Pharmacokinetic study of memantine in healthy and renally impaired subjects.
OBJECTIVE
Our objective was to evaluate the pharmacokinetics of the Alzheimer's disease treatment memantine in subjects with normal and impaired renal function.


METHODS
This was a single-center, single-dose, open-label study. Thirty-two subjects aged 18 to 80 years were assigned to 1 of 4 groups (8 subjects each) based on baseline creatinine clearance: normal renal function (>80 mL/min), mild renal impairment (50-80 mL/min), moderate renal impairment (30-49 mL/min), and severe renal impairment (5-29 mL/min). A single 20-mg memantine dose was administered under fasting conditions. Assessments included pharmacokinetic and safety measures.


RESULTS
Thirty-one subjects completed the study. There were no relevant differences in maximum memantine plasma concentration between subjects with normal and impaired renal function of any severity. The mean area under the plasma concentration versus time curve extrapolated to infinity was similar between subjects with normal and mildly impaired renal function but increased by 60% (95% confidence interval [CI], 24%-97%) and 115% (95% CI, 77%-152%) in subjects with moderate and severe renal impairment, respectively. Simulations predicted steady-state maximum concentration values of 82 ng/mL (95% CI, 70-95 ng/mL), 85 ng/mL (95% CI, 70-101 ng/mL), and 128 ng/mL (95% CI, 109-147 ng/mL) in healthy subjects, those with mild renal impairment, and those with moderate renal impairment, respectively, for the recommended dosing regimen of 10 mg twice daily; for subjects with severe renal impairment, a steady-state maximum concentration value of 84 ng/mL (95% CI, 68-101 ng/mL) was predicted for a dosing regimen of 5 mg twice daily.


CONCLUSIONS
On the basis of the predicted steady-state plasma concentrations with the use of the current dosing regimen of 10 mg twice daily, no dosage adjustments are needed for patients with mild or moderate renal impairment. A target dose of 5 mg twice daily is recommended in patients with severe renal impairment.
Periclou
Antonia
A
Forest Research Institute, Jersey City, NJ, USA. Antonia.Periclou@frx.com
Ventura
Daniel
D
Rao
Niranjan
N
Abramowitz
Wattanaporn
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged
D015259:Dopamine Agents; D003404:Creatinine; D008559:Memantine