Clinical pharmacology of the tyrosine kinase inhibitors imatinib and sunitinib Erp, P.H. van

Clinical pharmacology of the tyrosine kinase inhibitors imatinib and sunitinib

Erp, P.H. van

Citation

Erp, P. H. van. (2009, December 16). Clinical pharmacology of the tyrosine kinase inhibitors imatinib and sunitinib. Retrieved from

https://hdl.handle.net/1887/14515

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License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

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Nielka van Erp

Clinical Pharmacology

of the Tyrosine Kinase Inhibitors

Imatinib and Sunitinib

The research presented in this thesis was performed at the Department of Clinical Pharmacy and Toxicology of Leiden University Medical Center, The Netherlands.

Publication of this thesis was sponsored by:

AZL Onderzoeks- en Ontwikkelingskrediet (OOK) Apotheek

Koninklijke Nederlandse Maatschappij ter Bevordering der Pharmacie (KNMP)

Cover design and layout by: In Zicht Grafisch Ontwerp, Arnhem, www.promotie-inzicht.nl Printed by: Ipskamp Drukkers, Enschede

ISBN 978-90-9024737-3

© P.H. van Erp 2009

All rights reserved. No parts of this publication may be reproduced, stored in a retrieval system of any nature, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior written permission of the publisher.

Clinical Pharmacology

of the Tyrosine Kinase Inhibitors Imatinib and Sunitinib

Proefschrift

ter verkrijging van

de graad Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. P.F. van der Heijden,

volgens besluit van het College voor Promoties ter verdedigen op woensdag 16 december 2009

klokke 13:45 uur

door

Petronella Hubertha van Erp

in 1977

“Nothing in life is to be feared, it is only to be understood”

Marie Curie Promotor

Prof. Dr. H.-J. Guchelaar

Copromotor Dr. A.J. Gelderblom

Overige leden Prof. Dr. M. Danhof

Prof. Dr. H.M.W. Verheul, Vrije Universiteit, Amsterdam Prof. Dr. J.H. Beijnen, Universiteit Utrecht

Dr. A. Sparreboom, St. Jude Children's Research Hospital, Memphis, USA

1 General introduction 9

2 Clinical pharmacokinetics of tyrosine kinase inhibitors 17

Cancer Treatment Reviews 2009 (in press)

Part 1 Clinical Pharmacology of Imatinib 53

3 Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib 55 Clinical Cancer Research 2007; 13(24):7394-7400

4 Effect of cigarette smoking on pharmacokinetics, safety and efficacy of imatinib: 73 a study based on data of the Soft Tissue and Bone Sarcoma Group of the EORTC

Clinical Cancer Research 2008; 14(24):8308-8313

5 Is rectal administration of imatinib an alternative route for imatinib? 89 Cancer Chemotherapy and Pharmacology 2007; 60(4):623-624

Part 2 Clinical Pharmacology of Sunitinib 95

6 Relationship between CYP3A4 phenotyping and sunitinib exposure in cancer patients 97 7 Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity 111

Journal of Clinical Oncology 2009 (published online ahead of print, August 10, 2009)

8 Clinically irrelevant effect of grapefruit juice on the steady-state sunitinib exposure 131 Submitted

9 Mitotane has a strong inducing effect on CYP3A4 activity 149

Submitted

10 Absorption of cytochrome P450 3A4 inhibiting furanocoumarins from grapefruit 159 juice after oral administration

Submitted

Part 3 Appendix 171

11 General Discussion and Future Perspectives 173

Summary 185

Nederlandse samenvatting 193

Dankwoord 203

List of Publications 205

Curriculum Vitae 207

Contents