Penetration of the blood brain barrier by metronidazole and tinidazole

Abstract

Since few drugs are available for the treatment of anaerobic bacterial central nervous system infections, we studied the penetration of metronidazole and tinidazole into the cerebrospinal fluid (CSF). The lipid/water partition coefficients of both were high enough to suggest good penetration. In rabbits, CSF concentrations of either drug almost equalled simultaneous serum levels. In human volunteers 90 min after oral metronidazole (2.4 g) or tinidazole (2.0 g), the average CSF/serum ratio of biologically active metronidazole was 0.43 and that of tinidazole was 0.88. The lowest CSF concentrations were several fold higher than those needed to inhibit Bacteroides fragilis in vitro. These results encourage clinical trials of metronidazole or tinidazole in the treatment of central nervous system infections caused by anaerobic bacteria or amoebae.