Alfred H Schinkel

Summary

Affiliation: The Netherlands Cancer Institute
Country: The Netherlands

Publications

  1. doi request reprint OATP1A/1B transporters affect irinotecan and SN-38 pharmacokinetics and carboxylesterase expression in knockout and humanized transgenic mice
    Dilek Iusuf
    Corresponding Author Alfred H Schinkel, Division of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cancer Ther 13:492-503. 2014
  2. pmc Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse
    Wolfgang Kummer
    Institute for Anatomy and Cell Biology, Justus Liebig University, 35385 Giessen, Germany
    Respir Res 7:65. 2006
  3. pmc Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell Biol 27:1247-53. 2007
  4. ncbi request reprint Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview
    Alfred H Schinkel
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Adv Drug Deliv Rev 55:3-29. 2003
  5. ncbi request reprint Polymorphisms affecting function of the human organic cation transporter hOCT1 (SLC22A1): what are the consequences?
    Alfred H Schinkel
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Pharmacogenetics 12:589-90. 2002
  6. doi request reprint Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1)
    Evita van de Steeg
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 37:277-81. 2009
  7. doi request reprint Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo
    Maria L H Vlaming
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cancer Ther 8:3350-9. 2009
  8. doi request reprint Functionally overlapping roles of Abcg2 (Bcrp1) and Abcc2 (Mrp2) in the elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate in vivo
    Maria L H Vlaming
    Divisions of Molecular Biology, The Netherlands Cancer Institute, The Netherlands
    Clin Cancer Res 15:3084-93. 2009
  9. ncbi request reprint Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Carcinogenesis 27:123-30. 2006
  10. ncbi request reprint The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in pat
    Pauline Breedveld
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Cancer Res 65:2577-82. 2005

Collaborators

Detail Information

Publications88

  1. doi request reprint OATP1A/1B transporters affect irinotecan and SN-38 pharmacokinetics and carboxylesterase expression in knockout and humanized transgenic mice
    Dilek Iusuf
    Corresponding Author Alfred H Schinkel, Division of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cancer Ther 13:492-503. 2014
    ..Oatp1a/1b-null mice have increased expression and activity of Ces1 enzymes, whereas humanized mice provide a rescue of this phenotype...
  2. pmc Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse
    Wolfgang Kummer
    Institute for Anatomy and Cell Biology, Justus Liebig University, 35385 Giessen, Germany
    Respir Res 7:65. 2006
    ..Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs...
  3. pmc Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell Biol 27:1247-53. 2007
    ..This study establishes the principle that an ABC transporter can transport a vitamin into milk and raises the possibility that other vitamins and nutrients are likewise secreted into milk by ABC transporters...
  4. ncbi request reprint Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview
    Alfred H Schinkel
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Adv Drug Deliv Rev 55:3-29. 2003
    ..We aim to provide an overview of properties of the mammalian ABC transporters known to mediate significant transport of clinically relevant drugs...
  5. ncbi request reprint Polymorphisms affecting function of the human organic cation transporter hOCT1 (SLC22A1): what are the consequences?
    Alfred H Schinkel
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Pharmacogenetics 12:589-90. 2002
  6. doi request reprint Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1)
    Evita van de Steeg
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 37:277-81. 2009
    ..SLCO1B1 transgenic mice could be a useful tool in studying the in vivo role of human OATP1B1 in drug pharmacokinetics...
  7. doi request reprint Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo
    Maria L H Vlaming
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cancer Ther 8:3350-9. 2009
    ..Nevertheless, cotreatment with possible inhibitors of ABCC2, ABCC3, and ABCG2 should be done with utmost caution when treating patients with methotrexate...
  8. doi request reprint Functionally overlapping roles of Abcg2 (Bcrp1) and Abcc2 (Mrp2) in the elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate in vivo
    Maria L H Vlaming
    Divisions of Molecular Biology, The Netherlands Cancer Institute, The Netherlands
    Clin Cancer Res 15:3084-93. 2009
    ..We investigated the possibly overlapping roles of Abcg2 and Abcc2 in the elimination of the anticancer drug methotrexate (MTX) and its toxic metabolite 7-hydroxymethotrexate (7OH-MTX)...
  9. ncbi request reprint Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Carcinogenesis 27:123-30. 2006
    ..Paradoxically, Bcrp1/BCRP appears to have both protective and adverse roles with respect to exposure to dietary carcinogens...
  10. ncbi request reprint The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in pat
    Pauline Breedveld
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Cancer Res 65:2577-82. 2005
    ..o. imatinib increased 5.2-fold when pantoprazole was co-administered in wild-type mice. Our results suggest that co-administration of BCRP and P-gp inhibitors may improve delivery of imatinib to malignant gliomas...
  11. doi request reprint Inhibition and stimulation of intestinal and hepatic CYP3A activity: studies in humanized CYP3A4 transgenic mice using triazolam
    Robert A B van Waterschoot
    Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 37:2305-13. 2009
    ..The data clarify that for drugs that are not P-glycoprotein substrates, intestinal metabolism also can be more important than hepatic metabolism after oral administration...
  12. doi request reprint Absence of both cytochrome P450 3A and P-glycoprotein dramatically increases docetaxel oral bioavailability and risk of intestinal toxicity
    Robert A B van Waterschoot
    Divisions of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Cancer Res 69:8996-9002. 2009
    ..Simultaneous inhibition of CYP3A/P-gp might thus be a highly effective strategy to improve oral drug bioavailability but with serious risks when applied to drugs with narrow therapeutic windows...
  13. ncbi request reprint Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions
    Pauline Breedveld
    Divisions of Experimental Therapy, Molecular Biology, Clinical Chemistry, and Medical Oncology, The Netherlands Cancer Institute, Amsterdam
    Cancer Res 64:5804-11. 2004
    ..v. MTX in wild-type mice. The conclusion is as follows: benzimidazoles differentially affect transport of MTX mediated by BCRP and MRP2. Competition for BCRP may explain the clinical interaction between MTX and benzimidazoles...
  14. doi request reprint Brain accumulation of sunitinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration
    Seng Chuan Tang
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Int J Cancer 130:223-33. 2012
    ..Complete inhibition of both transporters, leading to markedly increased brain accumulation of sunitinib, is feasible and safe with a clinically realistic oral elacridar/sunitinib coadministration...
  15. doi request reprint Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation
    Jurjen S Lagas
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cancer Ther 9:319-26. 2010
    ....
  16. doi request reprint Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its genotoxic metabolites
    Maria L H Vlaming
    Divisions of Molecular Oncology M L H V, E v d S, A V E, E W, A H S and Clinical Pharmacology J H M S, The Netherlands Cancer Institute, Amsterdam, The Netherlands Division of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands S F T, H R, J H B Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands L B, T F A d G and Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands J H M S, J H B
    Mol Pharmacol 85:520-30. 2014
    ..We conclude that Bcrp1, Mdr1a/b, Mrp2, and Mrp3 significantly affect tissue disposition and biliary and fecal elimination of PhIP and its carcinogenic metabolites and may affect PhIP-induced carcinogenesis as a result. ..
  17. doi request reprint P-glycoprotein and cytochrome P450 3A act together in restricting the oral bioavailability of paclitaxel
    Jeroen J M A Hendrikx
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands Division of Molecular Oncology, The Netherlands
    Int J Cancer 132:2439-47. 2013
    ..Furthermore, CYP3A4-humanized mice allow improved understanding of CYP3A4-mediated paclitaxel metabolism in humans...
  18. ncbi request reprint The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk
    Johan W Jonker
    The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam, The Netherlands
    Nat Med 11:127-9. 2005
    ....
  19. pmc Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Clin Invest 117:3583-92. 2007
    ..The genetic models used in this study provide powerful tools to further study CYP3A-mediated xenobiotic metabolism, as well as interactions between CYP3A and other detoxification systems...
  20. pmc P-glycoprotein limits oral availability, brain penetration, and toxicity of an anionic drug, the antibiotic salinomycin
    Jurjen S Lagas
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands
    Antimicrob Agents Chemother 52:1034-9. 2008
    ..Individuals with reduced or absent P-gp activity could therefore be more susceptible to salinomycin toxicity...
  21. ncbi request reprint In vitro transport of gimatecan (7-t-butoxyiminomethylcamptothecin) by breast cancer resistance protein, P-glycoprotein, and multidrug resistance protein 2
    Serena Marchetti
    Department of Experimental Therapy and Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mol Cancer Ther 6:3307-13. 2007
    ..Implications of BCRP expression in the gut for the oral development of gimatecan and the interaction between gimatecan and other BCRP substrate drugs and/or inhibitors warrant further clinical investigation...
  22. ncbi request reprint Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3) on the in vivo elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate
    Maria L H Vlaming
    Divisions of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 14:8152-60. 2008
    ..We investigated the roles of Abcc2 and Abcc3 in the elimination of the anticancer drug methotrexate (MTX) and its toxic metabolite 7-hydroxymethotrexate (7OH-MTX) in vivo...
  23. ncbi request reprint Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2)
    Gracia Merino
    The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam, The Netherlands
    Drug Metab Dispos 33:614-8. 2005
    ..The use of efficacious BCRP/Bcrp1 inhibitors might increase the extent and duration of systemic exposure to ABZSO and OXF, with possible therapeutically beneficial effects in extra-intestinal infections...
  24. doi request reprint Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib
    Seng Chuan Tang
    Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Pharmacol Exp Ther 346:486-94. 2013
    ..Moreover, retrospective analysis of fetal accumulation of drugs across the placenta in Abcb1a/1b heterozygous knockout pups suggests that these models equally apply to the maternal-fetal barrier. ..
  25. doi request reprint Murine Oatp1a/1b uptake transporters control rosuvastatin systemic exposure without affecting its apparent liver exposure
    Dilek Iusuf
    Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mol Pharmacol 83:919-29. 2013
    ....
  26. doi request reprint Brain accumulation of dasatinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by elacridar treatment
    Jurjen S Lagas
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 15:2344-51. 2009
    ..For dasatinib, an inhibitor of SCR/BCR-ABL kinases, in vivo interactions with P-gp and ABCG2 are not fully established yet...
  27. doi request reprint High impact of Oatp1a/1b transporters on in vivo disposition of the hydrophobic anticancer drug paclitaxel
    Evita van de Steeg
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 17:294-301. 2011
    ..We investigated the role of Oatp1a/1b transporters in the pharmacokinetics of PTX in vivo, as well as their impact at different dose levels of PTX and methotrexate (MTX)...
  28. ncbi request reprint Contribution of the ABC transporters Bcrp1 and Mdr1a/1b to the side population phenotype in mammary gland and bone marrow of mice
    Johan W Jonker
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Stem Cells 23:1059-65. 2005
    ..Interestingly, bone marrow of Mdr1a/1b-/- mice frequently displayed an elevated SP, which was reversible by the Bcrp1 inhibitor Ko143, suggesting that Bcrp1 can compensate for the loss of Mdr1a/1b in bone marrow...
  29. ncbi request reprint The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Res 63:6447-52. 2003
    ..Intra- or interindividual differences in BCRP activity in humans may thus also affect the exposure to PhIP and related food carcinogens, with possible implications for cancer susceptibility...
  30. pmc Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver
    Evita van de Steeg
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Clin Invest 122:519-28. 2012
    ..Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks...
  31. doi request reprint Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors
    Roos L Oostendorp
    The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 37:917-23. 2009
    ....
  32. ncbi request reprint Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX
    Johan W Jonker
    Div of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Am J Physiol Cell Physiol 292:C2204-12. 2007
    ..This mechanism may allow cells to prevent or reduce cytotoxicity of PPIX under excess conditions, without spillage under physiological conditions where PPIX is needed...
  33. ncbi request reprint Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein
    John D Allen
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Cancer Res 63:1339-44. 2003
    ..It may thus be worthwhile to test inhibition of P-gp in humans to improve the oral availability of etoposide...
  34. doi request reprint Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2
    Dirk R de Waart
    Liver Center, Academic Medical Center, Meibergdreef 69 71, Amsterdam, The Netherlands
    Drug Metab Dispos 37:1698-702. 2009
    ..5%) compared with that in wild-type mice. These data demonstrate that the enterohepatic circulation of Ez-gluc strongly depends on the joint function of Abcc3, Abcc2, and Abcg2...
  35. doi request reprint Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2)
    Christian Zimmermann
    Division of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 36:631-40. 2008
    ..These differences should be taken into account when results obtained in mice are extrapolated to humans...
  36. ncbi request reprint Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir
    Maarten T Huisman
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Pharmacol Exp Ther 304:596-602. 2003
    ..Clinical attempts to efficiently inhibit P-glycoprotein function for improved HPI disposition may therefore be feasible, but they should be performed without ritonavir and monitored carefully for unexpected toxicities...
  37. doi request reprint Physiological and pharmacological roles of ABCG2 (BCRP): recent findings in Abcg2 knockout mice
    Maria L H Vlaming
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Adv Drug Deliv Rev 61:14-25. 2009
    ..However, the physiological significance of these processes has been difficult to establish, indicating that there is still a lot to learn about this intriguing protein...
  38. ncbi request reprint Influence of human OATP1B1, OATP1B3, and OATP1A2 on the pharmacokinetics of methotrexate and paclitaxel in humanized transgenic mice
    Evita van de Steeg
    Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 19:821-32. 2013
    ....
  39. doi request reprint Double-transduced MDCKII cells to study human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) interplay in drug transport across the blood-brain barrier
    Birk Poller
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mol Pharm 8:571-82. 2011
    ..MDCKII-ABCB1/ABCG2 cells thus present a useful in vitro model to study the interplay of ABCB1 and ABCG2...
  40. doi request reprint P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict brain accumulation of the active sunitinib metabolite N-desethyl sunitinib
    Seng Chuan Tang
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Pharmacol Exp Ther 341:164-73. 2012
    ..The effect of elacridar treatment in improving brain accumulation of N-desethyl sunitinib in wild-type mice was limited compared with its effect on sunitinib brain accumulation...
  41. doi request reprint Hepatic clearance of reactive glucuronide metabolites of diclofenac in the mouse is dependent on multiple ATP-binding cassette efflux transporters
    Jurjen S Lagas
    Division Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Pharmacol 77:687-94. 2010
    ..We believe that the handling of diclofenac acyl glucuronides by ATP binding cassette transporters may be representative for the handling of acyl glucuronide metabolites of many other clinically relevant drugs...
  42. pmc Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs
    Evita van de Steeg
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Clin Invest 120:2942-52. 2010
    ..Slco1a/1b-/- mice will provide excellent tools to study further the role of Oatp1a/1b transporters in physiology and drug disposition...
  43. doi request reprint Intestinal cytochrome P450 3A plays an important role in the regulation of detoxifying systems in the liver
    Robert A B van Waterschoot
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    FASEB J 23:224-31. 2009
    ..This broad biological effect further emphasizes the importance of intestinal CYP3A activity and could have profound implications for the prediction of drug exposure...
  44. doi request reprint P-glycoprotein (P-gp/Abcb1), Abcc2, and Abcc3 determine the pharmacokinetics of etoposide
    Jurjen S Lagas
    Authors Affiliations Divisions of Molecular Biology and Clinical Chemistry, The Netherlands Cancer Institute, and Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands
    Clin Cancer Res 16:130-40. 2010
    ..We aimed to study the impact of P-glycoprotein (P-gp/ABCB1) and the multidrug resistance proteins ABCC2 (MRP2) and ABCC3 (MRP3) on the pharmacokinetics of etoposide...
  45. ncbi request reprint Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver
    Gracia Merino
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam
    Mol Pharmacol 67:1765-71. 2005
    ....
  46. pmc Midazolam metabolism in cytochrome P450 3A knockout mice can be attributed to up-regulated CYP2C enzymes
    Robert A B van Waterschoot
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Pharmacol 73:1029-36. 2008
    ..Such flexible compensatory interplay between functionally related detoxifying systems is probably essential to their biological role in xenobiotic protection...
  47. ncbi request reprint Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar
    Seng Chuan Tang
    Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Int J Cancer 134:1484-94. 2014
    ..This principle might be used to enhance therapeutic efficacy of crizotinib against brain metastases in NSCLC patients...
  48. doi request reprint Differential impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on axitinib brain accumulation and oral plasma pharmacokinetics
    Birk Poller
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Drug Metab Dispos 39:729-35. 2011
    ..These findings illustrate that in vitro transport data for ABCB1 and ABCG2 cannot always be simply extrapolated to the prediction of the relative impact of these transporters on oral availability versus brain penetration...
  49. ncbi request reprint Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C
    John D Allen
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam
    Mol Cancer Ther 1:417-25. 2002
    ..As such, Ko143 and other FTC analogues of this type represent valuable reagents for analysis of drug resistance mechanisms and may be candidates for development as clinical BCRP inhibitors...
  50. doi request reprint Oral availability and brain penetration of the B-RAFV600E inhibitor vemurafenib can be enhanced by the P-GLYCOprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar
    Selvi Durmus
    Division of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Pharm 9:3236-45. 2012
    ..Our data suggest that elacridar coadministration may be considered to improve the therapeutic efficacy of vemurafenib, especially for brain metastases located behind a functional blood-brain barrier...
  51. ncbi request reprint Organic anion-transporting polypeptides 1a/1b control the hepatic uptake of pravastatin in mice
    Dilek Iusuf
    Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mol Pharm 9:2497-504. 2012
    ..Activity-reducing human OATP1B polymorphisms may therefore both reduce pravastatin therapeutic efficacy in the liver and increase systemic toxicity risks, thus compromising its therapeutic index in a two-edged way...
  52. doi request reprint Impact of abcc2 [multidrug resistance-associated protein (MRP) 2], abcc3 (MRP3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate
    Maria L H Vlaming
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Drug Metab Dispos 39:1338-44. 2011
    ..Such conditions may also present risk factors for increased MTX-related toxicity in patients treated with oral MTX...
  53. doi request reprint An integrated pharmacokinetic model for the influence of CYP3A4 expression on the in vivo disposition of lopinavir and its modulation by ritonavir
    Rob ter Heine
    Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands
    J Pharm Sci 100:2508-15. 2011
    ..Hepatic CYP3A4 related systemic clearance was inversely related to ritonavir exposure and not only hepatic but also intestinal CYP3A4 expression contributed to systemic clearance of lopinavir...
  54. ncbi request reprint Multidrug resistance protein 2 is an important determinant of paclitaxel pharmacokinetics
    Jurjen S Lagas
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 12:6125-32. 2006
    ..We found previously that human multidrug resistance protein 2 (MRP2; ABCC2) also transports paclitaxel in vitro, and although we expected that paclitaxel pharmacokinetics would be dominated by P-gp, the effect of Mrp2 was tested in vivo...
  55. ncbi request reprint MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid
    Maarten T Huisman
    Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam, The Netherlands
    Int J Cancer 116:824-9. 2005
    ....
  56. ncbi request reprint Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides
    Koen van de Wetering
    Division of Molecular Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Pharmacol 72:387-94. 2007
    ..Our results show that murine Mrp2 and Mrp3 provide alternative routes for the excretion of a glucuronidated substrate from the liver in vivo...
  57. ncbi request reprint The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin
    Gracia Merino
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam
    Mol Pharmacol 67:1758-64. 2005
    ..We conclude that Bcrp1 is an important determinant for the bioavailability of nitrofurantoin and the main mechanism involved in its hepatobiliary excretion and secretion into the milk...
  58. doi request reprint Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transport by diclofenac and benzbromarone
    Jurjen S Lagas
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 37:129-36. 2009
    ..Moreover, stimulation of MRP2 activity in tumors may lead to increased efflux of chemotherapeutic drugs and thereby drug resistance...
  59. doi request reprint Individual and combined roles of CYP3A, P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) in the pharmacokinetics of docetaxel
    Robert A B van Waterschoot
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Int J Cancer 127:2959-64. 2010
    ..These findings could have important implications for improving the oral bioavailability and reducing the variability in docetaxel exposure...
  60. ncbi request reprint The function of breast cancer resistance protein in epithelial barriers, stem cells and milk secretion of drugs and xenotoxins
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Trends Pharmacol Sci 27:10-6. 2006
    ..In apparent contradiction with the detoxifying role of BCRP in mothers, this contamination of milk exposes suckling infants and dairy consumers to xenotoxins. BCRP thus affects many important aspects of pharmacology and toxicology...
  61. ncbi request reprint Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs
    Maarten T Huisman
    Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    AIDS 16:2295-301. 2002
    ....
  62. ncbi request reprint Midazolam and cyclosporin a metabolism in transgenic mice with liver-specific expression of human CYP3A4
    Antonius E van Herwaarden
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Drug Metab Dispos 33:892-5. 2005
    ..We expect that this CYP3A4 transgenic model will provide a useful tool to study the impact of CYP3A4 on drug levels, especially when combined with other transgenic and knockout strains...
  63. pmc The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria
    Johan W Jonker
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 99:15649-54. 2002
    ....
  64. doi request reprint PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide
    Christian Zimmermann
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Eur J Pharm Sci 36:565-71. 2009
    ..Therefore, the risk for budesonide-mediated drug interactions seems to be low but cannot be ruled out entirely...
  65. ncbi request reprint Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2)
    Noam Zelcer
    Division of Molecular Biology and Center of Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Biol Chem 278:23538-44. 2003
    ..We propose that MRP2 contains two similar but nonidentical ligand binding sites: one site from which substrate is transported and a second site that regulates the affinity of the transport site for the substrate...
  66. doi request reprint A sensitive assay for the quantitative analysis of vinorelbine in mouse and human EDTA plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry
    Carola W N Damen
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 868:102-9. 2008
    ..The lower limit of quantification in mouse plasma is 0.8 ng/mL. This assay is used to support preclinical and clinical pharmacologic studies with vinorelbine...
  67. doi request reprint P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration
    Dilek Iusuf
    The Netherlands Cancer Institute, Division of Molecular Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Pharmacol Exp Ther 337:710-7. 2011
    ..P-gp might thus be relevant for tamoxifen/endoxifen resistance of P-gp-positive breast cancer and tumors positioned behind a functional blood-brain barrier...
  68. doi request reprint How important is intestinal cytochrome P450 3A metabolism?
    Antonius E van Herwaarden
    Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Trends Pharmacol Sci 30:223-7. 2009
    ..We expect that the insights obtained with these mouse models will contribute to the development of better oral drugs and treatment regimens...
  69. doi request reprint Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the power of combination knockout mice
    Jurjen S Lagas
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Mol Interv 9:136-45. 2009
    ..In addition, the characterization of these mice and some physiological aspects of ABC multidrug transporters are addressed...
  70. doi request reprint A sensitive combined assay for the quantification of paclitaxel, docetaxel and ritonavir in human plasma using liquid chromatography coupled with tandem mass spectrometry
    Jeroen J M A Hendrikx
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 879:2984-90. 2011
    ..The described method was successfully applied in clinical studies with oral administration of docetaxel or paclitaxel in combination with ritonavir...
  71. doi request reprint A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: recent insights from knockout and transgenic mice
    Robert A B van Waterschoot
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Pharmacol Rev 63:390-410. 2011
    ..Above all, the recent findings and insights into the interplay between CYP3A and P-glycoprotein may have implications for improving oral drug bioavailability and reducing adverse side effects...
  72. ncbi request reprint Absence of N-linked glycosylation does not affect plasma membrane localization of breast cancer resistance protein (BCRP/ABCG2)
    Karin Mohrmann
    Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands
    Cancer Chemother Pharmacol 56:344-50. 2005
    ..However, BCRP-N557A and the triple mutant were mainly localized intracellularly, probably in the endoplasmic reticulum, suggesting that this mutation disrupted proper routing of BCRP...
  73. pmc Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations
    Johan W Jonker
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Mol Cell Biol 23:7902-8. 2003
    ..This study shows that Oct1 and Oct2 together are essential for renal secretion of (small) organic cations. A deficiency in these proteins may thus result in increased drug sensitivity and toxicity...
  74. ncbi request reprint Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3)
    Johan W Jonker
    The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam, The Netherlands
    J Pharmacol Exp Ther 308:2-9. 2004
    ....
  75. ncbi request reprint A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell lines selected for Doxorubicin resistance
    John D Allen
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Res 62:2294-9. 2002
    ..The same is most likely true of human BCRP, given its profound similarities to mouse Bcrp1...
  76. doi request reprint Involvement of multiple efflux transporters in hepatic disposition of fexofenadine
    Soichiro Matsushima
    Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Mol Pharmacol 73:1474-83. 2008
    ..On the other hand, pharmacokinetics of FEX remained unchanged in Mrp4(-/-) mice. This information provides a novel insight into the transporters important for FEX disposition...
  77. ncbi request reprint Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin
    De Sheng Wang
    Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkuo ku, Tokyo 113 0033, Japan
    J Pharmacol Exp Ther 302:510-5. 2002
    ....
  78. ncbi request reprint Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones
    Tomohiro Ando
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
    Drug Metab Dispos 35:1873-9. 2007
    ..The present study shows that BCRP mediates the biliary excretion of fluoroquinolones and suggests that it is also involved in the tubular secretion of ciprofloxacin and grepafloxacin...
  79. ncbi request reprint Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion
    Gracia Merino
    Department of Physiology, Faculty of Veterinary Medicine, University of Leon, Campus de Vegazana, 24071 Leon, Spain
    Drug Metab Dispos 34:690-5. 2006
    ..We conclude that Bcrp1 is one of the determinants for the bioavailability of fluoroquinolones and their secretion into the milk...
  80. ncbi request reprint Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine
    Petr Pavek
    Department of Pharmacology and Toxicology and Research Center, Charles University in Prague, Faculty of Pharmacy, Hradec, Kralove, The Czech Republic
    J Pharmacol Exp Ther 312:144-52. 2005
    ..The generated BCRP-expressing cell lines thus provide valuable tools to study pharmacological and toxicological interactions mediated by BCRP and to identify new BCRP substrates...
  81. ncbi request reprint Investigation of efflux transport of dehydroepiandrosterone sulfate and mitoxantrone at the mouse blood-brain barrier: a minor role of breast cancer resistance protein
    Young Joo Lee
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, 113 0033, Japan
    J Pharmacol Exp Ther 312:44-52. 2005
    ....
  82. pmc P glycoprotein in human immunodeficiency virus type 1 infection and therapy
    Sanjay U C Sankatsing
    Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands
    Antimicrob Agents Chemother 48:1073-81. 2004
  83. pmc Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels
    Elke Schneider
    UMR 8147, Centre National de la Recherche Scientifique, Faculté de Médecine René Descartes, Paris V, Hopital Necker, 75015 Paris, France
    J Exp Med 202:387-93. 2005
    ..We postulate that pharmacologic modulation of histamine transport might become instrumental in the control of basophil functions during allergic diseases...
  84. ncbi request reprint Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study
    Jacques Fellay
    Division of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland
    Lancet 359:30-6. 2002
    ..This variability could have a genetic basis. We did a pharmacogenetics study to analyse the association between response to antiretroviral treatment and allelic variants of several genes...
  85. ncbi request reprint Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin
    De Sheng Wang
    Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
    Mol Pharmacol 63:844-8. 2003
    ....
  86. ncbi request reprint Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen
    Yasuhisa Adachi
    Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Mol Pharmacol 67:923-8. 2005
    ..Therefore, Bcrp1 has an important role in extruding glucuronide and sulfate conjugates formed in enterocytes into the intestinal lumen, whereas Mrp2 is responsible for the efflux of some glucuronide conjugates...
  87. ncbi request reprint Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2)
    John D Allen
    The Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia
    Mol Cancer Ther 1:427-34. 2002
  88. doi request reprint Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds
    Junichi Enokizono
    Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Drug Metab Dispos 36:995-1002. 2008
    ..These results suggest that BCRP limits the tissue penetration of xenobiotic compounds in the blood-brain and -testis barriers, but its in vivo importance is also modulated by P-glycoprotein activity...