Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.
Gout is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected (Podagra) in about half of cases. It may also result in tophi, kidney stones, or kidney damage.
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken orally or intravenously.
Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids in the treatment of gout. Other uses for colchicine include the management of pericarditis.
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for males, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.
The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:
Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It is taken by mouth.
Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule of the kidney. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms.
Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.
Febuxostat, sold under the brand name Uloric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. It is taken by mouth.
Solute carrier family 22, member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.
Benzbromarone is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone.
Colestilan is a medication that acts as a phosphate binder and bile acid sequestrant. It is an ion-exchange resin, is an orally administered bile acid sequestrant that is being developed by Mitsubishi Tanabe Pharma Corporation for the treatment of hypercholesterolaemia and hyperphosphataemia. It has been launched in Japan for hypercholesterolaemia. For the treatment of hyperphosphataemia, it is launched in Austria, Germany, the Czech Republic, Portugal and the United Kingdom, is registered in the EU. Phase III development in paediatric patients with hyperphosphataemia associated with chronic kidney disease was underway in the UK and Germany. However, the company discontinued the development. In addition, the phase II development in type-2 diabetes mellitus and phase I development in hyperphosphataemia, in Japan, was also discontinued by the company.
Pegloticase is a medication for the treatment of severe, treatment-refractory, chronic gout. It is a third line treatment in those in whom other treatments are not effective or are not tolerated. The drug is administered by infusion intravenously. Since October 2023, Amgen Inc. has been the marketer of pegloticase in the U.S.
Topiroxostat is a drug for the treatment of gout and hyperuricemia. It was approved for use in Japan in June 2013.
Lesinurad is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is recommended only as an adjuvant with either allopurinol or febuxostat when these medications are not sufficient.
Dotinurad (Urece) is a drug for the treatment of gout and hyperuricemia. It was developed by Fuji Yakuhin and approved for use in Japan in 2020. The drug is continuing clinical trials by Fortress Biotech and regulatory evaluation for approval in North America and Europe.
Ruzinurad (SHR4640) is a selective urate transporter 1 (URAT1) inhibitor in development for hyperuricaemia and gout. It is developed by Jiangsu Hengrui.
Gout suppressants are agents which control and prevent gout attacks after the first episode. They can be generally classified into two groups by their purpose: drugs used for induction therapy and that for maintenance therapy.
Renal tubular transport inhibitors are a class of drugs that interfere with the function of specific transporters in the renal proximal tubules, affecting the excretion and reabsorption of various substances, including drugs and endogenous compounds. These inhibitors target membrane transport proteins expressed in kidney tubule epithelial cells, which play a crucial role in drug elimination and can significantly influence drug pharmacokinetics. By modulating the activity of transporters such as organic anion transporters (OATs), organic cation transporters (OCTs), and multidrug and toxin extrusion proteins (MATEs), these inhibitors can alter the renal clearance of drugs, potentially leading to clinically significant drug-drug interactions (DDIs) and changes in drug efficacy or toxicity. Renal tubular transport inhibitors have both therapeutic applications, such as enhancing the efficacy of certain medications or reducing drug-induced nephrotoxicity, and potential risks, including unwanted drug accumulation and altered pharmacokinetics of co-administered drugs.
