Role of rifampicin in arthralgia induced by pyrazinamide

Abstract

Arthralgia during daily treatment with chemotherapy regimens containing pyrazinamide was found to be considerably less in patients who received rifampicin concomitantly. The effect of rifampicin on the biodisposition of pyrazinamide, and the pyrazinamide-induced changes in the renal elimination of uric acid was, therefore, investigated. In one investigation in tuberculous patients undergoing treatment with daily regimens containing pyrazinamide or pyrazinamide and rifampicin, serial serum concentrations of pyrazinamide and uric acid up to 11 hours, and urinary pyrazinamide, pyrazinoic acid and uric acid concentrations collected at intervals up to 11 1 2 hours after drug administration were determined. In a second investigation in healthy volunteers, the effect of single doses of rifampicin, pyrazinamide and a combination of the two drugs on the renal excretion of uric acid during a 24-hour period was determined. Results of the first investigation showed that the serum concentrations and the renal clearance of pyrazinamide were similar in patients receiving pyrazinamide or with or without rifampicin, suggesting that rifampicin had no effect on either the metabolism or excretion of pyrazinamide. Both investigations demonstrated that pyrazinamide caused a significant decrease in the renal excretion of uric acid. Rifampicin enhanced the renal excretion of uric acid, both in the presence and in the absence of pyrazinamide, and also that of pyrazinoic acid. This effect could lead to a decrease in the deposition of uric acid in joints, and consequently to a lower incidence of arthralgia.