The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates
The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates
复制标题
DOI：
10.1016/j.jneuroim.2010.03.022
复制
发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Goldbach-Mansky, Raphaela
中科院分区：
文献类型：
--
作者：
Fox, Elizabeth;Jayaprakash, Nalini;Goldbach-Mansky, Raphaela
阿那白能改善由IL-1 β过度分泌介导的新生儿多系统炎性疾病的中枢神经系统表现。研究了IL-1受体拮抗剂anakinra在静脉注射3和10 mg/kg后对恒河猴脑脊液（CSF）渗透的影响。脑脊液中药物暴露量（浓度-时间曲线下面积）为血清暴露量的0.28%。3 mg/kg时的平均CSF浓度为1.8 ng/mL，比内源性CSF IL-1Ra水平高30倍。脑脊液穿透不存在剂量依赖性，表明在3 ~ 10mg /kg剂量范围内脑脊液穿透不饱和。(C) 2010 Elsevier B.V.版权所有
Anakinra improves the central nervous system manifestations of neonatal-onset multisystem inflammatory disease, which is mediated by IL-1 beta 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. (C) 2010 Elsevier B.V. All rights reserved.