Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2    Pharmacodynamics
The relationship between the pharmacodynamic activity and the mechanism(s) by which eptinezumab exerts its clinical effects is unknown.

Pharmacokinetic Properties

12.3    Pharmacokinetics
Eptinezumab exhibits linear pharmacokinetics and exposure increases proportionally with doses from 100 mg to 300 mg after intravenous administration. Steady-state plasma concentration is attained after the first dose with a once every 3-month dosing schedule.


Distribution
The central volume of distribution (Vc) for eptinezumab is approximately 3.7 liters.
Metabolism & Elimination
Eptinezumab is expected to be degraded by proteolytic enzymes into small peptides and amino acids.

The apparent clearance of eptinezumab was 0.006 L/h, and the terminal elimination half-life was approximately 27 days.

Specific Populations
A population pharmacokinetic analysis assessing the effects of age, race, sex, and body weight did not suggest any clinically significant impact of these covariates on eptinezumab exposures.

Patients with Renal or Hepatic Impairment
No dedicated studies were conducted to assess the effects of renal or hepatic impairment on the pharmacokinetics of eptinezumab. However, hepatic or renal impairment is not expected to affect the pharmacokinetics of eptinezumab. A population pharmacokinetic analysis of integrated data from eptinezumab clinical studies did not reveal clinically significant impact on pharmacokinetics of patients with hepatic or renal impairment.

Drug Interaction Studies
P450 Enzymes
Eptinezumab is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Sumatriptan
The co-administration of a single dose of 300 mg eptinezumab administered as an intravenous infusion (over a period of 1 hour ± 15 min) with a single dose of 6 mg sumatriptan administered subcutaneously did not significantly influence the pharmacokinetics of eptinezumab or sumatriptan.