Benzbromarone disposition and uricosuric action; evidence for hydroxilation instead of debromination to benzarone.
Benzbromarone is one of the main uricosuric drugs currently used. We determined plasma concentrations of benzbromarone, bromobenzarone, and benzarone and 24 hour uric acid excretion in ten healthy individuals following fasting application of two different non-micronised benzbromarone brands. In addition we explored the influence of adjusting urinary pH to near neutral values and of concomitant food intake. Benzbromarone was more rapidly absorbed from the test preparation than from the reference preparation; the extent of systemic availability did not differ significantly. Urinary pH adjustment had no clearcut effect, whereas food intake retarded drug absorption (even though not significant because of the variability of the data). Binding of benzbromarone to plasma proteins exceeded 99%. Bromobenzarone and benzarone were not detectable and are unlikely to be major metabolites of benzbromarone. Instead we found two other compounds suggestive of metabolites, one of them being monohydroxilated benzbromarone. The plasma concentrations of the parent compound in one subject exceeded those of the rest of the group, possibly indicating genetic differences in drug metabolism. The uricosuric effect was not related to benzbromarone plasma concentrations.
Walter-Sack
I
I
Abteilung Klinische Pharmakologie, Universität Heidelberg.
de Vries
J X
JX
Ittensohn
A
A
Kohlmeier
M
M
Weber
E
E
D000328:Adult; D001553:Benzbromarone / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D001572:Benzofurans / Q000493:pharmacokinetics*; D006801:Humans; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D008297:Male; D011485:Protein Binding; D011687:Purines / Q000008:administration & dosage; D014527:Uric Acid / Q000652:urine*
D001572:Benzofurans; D011687:Purines; C004528:benzarone; D014527:Uric Acid; D001553:Benzbromarone; C055946:bromobenzarone