Research Article Critique

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Topics: Uric acid, Gout
RUNNING HEAD: Critical Analysis

Critical Analysis Paper
Arminda Combs
Graduate Pharmacology
Dr. Thornburg * * * * * * * * * * * * * * * * * * * * * *

Background Uloric (febuxostat) is a xanthine oxidase inhibitor indicated for the chronic management of hyperuricemia in patients with gout. Its mechanism of action is the inhibition of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. At therapeutic concentrations it does not inhibit other enzymes involved in purine and pyrimidine synthesis. Its key pharmological action is that is reduces serum uric acid levels in the body. Uloric’s pharmacodynamic properties include a dose dependent decrease in 24-hour mean serum uric acid concentrations and an increase in 24-hour mean serum xanthine concentrations. In addition, it decreases daily urinary uric acid excretion and an increase in total daily urinary xanthine excretion. Percent reduction in 24-hour mean serum uric acid concentrations was between 40% and 55% at the exposure levels of 40 mg and 80 mg daily doses (Takeda, 2009). Pharmacokinetic properties include and absorption rate estimated at 49%. The mean apparent steady state volume of distribution is approximately 50 L (CV ~40%). Protein binding is approximately 99.2%; primarily to albumin. Metabolism includes conjugation via uridine diphosphate glucuronosyltransferases (UGTs) 1A1, 1A3, 1A9, and 2B7 and oxidation via cytochrome P450 (CYP) 1A2, 2C8, and 2C9 as well as non-P450 enzymes. Oxidation leads to formation of active metabolites (67M-1, 67M-2, 67M-4). The contribution of each enzyme in the metabolism of Uloric is not fully understood. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxy metabolites. In urine and feces, acyl glucuronide metabolites of Uloric (~35% of the



References: * Febuxostat tablets (uloric®). (2009). Internal Medicine Alert, * * N.A. Uloric. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013.

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