Austedo's Pharmacokinetic Profile Explained
Austedo (deutetrabenazine) is a medication used to treat chorea associated with Huntington's disease and tardive dyskinesia. Its pharmacokinetic (PK) profile describes how the body absorbs, distributes, metabolizes, and excretes the drug.
How is Austedo Absorbed and Distributed in the Body?
Following oral administration, Austedo is absorbed into the bloodstream. The drug is widely distributed throughout the body. The presence of deuterium in Austedo, compared to tetrabenazine, results in a slower metabolic breakdown, leading to increased and more sustained drug levels. Specifically, the ratio of VMAT2 binding to plasma concentration is higher for Austedo than for tetrabenazine [1]. This means that at any given concentration in the blood, more of Austedo is available to bind to its target in the brain [1].
How Does the Body Metabolize Austedo?
Austedo is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, specifically CYP2D6. Deuteration of tetrabenazine leads to a slower rate of metabolism, resulting in longer half-lives for its active metabolites compared to tetrabenazine [1].
When Does Austedo Reach Peak Blood Levels?
Peak plasma concentrations of Austedo and its active metabolites are typically reached within a few hours after administration. Due to its slower metabolism, Austedo's active metabolites remain in the system for a longer duration.
How Long Does Austedo Stay in the Body?
The elimination half-life of Austedo and its active metabolites is significantly longer than that of tetrabenazine. This prolonged presence in the body contributes to its efficacy and allows for less frequent dosing [1]. The deuterated form leads to an approximately 3- to 4-fold increase in plasma concentrations of its active metabolites and a longer half-life compared to tetrabenazine [1].
What are the Active Metabolites of Austedo?
Austedo is converted in the body to active metabolites that are responsible for its therapeutic effects. These metabolites are crucial for VMAT2 inhibition, which is the mechanism by which Austedo reduces involuntary movements in conditions like Huntington's disease and tardive dyskinesia.
How Does Deuteration Affect Austedo's PK?
The incorporation of deuterium atoms into the tetrabenazine molecule, creating Austedo, is a key factor in its pharmacokinetic profile. This deuteration slows down the metabolic processes that break down the drug. This leads to higher and more consistent levels of active metabolites in the bloodstream and brain, which can potentially improve efficacy and reduce the frequency of dosing compared to non-deuterated counterparts [1].
How Does Austedo's PK Compare to Tetrabenazine?
Austedo's PK profile differs significantly from that of tetrabenazine, its non-deuterated predecessor. The deuteration in Austedo results in a slower metabolic breakdown, leading to higher plasma concentrations of active metabolites and a longer half-life. This means Austedo achieves more sustained VMAT2 inhibition at lower doses compared to tetrabenazine [1].
Sources
1. DrugPatentWatch.com