Name: Atebrioz (zilurgisertib) in Fibrodysplasia ossificans progressiva: Pharmacokinetics
Published: 2026-09-27T12:28:00-04:00

Steady-state exposure in patients with FOP

“In patients with FOP receiving zilurgisertib 100 mg once daily, the steady-state zilurgisertib AUC was 11980 nM·h (30.4%) and Cmax was 893 nM (35.4%). Following multiple doses, zilurgisertib exposure was slightly greater than dose-proportional at doses above 50 mg and steady-state was achieved by Day 5. Zilurgisertib exhibited a median accumulation ratio of 1.7-fold.” (opens the prescribing information at this quote)

Absorption

“Following a single dose of 100 mg zilurgisertib in healthy subjects, the median (minimum to maximum) time to peak zilurgisertib plasma concentration (Tmax) was 2.1 hours (2.0 to 4.0 hours).” (opens the prescribing information at this quote)

“Zilurgisertib was rapidly absorbed, with median time to maximum plasma drug concentration (Cmax) of 2.0–4.1 h post-dose. Zilurgisertib exposure was more than dose proportional after single and multiple doses over the dose range tested, suggesting non-linear pharmacokinetics.” (opens the source at this quote in a new tab)

Effect of food

“Administration of a single dose of 100 mg zilurgisertib with a high-fat, high-calorie meal (50% calories from fat) had no clinically meaningful effect on zilurgisertib pharmacokinetics.” (opens the prescribing information at this quote)

“No food effect was observed on zilurgisertib pharmacokinetics, with geometric mean ratio (90% confidence interval) Cmax and area under the plasma concentration–time curve values of 0.98 (0.91 to1.06) and 1.03 (0.97 to 1.10).” (opens the source at this quote in a new tab)

Distribution

“The protein binding of zilurgisertib was 62.6%. The in vitro blood-to-plasma ratio was 1.04. The geometric mean (%CV) apparent volume of distribution (Vz/F) of zilurgisertib was 694 L (35.4%) after a single dose of 100 mg zilurgisertib in patients with FOP.” (opens the prescribing information at this quote)

Elimination, metabolism, and excretion

“After a single dose of 100 mg zilurgisertib in patients with FOP, the apparent clearance (CL/F) of zilurgisertib was 17.6 L/h (28.7%) and the elimination half-life (t½) of zilurgisertib was 27.4 hours (23%).” (opens the prescribing information at this quote)
“Zilurgisertib is predominantly metabolized by CYP3A4 and to a minor extent by CYP2D6.” (opens the prescribing information at this quote)
“Following a single oral 400 mg dose of radiolabeled zilurgisertib, 49% of the dose was recovered in feces (10% unchanged) and 38.5% in urine (28% unchanged).” (opens the prescribing information at this quote)

“Plasma half-life values ranged from 22.8 to 31.4 h, supporting once-daily dosing.” (opens the source at this quote in a new tab)
“Renal excretion under fasted conditions was 16% and 27% of total drug clearance with single and multiple doses, respectively; therefore, it was not the predominant pathway for zilurgisertib elimination.” (opens the source at this quote in a new tab)

Effect of age, sex, race, and body weight

“No clinically significant differences in the systemic exposure of zilurgisertib were observed based on age (12 to 80 years), sex (67% males, 33% females), race (74% White, 15% Black/African American, 6.5% Asian, and 2.6% other) or body weight (25 to 135 kg).” (opens the prescribing information at this quote)

Saliva as a sampling matrix

“There was a strong correlation between zilurgisertib concentrations in saliva and plasma.” (opens the source at this quote in a new tab)