Population Pharmacokinetic Analysis of Tacrolimus Early After Pediatric Liver Transplantation

被引:5
作者
Musuamba, Flora T. [1 ,2 ]
Guy-Viterbo, Vanessa [1 ]
Reding, Raymond [3 ]
Verbeeck, Roger K. [2 ]
Wallemacq, Pierre [1 ]
机构
[1] Catholic Univ Louvain, Louvain Ctr Toxicol & Appl Pharmacol, B-1200 Brussels, Belgium
[2] Catholic Univ Louvain, Louvain Drug Res Inst, B-1200 Brussels, Belgium
[3] Catholic Univ Louvain, St Luc Univ Hosp, Transplantat Unit, B-1200 Brussels, Belgium
关键词
tacrolimus; population pharmacokinetics; pediatric liver transplantation; modeling; dose individualization; SOLID-ORGAN TRANSPLANTATION; APPARENT CLEARANCE; RECIPIENTS; PREDICTION; PHARMACODYNAMICS; POLYMORPHISMS; THERAPY; MODEL; PARAMETERS; CHILDREN;
D O I
暂无
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: Tacrolimus (TAC) pharmacokinetics (PKs) show considerable unexplained variability, particularly in the early period after transplantation. Therefore, TAC is a good candidate for therapeutic drug monitoring. The main objective of the present work was to propose a robust PK model for TAC in the early period after transplantation, with the final goal to provide practitioners with a tool for dose individualization in pediatric patients. Methods: TAC concentration data were obtained from 82 pediatric liver allograft recipients during the first 2 weeks after transplantation. Previously published models, and a model recently developed by our group for pediatrics early after pediatric liver transplantation, were fitted to the data and their predictive performance compared with the performances of a model developed using the data from 82 pediatric patients. Results: During the data-driven analysis, the PKs of TAC were best described by a 1-compartment model with time-varying first order elimination. Apparent volume of distribution and blood clearance estimates were 283 L and 10 L/h, respectively. The absorption was also considered to be a first order process, with a first order rate fixed to 4.45 hours. Parameters were estimated with good precision and accuracy. Although hematocrit levels, time after transplantation, liver weight, and body weight influenced the clearance, body weight was the only covariate retained on volume of central and peripheral compartments. Two of the 5 previous models showed acceptable predictive performances using the observed data. Conclusions: Time after transplantation, body weight, and hematocrit levels were shown to influence TAC PK in the early pediatric post-liver transplantation period and should be considered, besides therapeutic drug monitoring, by clinicians for the TAC posology prescription and adaptation.
引用
收藏
页码:54 / 61
页数:8
相关论文
共 32 条
[11]   PHARMACOKINETICS OF TACROLIMUS IN LIVER-TRANSPLANT PATIENTS [J].
JUSKO, WJ ;
PIEKOSZEWSKI, W ;
KLINTMALM, GB ;
SHAEFER, MS ;
HEBERT, MF ;
PIERGIES, AA ;
LEE, CC ;
SCHECHTER, P ;
MEKKI, QA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 57 (03) :281-290
[12]   Safety and efficacy of tacrolimus in pediatric liver recipients [J].
Kelly, Deirdre .
PEDIATRIC TRANSPLANTATION, 2011, 15 (01) :19-24
[13]   Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients [J].
Li, D. ;
Lu, W. ;
Zhu, J.-Y. ;
Gao, J. ;
Lou, Y.-Q. ;
Zhang, G.-L. .
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, 2007, 32 (05) :505-515
[14]   Calcineurin Inhibitor Nephrotoxicity [J].
Naesens, Maarten ;
Kuypers, Dirk R. J. ;
Sarwal, Minnie .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 4 (02) :481-508
[15]   Tacrolimus pharmacokinetics in the early post-liver transplantation period and clinical applicability via Bayesian prediction [J].
Oteo, Itziar ;
Lukas, John C. ;
Leal, Nerea ;
Suarez, Elena ;
Valdivieso, Andres ;
Gastaca, Mikel ;
Ortiz de Urbina, Jorge ;
Calvo, Rosario .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 69 (01) :65-74
[16]  
Rodriguez-Peralvarez M, 2012, Am J Transplant, V12, P2797
[17]   Population pharmacokinetics of tacrolimus in whole blood and plasma in Asian liver transplant patients [J].
Sam, WJ ;
Tham, LS ;
Holmes, MJ ;
Aw, M ;
Quak, SH ;
Lee, KH ;
Lim, SG ;
Prabhakaran, K ;
Chan, SY ;
Ho, PC .
CLINICAL PHARMACOKINETICS, 2006, 45 (01) :59-75
[18]   Population pharmacokinetics of tacrolimus in Asian paediatric liver transplant patients [J].
Sam, WJ ;
Aw, M ;
Quak, SH ;
Lim, SM ;
Charles, BG ;
Chan, SY ;
Ho, PC .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 50 (06) :531-541
[19]   Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy [J].
Sánchez, MJG ;
Manzanares, C ;
Santos-Buelga, D ;
Blázquez, A ;
Manzanares, J ;
Urruzuno, P ;
Medina, E .
CLINICAL PHARMACOKINETICS, 2001, 40 (01) :63-71
[20]   New Equations to Estimate GFR in Children with CKD [J].
Schwartz, George J. ;
Munoz, Alvaro ;
Schneider, Michael F. ;
Mak, Robert H. ;
Kaskel, Frederick ;
Warady, Bradley A. ;
Furth, Susan L. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (03) :629-637