Is there any clinically relevant interaction between probenecid and azathioprine?

Fråga: Is there any clinically relevant interaction between probenecid and azathioprine?

Sammanfattning: No interaction between probenecid and azathioprine in man has been reported. In rat models probenecid has been reported to inhibit the conversion of azathioprine to 6-mercaptopurine indicating the involvement of glutathione S-transferase in this metabolic conversion. The clinical relevance of such a possible interaction, if it exists in man, remains unclear.

Svar: No clinical reports of interaction between probenecid and azathioprine have been found in the literature. However, two relatively old studies in rats have reported an effect of probenecid on azathioprine elimination. Hobara and Watanabe (1) reported that probenecid which is an inhibitor of glutathione S-transferase decreased the metabolic elimination of azathioprine in the rat. The urinary excretion of azathioprine was also inhibited by probenecid. However, the urinary excretion of unmetabolized azathioprine over 12 hours was only less than two per cent. Thus, the authors concluded that the inhibition of urinary azathioprine excretion by probenecid treatment may not have been the only reason for the decreased clearance of azathioprine from blood. Kaplowitz and Kuhlenkamp (2) reported that the conversion of azathioprine to 6-mercaptopurine was inhibited in vivo by pretreating rats with probenecid as indicated both by less hepatic glutathione depletion and by a greater proportion of unmetabolized azathioprine in the liver. The relevance of these studies for the treatment with probenecid and azathioprine in man remains unclear and no later studies on the issue have been found in the literature.