Pharmacokinetic simulation for switching from galantamine immediate-release to extended-release formulation

Area of Science:

• Pharmacokinetics
• Pharmacology
• Alzheimer's Disease Therapeutics

Background:

• Galantamine is used to treat Alzheimer's disease (AD).
• Switching between immediate-release (IR) and extended-release (ER) formulations requires careful consideration of drug exposure.
• Optimizing dosing regimens can improve patient compliance and convenience.

Purpose of the Study:

• To confirm comparable pharmacokinetic (PK) parameters between galantamine IR tablets and ER capsules in AD patients.
• To support a switch from twice-daily IR galantamine to once-daily ER galantamine without a titration period.
• To evaluate the PK of galantamine during the transition from IR to ER formulations.

Main Methods:

• Population PK modeling was utilized, incorporating data from clinical studies of IR galantamine in AD patients.
• Absorption parameters from a PK study in healthy volunteers comparing IR and ER formulations were integrated.
• Simulations were conducted for dose transitions: 8 mg IR b.i.d. to 16 mg ER q.d. and 12 mg IR b.i.d. to 24 mg ER q.d.

Main Results:

• PK simulations predicted similar drug exposure on the first day of ER galantamine treatment compared to steady-state IR treatment.
• Steady-state peak and trough concentrations with ER galantamine were slightly lower (5% and 18%) than with IR galantamine, with no clinical significance.
• Area under the curve (AUC) for ER galantamine was comparable to that of steady-state IR galantamine.

Conclusions:

• No titration period is necessary when switching AD patients from stable doses of twice-daily IR galantamine to once-daily ER galantamine.
• A once-daily ER galantamine regimen simplifies treatment for AD patients and caregivers.
• This simplified dosing strategy is expected to enhance treatment compliance in Alzheimer's disease management.