Jan Handrick Beumer

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. ncbi request reprint Evaluation of human plasma protein binding of trabectedin (Yondelis, ET-743)
    Jan Handrick Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Curr Clin Pharmacol 4:38-42. 2009
  2. pmc Role of PARP inhibitors in cancer biology and therapy
    D Davar
    Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Curr Med Chem 19:3907-21. 2012
  3. pmc Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Room G27D, 5117 Centre Avenue, Pittsburgh, PA 5213 1863, USA
    Cancer Chemother Pharmacol 67:421-30. 2011
  4. doi request reprint Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    Invest New Drugs 28:145-55. 2010
  5. doi request reprint Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Room G 27d, Hillman Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213 1863, USA
    Clin Cancer Res 14:3529-35. 2008
  6. pmc Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Chemother Pharmacol 62:457-64. 2008
  7. ncbi request reprint Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU)
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA
    Cancer Chemother Pharmacol 62:363-8. 2008
  8. pmc Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Invest New Drugs 25:327-34. 2007
  9. ncbi request reprint Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213 1863, USA
    Clin Cancer Res 12:7483-91. 2006
  10. ncbi request reprint A mass balance and disposition study of the DNA methyltransferase inhibitor zebularine (NSC 309132) and three of its metabolites in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
    Clin Cancer Res 12:5826-33. 2006

Detail Information

Publications18

  1. ncbi request reprint Evaluation of human plasma protein binding of trabectedin (Yondelis, ET-743)
    Jan Handrick Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Curr Clin Pharmacol 4:38-42. 2009
    ..We can conclude that the studied co-medications are unlikely to have clinically relevant effects on trabectedin binding to plasma proteins at therapeutic concentrations...
  2. pmc Role of PARP inhibitors in cancer biology and therapy
    D Davar
    Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Curr Med Chem 19:3907-21. 2012
    ..In this review article, we briefly review the mechanisms of DNA repair and pre-clinical development of PARP inhibitors before discussing the clinical development of the various PARP inhibitors in depth...
  3. pmc Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Room G27D, 5117 Centre Avenue, Pittsburgh, PA 5213 1863, USA
    Cancer Chemother Pharmacol 67:421-30. 2011
    ..Therefore, we characterized THU pharmacokinetics after the administration to mice of the more lipophilic pro-drug triacetyl-THU (taTHU)...
  4. doi request reprint Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    Invest New Drugs 28:145-55. 2010
    ..Although hepatic trabectedin concentrations were not increased when P-gp was absent, mdr1a/1b(-/-) mice experienced more severe liver toxicity. P-gp plays a role in the in vivo disposition and toxicology of trabectedin...
  5. doi request reprint Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Room G 27d, Hillman Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213 1863, USA
    Clin Cancer Res 14:3529-35. 2008
    ..3,4,5,6-Tetrahydrouridine (THU) is a potent CD inhibitor with a 20% oral bioavailability. We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC...
  6. pmc Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Chemother Pharmacol 62:457-64. 2008
    ..This suggests the feasibility of using THU to decrease elimination and first-pass metabolism of cytidine analogues by CD. THU pharmacokinetics are now being evaluated in humans...
  7. ncbi request reprint Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU)
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA
    Cancer Chemother Pharmacol 62:363-8. 2008
    ..We assessed plasma concentrations of FdCyd and metabolites in patients receiving FdCyd and THU...
  8. pmc Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Invest New Drugs 25:327-34. 2007
    ..Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities...
  9. ncbi request reprint Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213 1863, USA
    Clin Cancer Res 12:7483-91. 2006
    ..However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice...
  10. ncbi request reprint A mass balance and disposition study of the DNA methyltransferase inhibitor zebularine (NSC 309132) and three of its metabolites in mice
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
    Clin Cancer Res 12:5826-33. 2006
    ..To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment of cancer...
  11. ncbi request reprint Metabolism of trabectedin (ET-743, Yondelis) in patients with advanced cancer
    Jan H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066, Amsterdam, and Department of Biomedical Analysis, Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands
    Cancer Chemother Pharmacol 59:825-37. 2007
    ..Despite extensive pharmacokinetic studies, the human disposition and metabolism of trabectedin remain largely unknown. We aimed to determine the metabolic profile of trabectedin and to identify its metabolites in humans...
  12. ncbi request reprint Disposition of imatinib and its metabolite CGP74588 in a patient with chronic myelogenous leukemia and short-bowel syndrome
    Jan H Beumer
    Division of Hematology Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
    Pharmacotherapy 26:903-7. 2006
    ..These data indicate the importance of considering gastrointestinal anatomic abnormalities or disease states when oral imatinib is dosed...
  13. ncbi request reprint Mass balance studies, with a focus on anticancer drugs
    Jan H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg, Amsterdam, The Netherlands
    Clin Pharmacokinet 45:33-58. 2006
    ..Metabolic profiling supplements existing knowledge of metabolism. We illustrate the important aspects of a mass balance study with literature on anticancer drugs. This review could serve as guidance for future mass balance studies...
  14. ncbi request reprint Quantitative determination of zebularine (NSC 309132), a DNA methyltransferase inhibitor, and three metabolites in murine plasma by high-performance liquid chromatography coupled with on-line radioactivity detection
    Jan H Beumer
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 831:147-55. 2006
    ..5-50 microg/mL for uridine, 1.0-10 microg/mL for uracil and 0.5-5.0 microg/mL for dihydrouracil. This assay is being used to quantitate zebularine and its metabolites in ongoing pharmacokinetic studies of zebularine...
  15. ncbi request reprint Trabectedin (Yondelis, formerly ET-743), a mass balance study in patients with advanced cancer
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands
    Invest New Drugs 23:429-36. 2005
    ..4% (3-h administration schedule). The excretion of unchanged trabectedin is very low both in faeces and in urine (< 1% of dose). In conclusion, trabectedin is extensively metabolised and principally excreted in the faeces...
  16. ncbi request reprint Human metabolism of [(14)C]indisulam following i.v. infusion in cancer patients
    Jan Hendrik Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Invest New Drugs 23:317-30. 2005
    ..The clinical relevance of the observed indisulam metabolites needs further investigation...
  17. ncbi request reprint Hepatotoxicity and metabolism of trabectedin: a literature review
    J H Beumer
    Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    Pharmacol Res 51:391-8. 2005
    ..Monitoring of plasma levels of liver enzymes ensures safe use of trabectedin in the clinic. Future investigations must be aimed at elucidating the mechanism of trabectedin hepatotoxicity...
  18. ncbi request reprint Trabectedin (ET-743, Yondelis) is a substrate for P-glycoprotein, but only high expression of P-glycoprotein confers the multidrug resistance phenotype
    Jan Hendrik Beumer
    Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
    Invest New Drugs 25:1-7. 2007
    ....