The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates.

ABSTRACT

Anakinra improves the central nervous system manifestations of neonatal-onset multisystem inflammatory disease, which is mediated by IL-1beta oversecretion. The cerebrospinal fluid (CSF) penetration of the IL-1 receptor antagonist anakinra was studied in rhesus monkeys after intravenous doses of 3 and 10 mg/kg. Drug exposure (area under concentration-time curve) in CSF was 0.28% of that in serum. The average CSF concentration at 3 mg/kg was 1.8 ng/mL, which is 30-fold higher than endogenous CSF levels of IL-1Ra. The CSF penetration was not dose-dependent, indicating that the CSF penetration was not saturated in the 3 to 10 mg/kg dose range.