Using a high performance liquid chromatography assay, pyrazinamide and rifampicin concentrations were measured in paired samples of cerebrospinal fluid (CSF) and serum obtained 2, 5, and 8 hours after oral drug administration in 12 patients with tuberculous meningitis. Penetration of pyrazinamide into CSF was good, with the CSF concentration exceeding that of serum by five to eight hours. The maximum CSF concentration achieved was mcre than twice the minimum inhibitory concentration (MIC) for 85% of local strains of Mycobacterium tuberculosis. Penetration appeared greater at five hours in the earlier stages of the disease. By contrast, penetration of rifampicin was comparatively poor, the maximum concentration reached in the CSF being only one tenth that of serum at eight hours. Moreover, the level did not reach MICs for 20% of local strains of M tuberculosis. Penetration appeared to be proportional to the extent of meningeal inflammation as assessed by CSF protein concentration and white cell count. Use of steroids did not appear to influence either pyrazinamide or rifampicin penetration into the CSF. It is concluded that with the present oral dosages of pyrazinamide (31 to 33 mg/kg), adequate CSF levels are reached. However, for rifampicin, (mean dose, 11 to 12 mg/kg), the CSF concentration may not reach the MIC in a proportion of patients, so that further studies are needed to determine optimum dosage and method of drug administration in order to achieve therapeutic CSF levels.
- CSF levels,
- serum levels,
- tuberculous meningitis
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