Plasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates

Jamie Renbarger, Alexander Aleksic, Leticia McGuffey, Robert Dauser, Stacey Berg, Susan Blaney

Research output: Contribution to journalArticle

10 Scopus citations


Purpose: SU5416 is a small, lipophilic synthetic molecule that selectively inhibits the tyrosine kinase activity of the VEGF receptor Flk-1/KDR. The role of this agent in brain tumors is currently being investigated. Pharmacokinetic studies of SU5416 have been performed in humans; however, there have been no studies of its penetration in the cerebrospinal fluid (CSF). We studied the pharmacokinetics of SU5416 in plasma and CSF after intravenous (i.v.) administration using a nonhuman primate model that is highly predictive of the CSF penetration in humans. Experimental design: SU5416 (85 mg/m2, about 3.8 mg/kg) was administered i.v. over 20 min to four nonhuman primates. Serial plasma and CSF samples were obtained prior to, during, and after completion of the infusion for determination of SU5416 concentrations. SU5416 was measured in plasma and CSF using high-performance liquid chromatography (HPLC). Concentration-versus-time data were modeled using model-independent and model-dependent methods. Results: Peak plasma concentrations ranged from 6.3 to 14.5 μM and the mean plasma AUC was 620 ± 180 μM·min. Disappearance of SU5416 from the plasma was best described by a one-compartment model with a half-life of 39 ± 2.9 min. The volume of distribution was 36 ± 11 l/m2 and the clearance was 0.62 ± 0.2 l/min per m2. SU4516 was not quantifiable in the CSF. Conclusions: There is minimal penetration of SU5416 into the CSF after i.v. administration. The very low CNS exposure to SU5416 after i.v. dosing suggests that this agent is not optimal for the treatment of leptomeningeal tumors.

Original languageEnglish (US)
Pages (from-to)39-42
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Issue number1
StatePublished - Jan 1 2004
Externally publishedYes


  • Antiangiogenesis
  • Leptomeningeal malignancy
  • SU5416

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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