Inhibition of probenecid uricosuria by pyrazinamide and para-aminohippurate
Meisel, A.D.; Diamond, H.S.
American Journal of Physiology 232(3): F222-F226
1977
ISSN/ISBN: 0002-9513 PMID: 842669 Document Number: 115351
Both p-aminohippurate (PAH) and pyrazinamide inhibited the uricosuric response to probenecid administration. The mechanism of this inhibition of probenecid uricosuria was assessed in 18 men from 18-61 yr old. The decrease in uricosuric response to probenecid observed after pyrazinamide administration or PAH infusion occurred 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 was accounted for by inhibition of probenecid secretion. Probenecid excretion was not affected by pyrazinamide administration. Inhibitoon of probenecid-induced uricosuria by pyrazinamide was most likely due to inhibition of urate secretion. The urate secretory carrier inhibited by pyrazinamide may be independent of that responbile for secretion of probenecid and PAH. Probenecid secretion may be required for its uricosuric effect.