title: [Metastasized renal cell carcinoma. Measurement of plasma levels of the tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib].
abstract: BACKGROUND
  Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS).
  
  
  METHODS
  A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry.
  
  
  RESULTS
  The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals.
  
  
  CONCLUSIONS
  Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.
authors.affiliation: Klinik für Urologie und Kinderurologie, Universitätsklinikum Gießen und Marburg, Standort Marburg, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland, keilc@med.uni-marburg.de.
authors.forename: C
authors.initials: C
authors.lastname: Keil
authors.forename: L
authors.initials: L
authors.lastname: Götze
authors.forename: P
authors.initials: P
authors.lastname: Olbert
authors.forename: R
authors.initials: R
authors.lastname: Hofmann
authors.forename: W A
authors.initials: WA
authors.lastname: Nockher
authors.forename: A
authors.initials: A
authors.lastname: Hegele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy / Q000556:secondary*; D016903:Drug Monitoring / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000097:blood* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000097:blood* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000097:blood* / Q000627:therapeutic use; D011758:Pyrroles / Q000097:blood* / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D013449:Sulfonamides / Q000097:blood* / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib