RESUMO
A direct in-line pre-column extraction technique in which guanidinium and ammonium sulfate are used, followed by column switching, was employed to analyze serum, plasma and cerebrospinal fluid samples of patients treated for tuberculous meningitis. Resolution of a wide range of polar to non-polar xenobiotics was obtained on a C8 silica column by using a linear gradient from a binary system consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol, 4:1, v/v). Apart from the antituberculosis drugs (isoniazid, pyrazinamide, ethionamide and rifampicin) the patients received up to sixteen different medicines for prevention of complications and the treatment of symptoms. Qualitative resolution of all the drugs was obtained by the chromatographic system. Quantitation of pyrazinamide and ethionamide was achieved with high precision and low inter-sample variation.
Assuntos
Antituberculosos/análise , Antituberculosos/sangue , Antituberculosos/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão , Monitoramento de Medicamentos , Etionamida/análise , Etionamida/sangue , Etionamida/líquido cefalorraquidiano , Humanos , Isoniazida/análise , Isoniazida/sangue , Isoniazida/líquido cefalorraquidiano , Pirazinamida/análise , Pirazinamida/sangue , Pirazinamida/líquido cefalorraquidiano , Espectrofotometria Ultravioleta , Tuberculose Meníngea/sangue , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Xenobióticos/sangue , Xenobióticos/líquido cefalorraquidianoRESUMO
Cerebrospinal fluid ethionamide concentrations were determined in 18 children (median age 26.5 months) with tuberculous meningitis complicated by raised intracranial pressure. Lumbar spinal fluid specimens were obtained before and after weekly hour-long monitoring of intracranial pressure. Thirty-five paired and four single specimens were evaluated. A dosage schedule of 15 mg/kg was used on 26 occasions, and a spinal fluid ethionamide concentration of 2.5 micrograms/ml, the in vitro minimal inhibitory concentration for Mycobacterium tuberculosis, was exceeded on only seven occasions (27%). A dosage of 20 mg/kg was administered on 13 occasions, and in only two instances (15%) was a concentration of 2.5 micrograms/ml not achieved. Ethionamide in a single daily dosage of 20 mg/kg should be considered for the initial treatment of tuberculous meningitis when the presence of isoniazid-resistant M. tuberculosis cannot be excluded.
