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Lewis Sheiner


2020
Ljubljana, Slovenia



2019
Stockholm, Sweden

2018
Montreux, Switzerland

2017
Budapest, Hungary

2016
Lisboa, Portugal

2015
Hersonissos, Crete, Greece

2014
Alicante, Spain

2013
Glasgow, Scotland

2012
Venice, Italy

2011
Athens, Greece

2010
Berlin, Germany

2009
St. Petersburg, Russia

2008
Marseille, France

2007
KÝbenhavn, Denmark

2006
Brugge/Bruges, Belgium

2005
Pamplona, Spain

2004
Uppsala, Sweden

2003
Verona, Italy

2002
Paris, France

2001
Basel, Switzerland

2000
Salamanca, Spain

1999
Saintes, France

1998
Wuppertal, Germany

1997
Glasgow, Scotland

1996
Sandwich, UK

1995
Frankfurt, Germany

1994
Greenford, UK

1993
Paris, France

1992
Basel, Switzerland



Printable version

PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
ISSN 1871-6032

Reference:
PAGE 27 (2018) Abstr 8791 [www.page-meeting.org/?abstract=8791]


Poster: Drug/Disease modelling - Paediatrics


II-77 Catherine Sherwin Tacrolimus population pharmacokinetics in paediatric kidney transplant patients

Shaun S Kumar, Xiaoxi Liu, Silvia Martinez, Jahidur Rashid, Kathleen Job, Alfred Balch, Joseph Rower, Joseph Sherbotie, Catherine M Sherwin

Dept. of Pediatrics, University of Utah, SLC, Utah, USA

Objectives: 1. To describe the pharmacokinetics (PK) of tacrolimus in paediatric kidney transplant recipients. 2. To determine the relationship between measures of tacrolimus exposure and renal function. 3. To determine if there were any differences in either the PK or pharmacodynamics (PD) of tacrolimus in brand versus generic formulations.

Methods: Data from 1999-2014 were extracted from the electronic medical records from Intermountain Healthcare network. Data were available on 95 paediatric patients with kidney transplant taking oral tacrolimus. Reliable data was available in 77 patients. Using the individual predicted PK parameters from the population model several exposure metrics were derived for each dosing interval including; Cmin, Cmax and partial AUCs (2, 4, 6, 8, 10, 12h). We investigated the relationship between tacrolimus exposure and creatinine clearance in the first 30 days post-transplantation, using a simple slope-intercept model as well as an Emax model.

Results: A total of 598 concentrations of tacrolimus were available for analysis. A one-compartment model described the final PK model, the significant covariates on clearance were haematocrit, body weight and post-transplant day. A total of 43 patients had data in the first 30 days post-transplant with a total of 470 creatinine concentrations available. The model that best described the relationship between tacrolimus exposure and creatinine clearance was an Emax model using a partial AUC of 4 hours. The significant covariates of this analysis were age, albumin, and formulation of the ED50 equivalent partial AUC 4h. The generic formulation (Sandoz) had a 35% increase partial AUC50 4h compared to the brand formulation.

Conclusions: In the present work we developed a population PK model for tacrolimus in pediatric kidney transplant recipients the significant covariates have been previously identified [1]. We also determined an exposure-response relationship between tacrolimus and creatinine clearance. This relationship was influenced by patients age and albumin concentrations. Furthermore, we show that there is a difference in the pharmacodynamic effects of tacrolimus when comparing the brand formulation to the generic.



References:
[1] Brooks et al. Population pharmacokinetic modelling and Bayesian estimation of tacrolimus exposure: Is this clincally useful for dosage prediction yet? Clin Pharmacokinet. 2016 May;55:1295-1335.