Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates

Cancer Chemother Pharmacol. 2010 Feb;65(3):419-25. doi: 10.1007/s00280-009-1044-3. Epub 2009 Jun 13.


Purpose: ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration.

Methods: ABT-888, 5 mg/kg, was administered orally to three NHPs. Serial blood and CSF samples were obtained. Plasma and CSF concentrations of ABT-888 were measured using LC/MS/MS, and the resulting concentration versus time data were evaluated using non-compartmental and compartmental PK methods.

Results: The CSF penetration of ABT-888 was 57+/-7% (mean+/-SD). The peak ABT-888 concentration in the plasma was 0.62+/-0.18 microM. Plasma and CSF AUC0-infinity were 3.7+/-1.7 and 2.1+/-0.8 microM h. PARP inhibition in peripheral blood mononuclear cells was evident 2 h after ABT-888 administration.

Conclusion: The CSF penetration of ABT-888 after oral administration was 57%. Plasma and CSF concentrations were in the range that has been shown to inhibit PARP activity in vivo in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Benzimidazoles / blood*
  • Benzimidazoles / cerebrospinal fluid*
  • Benzimidazoles / pharmacokinetics
  • Humans
  • Leukocytes, Mononuclear / enzymology
  • Macaca mulatta
  • Male
  • Metabolic Clearance Rate
  • Molecular Structure
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Time Factors


  • Benzimidazoles
  • Poly(ADP-ribose) Polymerase Inhibitors
  • veliparib
  • Poly(ADP-ribose) Polymerases