Pegloticase is used in tophaceous gout refractory to conventional urate-lowering therapy. It reduces urate by:

• A Inhibiting xanthine oxidase with a potency 1000-fold greater than allopurinol
• B Catalyzing the oxidation of uric acid to allantoin (a more soluble product) using recombinant pegylated porcine uricase, an enzyme absent in humans ✓
• C Activating ABCG2 urate transporter in renal tubules, increasing urate excretion
• D Competitively inhibiting URAT1 transporter in proximal tubule, reducing urate reabsorption

Explanation

Humans and higher primates lack functional uricase (urate oxidase) due to an evolutionary mutation, making uric acid the end product of purine catabolism. Pegloticase is a recombinant pegylated mammalian (porcine/baboon chimeric) uricase that catalyzes the enzymatic oxidation of uric acid to allantoin, which is 5–10 times more soluble and easily excreted. This dramatically reduces serum urate. PEGylation extends half-life and reduces immunogenicity. However, loss of efficacy occurs when antibodies develop against the enzyme. URAT1 inhibition is the mechanism of lesinurad/benzbromarone.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.