Tacrolimus의 혈중농도측정법 비교 및 간이식환자에서의 집단 약동학

Comparison of Analytical Methods of Tacrolimus in Plasma and Population Pharmacokinetics in Liver Transplant Recipients

  • 김은영 (이화여자대학교 임상보건과학대학원) ;
  • 강원구 (대구가톨릭대학교 약학대학) ;
  • 곽혜선 (이화여자대학교 약학대학)
  • Kim, Eun-Young (Graduate School of Clinical Health Sciences, Ewha Womans University) ;
  • Kang, Won-Ku (College of Pharmacy, Catholic University of Daegu) ;
  • Gwak, Hye-Sun (College of Pharmacy, Ewha Womans University)
  • 발행 : 2008.06.30

초록

This study aimed to compare a microparticle enzyme immunoassay (MEIA) with a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for the measurement of tacrolimus concentrations in adult liver transplant recipients, to investigate how the assay choice influenced the population pharmacokinetics of tacrolimus and to identify patient characteristics that affected pharmacokinetic parameters in each assay. Tacrolimus concentrations from 29 liver (n=52 paired-samples) transplant recipients measured by both MEIA and LC/MS/MS were used to evaluate the performance of these methods in the clinical setting. Tacrolimus pharmacokinetics was studied independently using MEIA and LC/MS/MS data in 70 adult patients using a population approach performed with NONMEM. Patient characteristics which influenced pharmacokinetic parameters in each assay were compared. The relation between LC/MS/MS and MEIA measurements was best described by the regression equation MEIA=1.465*LC/MS/MS-1.336 (r=0.91). Multiple linear regression analysis showed significant inverse relationships between assay difference and hematocrit (Hct) (p<0.025) in liver graft recipients. In MEIA, the population estimate of tacrolimus CL/F and apparent volume of distribution (Vd/F) were found to be 10.1 L/h and 226 L, and in LC/MS/MS, 13 L/h and 305 L respectively. Neither patient's age, weight, gender, grafted hepatic weight, albumin concentration, nor markers of liver function influenced tacrolimus CL/F The final model of CL/F was found to be 10.1+(Hct/Hct mean)$^{12.0}$ in MEIA and 13+(1+Hct/578) in LC/MS/MS indicating that CL/F was influenced by hematocrit.

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