Lee Soo-Han, Kim Seung-Hyun, Noh Yook-Hwan, Choi Byung-Moon, Noh Gyu-Jeong, Park Woo-Dae, Kim Eun-Jung, Cho Ik-Hyun, Bae Chun-Sik
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
Department of Veterinary Surgery, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):122-7. doi: 10.1111/bcpt.12479. Epub 2015 Sep 28.
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.
美金刚是一种用于治疗阿尔茨海默病的非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。我们研究了大鼠口服、静脉注射和贴剂给药后的美金刚药代动力学，并比较了多次或单次口服及经皮给药后的美金刚药代动力学。在单剂量和多剂量研究中，按预设时间间隔采集静脉血。对所有制剂进行非房室药代动力学分析。美金刚的口服、静脉注射和贴剂剂量分别为10 mg/kg、2 mg/kg和8.21±0.89 mg/kg。与口服和静脉注射相比，贴剂给药后血浆最大浓度较低，半衰期较长。美金刚口服和贴剂给药的生物利用度分别为41%和63%。口服和贴剂给药约24小时后达到稳态。从单剂量到多剂量，口服或贴剂给药后的平均曲线下面积增加。美金刚贴剂制剂的作用持续时间更长，血浆峰浓度更低。然而，各剂量下的药物暴露与口服制剂相似。此外，美金刚贴剂制剂的个体间变异性比口服制剂小，蓄积性也更低。
