Name: Azetukalner (XEN1101) in Focal onset seizures: Pharmacokinetics
Published: 2026-09-21T21:41:53-04:00

Product information and disease description Product description Product information Pharmacology

Pharmacokinetics

6 evidence topics · 5 sources

Absorption and time to peak concentration

“After single doses ranging from 5 to 30 mg (immediate-release capsules) administered in the fasting state, peak plasma azetukalner concentrations are achieved at 3.2–4.5 h on average. Thereafter, the drug concentration declines with a biphasic profile. Azetukalner AUC increases about 1.8-fold after co-administration with food” (opens the source at this quote in a new tab)

Food effect and dose proportionality

“Absorption in the fed state was relatively slow, with peak drug concentrations occurring at 4–6 h after dosing. When azetukalner is administered in the fasting state, exposure is less than dose proportional. However, after 10 days of once-daily (q.d.) dosing with food, exposure increases proportionally with dose” (opens the source at this quote in a new tab)

Half-life and steady state

“The half-life of azetukalner is about 1–2 days, which implies a modest (about 25%) peak-to-trough fluctuation in serum drug concentration on a q.d. dosing schedule” (opens the source at this quote in a new tab)
“After multiple dosing, azetukalner elimination shows a late terminal phase with an average half-life of 4–10 days” (opens the source at this quote in a new tab)
“Steady state (defined as no statistical difference between trough levels on successive days) is reached after 7–10 days, even though complete steady state is expected to occur after about 3 weeks” (opens the source at this quote in a new tab)

Terminal half-life supporting once-daily dosing without titration

“The pharmacokinetic properties of XEN1101, including a long terminal elimination half-life (approximately 10 days), support once-daily oral dosing without the need for titration at initiation of dosing or tapering at termination of dosing.” (opens the source at this quote in a new tab)

Phase 1 single- and multiple-ascending-dose results

“Single- and multiple-ascending-dose studies were conducted in healthy volunteers to evaluate PK and tolerability, including an evaluation of food effects. Testing included single doses of 5 mg, 15 mg, 20 mg, and 30 mg, as well as multiple doses of 15 mg once daily for 7 days. Key PK findings revealed peak plasma concentrations (Cmax) of 31.5 ng/mL (20 mg) and 35.5 ng/mL (30 mg), with corresponding half-lives of 41 h and 63.4 h. Elimination followed a biphasic pattern, characterized by a functional half-life of 1–2 days and a terminal half-life exceeding 5 days.” (opens the source at this quote in a new tab)

Metabolism and elimination

“After 10 days of dosing at 25 mg q.d., only 0.01% of the administered dose is excreted in urine as unchanged drug over a 24 h collection period, indicating that azetukalner renal clearance is negligible” (opens the source at this quote in a new tab)
“Azetukalner is cleared by CYP3A4-mediated metabolism, with other CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6) playing little or no role” (opens the source at this quote in a new tab)
“A major oxidative metabolite detected in plasma at concentrations of approximately 20% of those of the parent drug has been found to be inactive on Kv7 channels after preliminary testing” (opens the source at this quote in a new tab)