Stephanie van Hoppe

TA B L E O F CON T E N T S Preface 7 Chapter 1 Introduction 9 Chapter 2 Breast cancer resistance protein (BCRP/ABCG2) and 21 P-glycoprotein (P-gp/ABCB1) transport afatinib and restrict its oral availability and brain accumulation Chapter 3 Brain accumulation of osimertinib and its active metabolite 43 AZ5104 is restricted by ABCB1 (P-glycoprotein) and ABCG2 (Breast Cancer Resistance Protein) Chapter 4 P-glycoprotein (MDR1/ABCB1) restricts brain penetration 69 of the Bruton’s tyrosine kinase inhibitor ibrutinib while Cytochrome P450-3A (CYP3A) limits its oral bioavailability Chapter 5 Brain accumulation of ponatinib and its active metabolite 99 N-desmethyl ponatinib is limited by P-glycoprotein (P-GP/ ABCB1) and breast cancer resistance protein (BCRP/ABCG2) Chapter 6 The impact of Organic Anion-Transporting Polypeptides 125 (OATPs) on disposition and toxicity of antitumor drugs; insights from knockout and humanized mice Chapter 7 Conclusions and future perspectives 167 Chapter 8 Summary 173 Appendices Nederlandse samenvatting 181 Résumé en français 183 Curriculum vitae 185 List of publications 186 Acknowledgements 188