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

ABSTRACT

Objective: To demonstrate using pharmacokinetic (PK) modeling and simulation, that the PK parameters for drug exposure with galantamine immediate-release (IR) tablet and galantamine extended-release (ER) capsule are comparable in patients with Alzheimer's disease (AD) during the switch from twice-daily IR tablet at steady state to the new once-daily ER capsule, and to support a recommendation that patients receiving the IR tablet at steady state can be successfully switched to the ER capsule at the same daily dosage with no titration period.

Methods: Simulations were performed using a population PK model developed from clinical studies with IR galantamine in the target AD population, in combination with IR and ER absorption parameters obtained from a PK study in healthy volunteers which showed similar results. PK simulations were performed for the switch from IR tablet 8 mg b.i.d. to ER capsule 16 mg q.d. and from IR tablet 12 mg b.i.d. to ER capsule 24 mg q.d.

Results: This simulation predicted that in patients switched from the IR tablet to the ER capsule, the PK parameters for drug exposure on the first day of ER treatment would be similar to those of IR treatment at steady state. After steady state was achieved with ER galantamine, values for peak concentration and trough concentration were slightly lower (5% and 18%, respectively) than those seen at steady state for IR galantamine; this finding is considered to have no clinical implications. Area under the curve (AUC) with ER galantamine was similar to that seen at steady state with IR galantamine.

Conclusions: These results suggest that no titration period is required in patients receiving stable doses of twice-daily IR galantamine who are switched to once-daily ER galantamine. The once-daily dosage regimen of ER galantamine without a titration period should prove convenient for AD patients and their caregivers and should increase treatment compliance.

Key words: :

• Alzheimer's disease
• Galantamine
• Extended-release
• Modeling and simulation
• Pharmacokinetics