Dotinurad is a medication developed for addressing conditions linked to elevated uric acid levels in the body. It was approved for use in Japan in 2020 and is currently undergoing clinical trials and regulatory evaluation for potential approval in North America and Europe. This drug provides a specific approach to managing conditions where uric acid buildup becomes a concern, aiming to restore balance within the body’s systems.
Understanding Dotinurad
Dotinurad is a medication used for hyperuricemia, a condition characterized by high levels of uric acid in the blood. This elevated uric acid can lead to the formation of urate crystals, which may accumulate in joints and other tissues, causing severe pain and inflammation, commonly known as gout. The drug is categorized as a selective uric acid reabsorption inhibitor (SURI).
As a SURI, dotinurad works by reducing the amount of uric acid that is reabsorbed back into the bloodstream by the kidneys. This action helps to lower serum uric acid levels, which is an important goal in preventing gout flares and other long-term complications associated with hyperuricemia, such as kidney stones.
How Dotinurad Works in the Body
Dotinurad operates by targeting a protein in the kidneys called urate transporter 1 (URAT1). URAT1 is located on the surface of kidney cells responsible for reabsorbing uric acid from the filtered fluid back into the blood. About 90% of the uric acid filtered by the kidneys is reabsorbed this way.
By inhibiting URAT1, dotinurad reduces this reabsorption process, leading to increased excretion of uric acid through urine. This selective action lowers uric acid levels in the blood. Dotinurad’s high selectivity for URAT1, while only weakly affecting other transporters involved in uric acid excretion, makes it effective in reducing serum uric acid. This mechanism decreases the urate pool in the body.
Dosing and Administration
Dotinurad is taken orally once daily. The usual starting dose for adults is 0.5 mg, which is gradually increased based on the patient’s blood uric acid levels. This gradual increase prevents gout flares from a rapid drop in uric acid.
The maintenance dose is 2 mg once daily, but it can be adjusted depending on the individual’s condition. The maximum recommended dose is 4 mg once a day. Clinical studies show that doses between 2 mg and 4 mg effectively reduce serum uric acid levels and maintain them over extended periods.
Potential Side Effects and Precautions
Dotinurad can cause side effects. Common side effects include gastrointestinal discomfort such as nausea, vomiting, diarrhea, or abdominal pain. Headaches, dizziness, and fatigue can also occur. These symptoms are usually mild and lessen as the body adjusts to the medication.
Allergic reactions, though rare, can occur and may present as rash, itching, swelling, or difficulty breathing, requiring immediate medical attention. Patients with pre-existing kidney conditions should use dotinurad with caution or avoid it, as it may be less effective or worsen existing issues. Regular monitoring of liver function tests is advised, especially for those with a history of liver disease, as other uricosuric agents have been associated with liver damage.