Is ticagrelor a prodrug?

• Ticagrelor is not a prodrug.
• This means it does not require metabolism to be active, unlike clopidogrel and prasugrel.
• However, ticagrelor does have an active metabolite which is equally as potent and active as ticagrelor.
• Having an active metabolite increases a drug’s duration of effect. Ticagrelor is usually taken twice a day.

Ticagrelor is not a prodrug. Prodrugs are drugs that require metabolism in the body (usually via the liver) to produce an active drug. Some other antiplatelet agents, such as clopidogrel and prasugrel are prodrugs.

Although ticagrelor does not require metabolism to be active, it is still extensively metabolized. A metabolite of ticagrelor, known as AR-C124910XX is considered just as active and potent as ticagrelor itself.

This metabolite is formed when ticagrelor is metabolized through specific liver enzymes, CYP 3A4, and CYP3A5. This means that drugs that are also metabolized through these enzymes may interact with ticagrelor. Drugs that have an active and equipotent metabolite often have a longer duration of action.

What is ticagrelor?

Ticagrelor prevents platelets in your blood from sticking together to form an unwanted blood clot that could block an artery.

Platelets are tiny blood cells that clump and stick together to repair a damaged blood vessel. Ticagrelor keeps blood flowing smoothly and may also be known as an antiplatelet agent.

What is ticagrelor used for?

Ticagrelor is an oral tablet that is usually given together with aspirin to people who have had a heart attack or a condition called acute coronary syndrome (ACS), to reduce their risk of having a stroke or other heart problems.

Ticagrelor also helps reduce the rate of stent thrombosis (a blood clot forming and blocking an area near a stent).

Ticagrelor can help reduce the risk of a first heart attack or stroke in high-risk patients with coronary artery disease, the most common type of heart disease.

Ticagrelor may also be given to some people with other heart conditions who are intolerant of aspirin.

How does ticagrelor work?

Ticagrelor works in a different way to other antiplatelet agents, such as aspirin, clopidogrel, and prasugrel.

Although it still blocks a substance called ADP (adenosine-5-diphosphate) which plays a crucial role in blood clotting, it does it by reversibly binding to a receptor called P2Y12 on the platelet surface. Reversible binding means platelet activity is restored once concentrations of ticagrelor decrease below a certain level, in contrast to other antiplatelet agents such as clopidogrel and prasugrel which bind irreversibly for the life of the platelet.

Ticagrelor works more quickly than clopidogrel. Within 30 minutes, a 180mg loading dose of ticagrelor inhibited 41% of platelets. It takes almost 8 hours for clopidogrel 600mg to achieve this same effect.

Maximum platelet inhibition (88% inhibition) was reached two hours after a dose of ticagrelor. Crushing tablets and then administering them appears to hasten the time to peak concentrations.

After administration of one dose of ticagrelor, maximum platelet inhibition is achieved at two hours and lasts for another six hours (eight hours total). 24 hours after a dose of ticagrelor, platelet inhibition is still 58%. It takes 56 hours (over 2 days) for platelet inhibition to drop to 56% and 110 hours (over 4 days) for platelet inhibition to drop to 10%.