Inhibition of purine catabolism by benzbromarone in isolated rat liver cells. Comparison with allopurinol and probenecid.
Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regulation of this pathway. We found that allopurinol is several times superior to benzbromarone in the lowering of allantoin production (if they are compared in terms of their relative therapeutic levels), and that probenecid had no effect on it.
Rodilla
F
F
Departament de Bioquimica i Biologia Molecular, Facultat de Farmacia, Universitat de Valencia, Spain.
Sanchez-Beltran
M J
MJ
Izquierdo
R
R
Gomez-Ruiz
M D
MD
Cabo
J
J
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001553:Benzbromarone / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014527:Uric Acid / Q000097:blood
D001572:Benzofurans; D011687:Purines; D014527:Uric Acid; D001553:Benzbromarone; D000493:Allopurinol; D011339:Probenecid