Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 3, pp 387–392 | Cite as

The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates

  • Holly J. Meany
  • Elizabeth Fox
  • Cynthia McCully
  • Chris Tucker
  • Frank M. Balis
Original Article



Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model.


Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUCCSF:AUCplasma.


Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m2. OSI-420 exposure (AUC) in plasma was 30% (range 12–59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUCCSF:AUCplasma) of erlotinib and OSI-420 was <5% relative to total plasma concentration, but CSF drug exposure was ∼30% of plasma free drug exposure, which was calculated from published plasma protein binding values. The IV administration of erlotinib was well tolerated.


Erlotinib and its active metabolite OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.


Erlotinib Pharmacokinetics Cerebrospinal fluid Non-human primate 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Holly J. Meany
    • 2
  • Elizabeth Fox
    • 1
  • Cynthia McCully
    • 1
  • Chris Tucker
    • 3
  • Frank M. Balis
    • 1
  1. 1.Pediatric Oncology BranchNational Cancer InstituteBethesdaUSA
  2. 2.Children’s National Medical CenterWashingtonUSA
  3. 3.OSI PharmaceuticalsBoulderUSA

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