SA Veltkamp

Publications (5)0 Total impact

• Article: In vitro toxicity of gemcitabine and its metabolite 2 ' 2 '-difluorodeoxyuridine in human cancer cells

  SA Veltkamp, F.H.G. Ong, M.J. Bolijn, I. Garcia-Ribas, J.H. Beijnen, J.H.M. Schellens
• Article: A phase I safety and pharmacologic study of a twice weekly dosing regimen of the oral taxane BMS-275133

  L.E. Broker, SA Veltkamp, E.I. Heath, BC Kuenen, H Gall, L. Astier, S. Parker, L. Kayitalire, P.M. Lorusso, J.H.M. Schellens, G Giaccone
• Article: Severe pulmonary toxicity in patients with leiomyosarcoma after treatment with gemcitabine and docetaxel

  SA Veltkamp, J.M. Meerum Terwogt, M.M. van den Heuvel, H.H. van Boven, J.H.M. Schellens, S Rodenhuis
• Article: Quantitative analysis of gemcitabine triphosphate in human peripheral blood mononuclear cells using weak anion-exchange liquid chromatography coupled with tandem mass spectrometry.

  SA Veltkamp, M.J.X. Hillebrand, H. Rosing, R.S. Jansen, ER Wickremsinhe, EJ Perkins, J.H.M. Schellens, J.H. Beijnen
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  ABSTRACT: Gemcitabine triphosphate (dFdCTP) is a highly active metabolite of gemcitabine. It is formed intra-cellularly via the phosphorylation of gemcitabine by deoxycytidine kinase. The monitoring of dFdCTP in human peripheral blood mononuclear cells (PBMCs), in addition to plasma concentrations of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine, is considered very useful in determining pharmacokinetic-pharmacodynamic relationships.We describe a novel sensitive assay for the quantification of dFdCTP in human PBMCs. The method is based on weak anion-exchange liquid chromatography and detection with tandem mass spectrometry (LC-MS/MS). The assay has been validated from 1 ng/ml (lower limit of quantification, LLOQ) to 25 ng/ml (upper limit of quantification, ULOQ) using 180 microl aliquots of PBMC extracts containing approximately 0.648 mg protein or 3.8 x 10(6) lysed PBMCs. The LLOQ is equivalent to 94 fmol/10(6) cells (1 ng/ml = 0.18 ng/180 microl or 0.18 ng/0.648 mg protein = 0.047 ng/10(6) cells or 94 fmol/10(6) cells). This highly sensitive assay is capable of quantifying about 200-fold lower concentrations of dFdCTP in human PBMCs than currently available methods. Copyright (c) 2006 John Wiley & Sons, Ltd.
• Article: A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.

  SA Veltkamp, B Thijssen, JS Garrigue, G Lambert, F Lallemand, F Binlich, A.D.R. Huitema, B. Nuijen, A Nol, J.H. Beijnen, J.H.M. Schellens
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  ABSTRACT: To explore the parmacokinetics, safety and tolerability of paclitaxel after oral administration of SMEOF#3, a novel Self-Microemulsifying Oily Formulation, in combination with cyclosporin A (CsA) in patients with advanced cancer. Seven patients were enrolled and randomly assigned to receive oral paclitaxel (SMEOF#3) 160 mg+CsA 700 mg on day 1, followed by oral paclitaxel (Taxol) 160 mg+CsA 700 mg on day 8 (group I) or vice versa (group II). Patients received paclitaxel (Taxol) 160 mg as 3-h infusion on day 15. The median (range) area under the plasma concentration-time curve of paclitaxel was 2.06 (1.15-3.47) microg h ml(-1) and 1.97 (0.58-3.22) microg h ml(-1) after oral administration of SMEOF#3 and Taxol, respectively, and 4.69 (3.90-6.09) microg h ml(-1) after intravenous Taxol. Oral SMEOF#3 resulted in a lower median T(max) of 2.0 (0.5-2.0) h than orally applied Taxol (T(max)=4.0 (0.8-6.1) h, P=0.02). The median apparent bioavailability of paclitaxel was 40 (19-83)% and 55 (9-70)% for the oral SMEOF#3 and oral Taxol formulation, respectively. Oral paclitaxel administered as SMEOF#3 or Taxol was safe and well tolerated by the patients. Remarkably, the SMEOF#3 formulation resulted in a significantly lower T(max) than orally applied Taxol, probably due to the excipients in the SMEOF#3 formulation resulting in a higher absorption rate of paclitaxel.