RT Journal Article
SR Electronic
T1 URICOSURIC POTENCY OF 2-SUBSTITUTED ANALOGS OF PROBENECID
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 397
OP 410
VO 180
IS 2
A1 K. C. Blanchard
A1 Dieter Maroske
A1 David G. May
A1 I. M. Weiner
YR 1972
UL http://jpet.aspetjournals.org/content/180/2/397.abstract
AB Probenecid and its 2-nitro, 2-hydroxyl and 2-chloro analogs were evaluated for uricosuric potency in monkeys, Cebus albifrons. The three analogs were approximately equipotent and about 10 times as potent as probenecid when compared on the basis of concentration of drug in plasma. There was no correlation between uricosuric potency and ability to inhibit secretion of p-aminohippurate. The three analogs were each secreted by an active transport mechanism, but the rates of excretion were not the same. The renal clearance of the nitro compound was considerably greater than the clearances of the other two analogs. All three analogs are considerably stronger acids than is probenecid. The results are evaluated in relation to a previously reported inverse correlation between uricosuric potency and pKa within a series of phenylbutazone analogs. © 1972 by The Williams & Wilkins Co.