Abstract
The metabolism of probenecid in vitro was investigated with rat, mouse, and human liver preparations. As in previous in vivo studies, metabolism in vitro was found to be 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: a) phenobarbital pretreatment, b) drug-metabolizing enzyme inhibitors, and c) variations in ionic strength and buffer composition on the metabolism of probenecid.
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Probenecid metabolism in vitro with rat, mouse, and human liver preparations. Studies of factors affecting the site of oxidation.
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