Vancomycin (VCM) is an important antibiotic for treating methicillin-resistant Staphylococcus aureus (MRSA) infections. To treat bacterial meningitis caused by MRSA, it is necessary to deliver VCM into the meninges, but the rate of VCM
translocation through the blood-brain barrier is poor. Additionally, high doses of intravascularly (i.v.) administered VCM may cause renal impairments. Thus, VCM is sometimes administered intracerebroventricularly (i.c.v.) for clinical treatment. However, information on the VCM pharmacokinetics in cerebrospinal fluid (CSF) after
i.c.v. administration is lacking. In the present study, we evaluated the VCM pharmacokinetics in the CSF and systemic circulation after i.c.v. compared to that after i.v. administration, using the brain microdialysis method in mice. VCM administered
via i.c.v. showed a highly selective distribution in the CSF, without migration to systemic circulation. Moreover, to assess renal impairments after i.c.v. administration of VCM, we histologically evaluated damage to the mouse kidney by hematoxylin and eosin staining. No significant morphological change in the kidney was observed in the i.c.v. administration group compared to that in the i.v. administration group. Our results
demonstrate that i.c.v. administration of VCM can be partially prevented from entering the systemic circulation to prevent renal impairments caused by VCM.
雑誌名
AAPS PharmSciTech
巻
20
号
1
ページ
5
発行年
2018-12-17
出版者
Springer International Publishing
EISSN
15309932
DOI
10.1208/s12249-018-1232-8
権利
c 2018, American Association of Pharmaceutical Scientists.
The original publication is available at www.springerlink.com.
Brain Microdialysis Study of Vancomycin in the Cerebrospinal Fluid After Intracerebroventricular Administration in Mice
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