The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates.
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.
Fox
Elizabeth
E
The Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, PA 19104, USA. Foxe@email.chop.edu
Jayaprakash
Nalini
N
Pham
Tuyet-Hang
TH
Rowley
Ayana
A
McCully
Cynthia L
CL
Pucino
Frank
F
Goldbach-Mansky
Raphaela
R
D000818:Animals; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000592:standards; D008253:Macaca mulatta; D008297:Male
D053590:Interleukin 1 Receptor Antagonist Protein