title: Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats.
abstract: Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple- or single-dose oral and transdermal administration. Venous blood was collected at preset intervals in single- and multiple-dose studies. Non-compartmental pharmacokinetics was analysed for all formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and 8.21 ± 0.89 mg/kg, respectively. The maximum plasma concentration was lower and the half-life longer after patch administration than oral and IV administration. Memantine bioavailability was 41 and 63% for oral and patch administration, respectively. Steady state was achieved around 24 hr for oral and patch administration. The mean AUC increased after oral or patch administration from single to multiple dose. The memantine patch formulation displayed a longer duration of action and lower peak plasma concentration. However, drug exposure was similar to the oral formulation at each dose. Additionally, the memantine patch formulation displayed a smaller interindividual variability and lower accumulation than the oral formulation.
authors: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors: Soo-Han
authors: SH
authors: Lee
authors: Department of Veterinary Surgery, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors: Seung-Hyun
authors: SH
authors: Kim
authors: Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
authors: Yook-Hwan
authors: YH
authors: Noh
authors: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Byung-Moon
authors: BM
authors: Choi
authors: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Gyu-Jeong
authors: GJ
authors: Noh
authors: Department of Veterinary Nurse and Pet Science, Seojeong College, Yangju, Korea.
authors: Woo-Dae
authors: WD
authors: Park
authors: Pharmaceutical Research Center, Handok Incorporation, Seoul, Korea.
authors: Eun-Jung
authors: EJ
authors: Kim
authors: Department of Convergence Medical Science, Kyunghee University, Seoul, Korea.
authors: Ik-Hyun
authors: IH
authors: Cho
authors: Department of Veterinary Surgery, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors: Chun-Sik
authors: CS
authors: Bae
mesh_terms: D000279:Administration, Cutaneous; D061605:Administration, Intravenous; D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008559:Memantine / Q000008:administration & dosage / Q000493:pharmacokinetics; D018697:Nootropic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D057968:Transdermal Patch
chemical_list: D018697:Nootropic Agents; D008559:Memantine