Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.
Purposes: Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 69; no. 8; pp. 1533 - 1543 |
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| Autores principales: | , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104194213&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104194213 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Aug2013 vid: 69 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104194213 89025430 10.1007/s00228-013-1501-0 NLM23588560 104194213 ppf: 1533 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation. aug: au: Guy-Viterbo, V. Scohy, A. Verbeeck, R. Reding, R. Wallemacq, P. Musuamba, Flora affil: Louvain Center for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels Belgium sug: subj: Antibiotics, Macrolide Pharmacokinetics Liver Transplantation In Infancy and Childhood Drug Monitoring Human Child Models, Theoretical Retrospective Design Infant Child, Preschool Descriptive Statistics Data Analysis Software Confidence Intervals Goodness of Fit Chi Square Test Child: 6-12 years Infant: 1-23 months Child, Preschool: 2-5 years ab: Purposes: Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation. Methods: Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics. Results: The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution. Conclusions: We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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