采用高效液相色谱-质谱联用（h.p.l.c.-MS）和微粒酶免疫分析法（MEIA）测定7例肝移植患者首次给药后FK506（他克莫司）及其代谢物的血药浓度。
Measurement of blood concentrations of FK506 (tacrolimus) and its metabolites in seven liver graft patients after the first dose by h.p.l.c.-MS and microparticle enzyme immunoassay (MEIA).
作者信息
Gonschior A K, Christians U, Braun F, Winkler M, Linck A, Baumann J, Sewing K F
机构信息
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
出版信息
Br J Clin Pharmacol. 1994 Dec;38(6):567-71. doi: 10.1111/j.1365-2125.1994.tb04398.x.
Abstract
- Blood and urine concentrations of the macrolide immunosuppressant FK506 and its metabolites were measured in seven orthotopic liver transplant patients after the first oral dose of FK506 (0.04 +/- 0.02 mg kg-1) used as primary immunosuppressant. A specific h.p.l.c.-MS assay was used, allowing the measurement of parent drug and eight metabolites. Results were compared with those obtained using a microparticle enzyme immunoassay (MEIA). 2. Blood drug concentrations were described by an open two compartment model with first-order absorption giving the following mean data: tmax: 1.9 (h), Cmax: 17.4 (microgram l-1), AUC: 328.1 (microgram l-1 h), t1/2,1: 0.74 (h). The terminal elimination half-life was estimated at about 26 h using the h.p.l.c.-MS assay. 3. The metabolites found in blood were demethyl-FK506 and demethyl-hydroxy-FK506, while in urine FK506 and eight of its metabolites were detected.
摘要
- 对7例原位肝移植患者在首次口服作为主要免疫抑制剂的大环内酯类免疫抑制剂FK506（0.04±0.02mg/kg-1）后，测定其血液和尿液中FK506及其代谢产物的浓度。采用一种特定的高效液相色谱-质谱分析法，可测定母体药物和8种代谢产物。将结果与使用微粒酶免疫测定法（MEIA）获得的结果进行比较。2. 血药浓度用具有一级吸收的开放二室模型描述，得出以下平均数据：达峰时间：1.9（小时），峰浓度：17.4（微克/升），曲线下面积：328.1（微克/升·小时），分布相半衰期：0.74（小时）。使用高效液相色谱-质谱分析法估计终末消除半衰期约为26小时。3. 在血液中发现的代谢产物为去甲基-FK506和去甲基-羟基-FK506，而在尿液中检测到FK506及其8种代谢产物。
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