Individualized dosing of calcineurin inhibitors in renal transplantation
Press, R.R.
Citation
Press, R. R. (2011, April 13). Individualized dosing of calcineurin inhibitors in renal transplantation. Retrieved from https://hdl.handle.net/1887/16715
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the
University of Leiden
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Individualized Dosing of Calcineurin Inhibitors in
Renal Transplantation
Individualized Dosing of Calcineurin Inhibitors in
Renal Transplantation
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof. mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op woensdag 13 april 2011 klokke 16.15 uur
door
Rogier Raphael Press geboren te Rotterdam
in 1978
promotiecommissie promotores Prof. dr. H-J. Guchelaar
Prof. dr. J.W. de Fijter Prof. dr. M. Danhof copromotor Dr. B.A. Ploeger overige leden Prof. dr. T. van Gelder,
Erasmus Universiteit Rotterdam Prof. dr. C.A.J. Knibbe Dr. F.J. Bemelman, Universiteit van Amsterdam
aan Marion
The research presented in this thesis was performed at the Departments of Clinical Pharmacy &
Toxicology, Nephrology and Clinical Chemistry of the Leiden University Medical Center, Leiden, The Netherlands. Besides, this research was performed in close collaboration with the Pharmacology department of the Leiden/Amsterdam Center for Drug Research and LAP&P Consultants BV, Leiden.
© Rogier Press, 2011. Except: Chapter 2: Reproduced with permission from Current Pharmaceutical design, Press et al., 16(2): pages 176-186 (2010), Bentham Science Publishers Ltd.; Chapter 3: Repro- duced with permission from Therapeutic Drug Monitoring, Press et al. 31(2): pages 187-197 (2009), Wolters Kluwer Health/Lippincott Williams & Wilkins; Chapter 4: Reproduced with kind permission from the European Journal of Clinical Pharmacology, Press et al. 66(6): pages 579-590 (2010), Springer Science + Business Media; Chapter 5: Reproduced from Clinical Chemistry, van Rossum et al. 56(5):
pages 732-735 (2010), AACC.
Niets uit deze uitgave mag worden verveelvoudigd en/of openbaar gemaakt zonder voorafgaande schriftelijke toestemming van de auteur. No part of this thesis may be reproduced in any form with- out written permission from the author.
isbn 978-90-9026037-2
Foto omslag Hannie Joziasse/Buiten-Beeld/HH Vormgeving Sam Gobin, Leiden
Druk Drukkerij Mostert & Van Onderen, Leiden
Financial Support for the publication of this thesis was provided by AZL Onderzoeks- en Ontwikkel- ingskrediet Apotheek, Afdeling Nierziekten LUMC, J.E. Jurriaanse Stichting, Nederlandse Transplan- tatievereniging, Stichting KNMP-fondsen and LAP&P Consultants BV.
List of Abbreviations – 11 1 General Introduction – 13
2 Individualizing Calcineurin Inhibitor Therapy in Renal Transplantation – Current Limitations and Perspectives – 19 3 Explaining Variability in Tacrolimus Pharmacokinetics
to Optimize Early Exposure in Adult Kidney Transplant Recipients – 37
4 Explaining Variability in Ciclosporin Exposure in Adult Kidney Transplant Recipients – 57
5 A call for advanced pharmacokinetic and pharmacodynamic monitoring to guide calcineurin inhibitor dosing in renal transplant recipients – 75
6 Is Calcineurin Activity a Useful Biomarker to Optimize Ciclosporin A Therapy in Renal Transplant Recipients? – 81 7 Identifying Pharmacological Risk Factors for Subclinical
Rejection in Renal Transplant Recipients on Controlled Ciclosporin Exposure – 97
8 Individualized Dosing of Calcineurin Inhibitors in Renal Transplantation –General Discussion and Perspectives – 113 9 Summary – 129
Nederlandse Samenvatting – 135 Curriculum vitae – 141
List of publications – 142 Nawoord – 144
Inhoud
10
11 LIst of AbbrevIAtIons
ABCB ATP-Binding Cassette sub-family B APC Antigen Presenting Cell
AUC Area under the blood concentration-over time curve
CsA Ciclosporin A
CAN Chronic Allograft Nephropathy
CMV Cytomegalovirus
CNI Calcineurin inhibitor
CYP Cytochrome P450
Cyp Cyclophilines
DDPR Daily Dose Prednisolone EBV Epstein Bar Virus ESRD End Stage Renal Disease FKBP FK506-Binding Protein
FPIA Fluorescence Polarization Immunoassay GFR Glomerular Filtration Rate
HLA Human Leukocyte Antigen
IF/TA Interstitial Fibrosis/Tubular Atrophy IIV Inter-individual variability
IOV Inter-occasion variability
LC-MS/MS Liquid Chromatography Tandem Mass Spectrometry MEIA Microparticle Enzyme Immunoassay
MVOF Minimum Value of the Objective Function NFAT Nuclear Factor of Activated T-cells NONMEM Non Linear Mixed Effects Modeling PCR Polymerase Chain Reaction
PD Pharmacodynamics
PK Pharmacokinetics
PPP Protein Phosphatase PXR Pregnane X receptor SCR Subclinical Rejection
SNP Single Nucleotide Polymorphism TDM Therapeutic Drug Monitoring
TRL Tacrolimus
