A Review of Clinical Pharmacokinetics and Pharmacodynamics of Galantamine, a Reversible Acetylcholinesterase Inhibitor for the Treatment of Alzheimer s Disease, in Healthy Subjects and Patients

Fenglei      Huang; Yali      Fu

Abstract

Galantamine is a reversible acetylcholinesterase inhibitor for the treatment of Alzheimer s disease. Following oral administration, galantamine is rapidly absorbed and reaches Cmax in approximately one hour for immediate release (IR) tablets and four hours for extended-release (ER) capsules. Food has no clinically important effects on the absorption of galantamine. Galantamine displays dose-proportional pharmacokinetics over a dose range of 8 - 32 mg and 8 - 24 mg for IR and ER formulations, respectively. The elimination half-life of galantamine is about 7 - 8 hours. Galantamine has low protein binding (28.3 - 33.8%) and has an apparent steady-state volume of distribution (Vss) of 193 L. Approximately 20-25% of the galantamine dose administered is excreted unchanged in urine. No clinically significant effects of age, gender, and race have been observed on galantamine pharmacokinetics. The exposures to galantamine in patients with moderate and severe renal impairment are 37% and 67% higher, respectively than in healthy subjects, whereas the exposure to galantamine is approximately 30% higher in patients with moderate hepatic impairment. Co-administration of galantamine with ketoconazole (CYP 3A4 strong inhibitor) or paroxetine (CYP 2D6 strong inhibitor) leads to a 30% and 40% increase, respectively, in galantamine exposure compared to galantamine given alone.

Keywords: Galantamine, Alzheimer's disease, drug-drug interaction, pharmacokinetics, pharmacodyanmics, acetylcholinesterase inhibitor