Penetration of rifampicin into the cerebrospinal fluid of adults with uninflamed meninges.

The penetration of rifampicin into CSF was studied in seven patients who had undergone external ventriculostomy for occlusive hydrocephalus without major disturbance of the blood-CSF barrier. After the first dose of rifampicin 600 mg i.v. over 3 h, blood and CSF concentrations were determined serially by HPLC. Peak CSF concentrations obtained 0-8 h (median = 1 h) after the end of the infusion ranged from 0.57 to 1.24 mg/L (median = 0.73 mg/L). Elimination from CSF was slower than from serum (T1/2 beta CSF: 9.1-21.0 h (median = 14.5 h, n = 5); T1/2 beta serum: 2.2-5.8 h (median = 3.6 h, n = 7)). Based on the ratios of the areas under the concentration-time curves in CSF and serum, the overall penetration of rifampicin into CSF was 0.13-0.42 (median = 0.22). These results demonstrate effective CSF penetration and favourable pharmacokinetics of rifampicin in the absence of meningeal inflammation. They support the use of rifampicin as part of a combination therapy not only for tuberculosis of the central nervous system (CNS), but also for staphylococcal and listerial infections of the CNS in which there may be little meningeal inflammation.