PROBENECID METABOLISM INVITRO WITH RAT, MOUSE, AND HUMAN LIVER PREPARATIONS - STUDIES OF FACTORS AFFECTING SITE OF OXIDATION

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (2) , 205-210
Abstract
The metabolism of probenecid [a uricosuric agent] in vitro was investigated with rat, mouse and human liver preparations. As in previous in vivo studies, metabolism in vitro was limited to the side chain. This metabolism involved mono-N-depropylation and hydroxylation in the 2- and 3-positions (3-hydroxy probenecid was in part converted to the carboxy metabolite). Acyl glucuronide conjugation was minimal. The presence of multiple forms of microsomal oxidative enzymes was suggested by the effects of phenobarbital pretreatment, drug-metabolizing enzyme inhibitors, and variations in ionic strength and buffer composition on the metabolism of probenecid.