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Published byΕυάγγελος Ελευθερόπουλος Modified over 5 years ago
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Effects of inhibitors of drug efflux pumps on the penetration of antibiotics into the central nervous system. Effects of inhibitors of drug efflux pumps on the penetration of antibiotics into the central nervous system. (A) Concentration of radioactively labeled benzylpenicillin (BP) in the cisterna magna (CM) and the cisterna basalis (CB) after its application into the CM in control and probenecid-pretreated dogs. Concentrations of benzylpenicillin (means ± standard errors of the means [SEM]; n = 4) in the CM and CB over time (minutes), expressed as the percentage of the concentration in the CM at 5 min after drug application. Inhibition of the efflux pump by probenecid increases the CSF concentrations by a factor of 3 to 15. (Reproduced from reference 253 with permission of Elsevier B.V.) (B) Increased drug concentrations in P-glycoprotein knockout mice (149). The percent increases (concentration in knockout mice divided by the concentration in wild-type mice) in brain (dark blue bars) and plasma (light blue bars) for different drugs investigated by Schinkel and coworkers are shown. Contrarily to brain levels, plasma concentrations were not changed substantially, indicating a key role for P-gp at the blood-brain/blood-CSF barrier. (Reproduced from reference 149 with permission of the American Society for Pharmacology and Experimental Therapeutics.) Roland Nau et al. Clin. Microbiol. Rev. 2010; doi: /CMR
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