Influence of analogues of phenylbutazone on renal transport of 4-aminohippurate

Analogues of phenylbutazone were tested for inhibitory potency in the renal transport mechanism for 4-aminohippurate. In a series of ten compounds examined by an in vitro technique, no correlation could be demonstrated between inhibitory potency and acidic strength of the inhibitor either in rabbit or in dog tissues. In a further series of 16 paired analogues, the hydroxylated member of each pair was 3–4 times less potent than its unhydroxylated counterpart. Correlations between molecular structure and pharmacological activity are suggested. In contrast to these observations, each of three selected phenylbutazone analogues (phenylbutazone, metabolite II, and sulfinpyrazone) depressed the maximum tubular excretory rate for 4-aminohippurate in intact dogs, but apparent inhibitory potencies by the clearance technique were unrelated to inhibitory potencies in dog kidney slices. Differences in relative potencies thus obtained are attributed to differences in metabolic alteration of each compound at extrarenal sites in intact dogs.