Inhibition of probenecid uricosuria by pyrazinamide and para-aminohippurate

Both para-aminohippurate (PAH) and pyrazinamide inhibited the uricosuric response to probenecid administration. The mechanism of this inhibition of probenecid uricosuria was assessed in 18 male subjects. The decrease in uricosuria was assessed in 18 male subjects. The decrease in uricosuric response to probenecid observed after pyrazinamide administration or PAH infusion occurs by different mechanisms. Administration of PAH and probenecid together resulted in reduced excretion of both drugs. PAH was weakly uricosuric and did not appear to inhibit urate secretion. PAH inhibition of probenecid uricosuria is accounted for by inhibition of probenecid secretion. Probenecid excretion was not affected by pyrazinamide administration. Inhibition of probenecid-induced uricosuria by pyrazinamide is most likely due to inhibition of urate secretion. The urate secretory carrier inhibited by pyrazinamide appears to be independent of that responsible for secretion of probenecid and PAH. Probenecid secretion appears to be required for its uricosuric effect.