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

被引：40

作者：

Fox, Elizabeth ^{[1
]}

Jayaprakash, Nalini ^{[2
]}

Pham, Tuyet-Hang ^{[3
]}

Rowley, Ayana ^{[3
]}

McCully, Cynthia L. ^{[2
]}

Pucino, Frank ^{[3
,4
]}

Goldbach-Mansky, Raphaela ^{[3
]}

机构：

[1] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[2] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA

[3] NIAMSD, NIH, Bethesda, MD 20892 USA

[4] US FDA, Ctr Drug Evaluat & Res, DHHS, Silver Spring, MD USA

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2010年 / 223卷 / 1-2期

关键词：

IL-1Ra; IL-1; Anakinra; Pharmacokinetics; NOMID; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BRAIN; BLOOD; PLASMA;

D O I：

10.1016/j.jneuroim.2010.03.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：138 / 140

页数：3

共 20 条

[1]

BACHER JD, 1994, LAB ANIM SCI, V44, P148

[2]

Passage of cytokines across the blood-brain barrier [J].

Banks, WA ;

Kastin, AJ ;

Broadwell, RD .

NEUROIMMUNOMODULATION, 1995, 2 (04) :241-248

[3]

BANKS WA, 1991, J PHARMACOL EXP THER, V259, P988

[4]

Interleukin-1 receptor antagonist penetrates human brain at experimentally therapeutic concentrations [J].

Clark, Simon R. ;

McMahon, Catherine J. ;

Gueorguieva, Iva ;

Rowland, Malcolm ;

Scarth, Sylvia ;

Georgiou, Rachel ;

Tyrrell, Pippa J. ;

Hopkins, Stephen J. ;

Rothwell, Nancy J. .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2008, 28 (02) :387-394

[5]

Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation [J].

Dinarello, CA .

CURRENT OPINION IN PHARMACOLOGY, 2004, 4 (04) :378-385

[6]

Zidovudine concentration in brain extracellular fluid measured by microdialysis: Steady-state and transient results in rhesus monkey [J].

Fox, E ;

Bungay, PM ;

Bacher, J ;

McCully, CL ;

Dedrick, RL ;

Balis, FM .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 301 (03) :1003-1011

[7]

Gibaldi M., 1982, Pharmacokinetics, V2, P445

[8]

Treatment of patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome: Comment on the article by Matsubara et al [J].

Goldbach-Mansky, Raphaela ;

Pucino, Frank ;

Kastner, Daniel L. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (06) :2099-2101

[9]

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition [J].

Goldbach-Mansky, Raphaela ;

Dailey, Natalie J. ;

Canna, Scott W. ;

Gelabert, Ana ;

Jones, Janet ;

Rubin, Benjamin I. ;

Kim, H. Jeffrey ;

Brewer, Carmen ;

Zalewski, Christopher ;

Wiggs, Edythe ;

Hill, Suvimol ;

Turner, Maria L. ;

Karp, Barbara I. ;

Aksentijevich, Ivona ;

Pucino, Frank ;

Penzak, Scott R. ;

Haverkamp, Margje H. ;

Stein, Leonard ;

Adams, Barbara S. ;

Moore, Terry L. ;

Fuhlbrigge, Robert C. ;

Shaham, Bracha ;

Jarvis, James N. ;

O'Neil, Kathleen ;

Vehe, Richard K. ;

Beitz, Laurie O. ;

Gardner, Gregory ;

Hannan, William P. ;

Warren, Robert W. ;

Horn, William ;

Cole, Joe L. ;

Paul, Scott M. ;

Hawkins, Philip N. ;

Pham, Tuyet Hang ;

Snyder, Christopher ;

Wesley, Robert A. ;

Hoffmann, Steven C. ;

Holland, Steven M. ;

Butman, John A. ;

Kastner, Daniel L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (06) :581-592

[10]

GOLDBACHMANSKY R, 2007, ARTHRITIS RHEUM, V56, P2101

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