Concentrações sanguíneas de pirazinamida e ácido úrico em pacientes em tratamento para tuberculose

Abstract

Pulmonary tuberculosis is a relevant public health problem in Brazil, where despite the measures of prophylaxis used, there is a high number of cases.The treatment is carried out in two stages: the intensive one, when combined fixed-dose tablets composed of rifampicin, isoniazid, pyrazinamide and ethambutol are administered and the maintenance phase with the use of rifampicin and isoniazid. This is effective in most cases of the disease, however, adverse reactions contribute to non- adherence to treatment, which can lead to therapeutic failure. Pyrazinamide is considered the most hepatotoxic drug, and causes several adverse reactions, such as hyperuricemia, however, few studies have investigated this reaction, which is relevant, because when accompanied by pain symptoms it can lead to treatment abandonment. The aim of this study was to measure plasma concentrations of pyrazinamide, by liquid chromatography of high- performance, and measure the serum acid uric levels, by spectrophotometry, in 44 patients positive by clinical, laboratory, and imaging tests. The measurement assay was done at the end of the intensive treatment phase. Most of the patients were men, with low education and low monthly income. The median daily doses of pyrazinamide administered was 26.2 (22.9-29.7) mg/kg to male patients and 26.8 (23.2-30.8) mg/kg to female. Plasma concentrations of pyrazinamide was 42 (10- 168) µg/mL to men and 50.5 (10-110) µg/mL (P <0.05) in women. The median of plasma concentrations was higher than the minimum inhibitory concentration for sensitive strains of the bacillus. The proportions of patients with serum uric acid levels above the normal range were 75% to female and 44.4% to male, with median values of 7.6 mg/dL and 7.4 mg/dL, respectively. Patient’s weight was not considered as a predictor of plasma pyrazinamide concentrations. The plasma pyrazinamide concentrations and the administered dose, expressed in mg/kg, were not associated with serum uric acid levels. The results of the present study demonstrate that the doses of pyrazinamide provide plasma concentrations that ensure adequate exposure of the bacillus to the drug. Acid uric levels were increased in the patients of this study, probably caused by the metabolites of pyrazinamide.