Sign Out
Pharmacology: Pharmacodynamics: Febuxostat is a xanthine oxidase inhibitor, which is selective for xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. By blocking uric acid production, febuxostat decreases serum concentration of uric acid. Febuxostat has no effect on other enzymes involved in purine and pyrimidine synthesis and metabolism, namely guanine deaminase, hypoxanthine-guanine phosphoribosyltransferase, purine nucleoside phosphorylase, orotate phosphoribosyltransferase and orotidine-5 V-monophosphate decarboxylase.
Pharmacokinetics: Absorption: Febuxostat is well (about 85%) and rapidly absorbed after oral doses which time of peak plasma concentration (tmax) is 1.5 hours. Cmax increases proportionally with dose within the dose range of 10-240 mg. The absolute availability of febuxostat has not been directly determined. Although dosage with a high-fat meal decreases peak plasma concentration, this is not thought clinically significant, and febuxostat may be taken with or without food.
Distribution: Febuxostat is highly bound (98-99%) to plasma proteins, mainly to albumin and has a low to moderate Vss/F (steady state volume of distribution) of 48 ± 23 L.
Metabolism: Febuxostat is metabolized directly by glucuronidation (up to 40%) mainly via uridine diphosphate-glucuronosyltransferase (UGT), namely UGT1A1, UGT1A8, UGT1A9 forming the febuxostat-acyl glucuronide. About 35% of febuxostat is metabolised by oxidation via cytochrome P450, including CYP1A1, CYP1A2, CYP2C8 and CYP2C9.
Elimination: Febuxostat is excreted in urine and faeces. Approximately 49% of the total drug is recovered in the urine. About 30% of the dose excreted in urine is the glucuronide, being the parent drug about 3% and approximately 12% is excreted as oxidative metabolites. Besides excreted in urine, about 45% of dose is recovered in faeces. Approximately 25% of the dose is excreted in faeces as the oxidised metabolites and about 12% as unchanged febuxostat.
