Variation of benzbromarone elimination in man — a population study

Abstract

The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes.

Refractory Gout Attack

“…Therefore, we intended to maintain low and stable urate levels based on benzbromarone pharmacokinetics. This uricosuric agent is usually prescribed once daily because its metabolites have a half-life of 17–20 h [22, 23]. However, the peak action of this medication occurs within 4 hours following intake.…”

Personalized Medicine of Urate-Lowering Therapy for Gout

“…BBR undergoes hepatic hydroxylation to 1′-hydroxy BBR and 6-hydroxy BBR. The BBR elimination in serum was affected by genetic polymorphism in drug metabolism [71]. It was demonstrated that CYP2C9 was the main enzyme responsible for the 6-hydroxylation of BBR [72,73].…”

Benzbromarone hydroxylation in man: defective formation of the 6-hydroxybenzbromarone metabolite

“…Plasma concentrations and renal excretion of uric acid also were determined to establish possible correlations between drug plasma levels and uric acid metabolism, as reported previously [9]. In an earlier epidemiological [25] and in a family study [22] one of the volunteers included in the present investigation was found to be a slow eliminator of Bzbr, as determined by a single benzbromarone plasma concentration 24 h after drug administration.…”

“…Recently further metabolites of Bzbr have been characterized by gas chromatography -mass spectrometry in plasma after drug administration to humans [5,6] and in-vitro after incubation of Bzbr with human and rat liver microsomes [22,23]. In addition from the already known metabolites M1 and M2, further minor metabolites have been detected and characterized by gas chromatographymass spectrometry derivatization: metabolites M3, (l'-keto-Bzbr), M 4 (2'-hydroxybenzbromarone, an isomer of M0; M 5 (l',6-dihydroxybenzbromarone), M 6 (dihydroxy-aryl-benzbromarone), and M 7 and M 8 (isomers of M2) were detectable in all samples, although in different ratios.…”