Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections
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Open Access
- 1 October 2010
- journal article
- review article
- Published by American Society for Microbiology in Clinical Microbiology Reviews
- Vol. 23 (4), 858-883
- https://doi.org/10.1128/cmr.00007-10
Abstract
SUMMARY: The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.Keywords
This publication has 209 references indexed in Scilit:
- Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV‐associated cryptococcal meningitis‐infected patientsHIV Medicine, 2010
- Penetration of Colistin into Cerebrospinal FluidAntimicrobial Agents and Chemotherapy, 2009
- Darunavir Concentrations in Cerebrospinal Fluid and Blood in HIV-1–Infected IndividualsAIDS Research and Human Retroviruses, 2009
- Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug BindingScience, 2009
- Pharmacokinetic issues for antibiotics in the critically ill patientCritical Care Medicine, 2009
- Modulation of P-Glycoprotein at the Blood-Brain Barrier: Opportunities to Improve Central Nervous System PharmacotherapyPharmacological Reviews, 2008
- Plasma and Cerebrospinal Fluid Pharmacokinetics of Moxifloxacin in a Patient with Tuberculous MeningitisAntimicrobial Agents and Chemotherapy, 2008
- Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous SystemArchives of Neurology, 2008
- The Pharmacokinetics and Pharmacodynamics of Micafungin in Experimental HematogenousCandidaMeningoencephalitis: Implications for Echinocandin Therapy in NeonatesThe Journal of Infectious Diseases, 2008
- Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular DrainsAntimicrobial Agents and Chemotherapy, 2007