The influence of sex on pyrazinamide and uric acid serum levels in Brazilian patients treated for pulmonary tuberculosis

Adverse reactions to antituberculosis drugs can lead to treatment abandonment, prolonging the burden of the disease. The role of sex in pyrazinamide exposure and uric acid metabolism raises questions about its influence on the rates of arthralgia and hyperuricemia in patients with tuberculosis. Given the limited evidence in the literature regarding sex-related differences in adverse reaction rates, this study compares serum levels of pyrazinamide and uric acid, as well as the rates of hyperuricemia and arthralgia, between male and female patients with pulmonary tuberculosis. Uric acid levels were measured using the spectrophotometric uricase method, and serum pyrazinamide levels were determined by high-performance liquid chromatography. A total of 88 patients were enrolled in the study. The mean weight, pyrazinamide dosage, and median uric acid levels were similar between sexes. However, the proportion of males with hyperuricemia was higher than that of females. Pyrazinamide maximum concentrations ranged from 10 to 98 µg/mL and were higher in females than in males. The overall rate of arthralgia was 25%, occurring primarily in male patients with hyperuricemia. Serum pyrazinamide levels were higher in patients with arthralgia compared to those without it. No significant correlations were found between drug levels and uric acid in either sex. In conclusion, sex influences pyrazinamide exposure and arthralgia and hyperuricemia rates. Close monitoring of uric acid levels may help improve adherence to tuberculosis therapy.