3期255-258,共4页
Journal of Beijing Normal University(Natural Science)
