Effect of Renal Impairment on the Pharmacokinetics of Memantine

Journal of Pharmacological Sciences

Tadao Akizawa²  Aki Kuroki²  Tomikazu Fukuoka²  Yutaka Hashizume²  Jun Miura²  Tomoaki Tsujii²  Kei Ohnuma²  Takashi Moritoyo²  Tomonori Tateishi²  Hiromitsu Imai²  Tomoko Matsumura²  Fuminori Sato²  Tomomichi Fujitani¹  Shinya Furukawa²  Kazuhiro Harada²  Hiroyoko Moritoyo²  Masaru Takasu²  Kozo Kitazawa²  Masahiro Nomoto²  Kyoichi Ohashi²  Masahiro Nagai²  Toshiaki Okudaira²  Masahiko Nakamura²  Junko Imanaga²  Koichiro Yuji²  Tomoko Hasunuma²  Junichi Nakamura²  Takuya Morimoto²  Hirokazu Honda²  Makoto Watanabe²  Megumi Hashimoto²  Koji You²  Tomoe Kobori²  Kenichi Miyoshi²  Masanori Mukai²  Nahoko Matsumoto²  Tsutomu Kotegawa²  Bunzo Matsuura²  Takanori Shibata²  Katsuhiro Tanaka²  Takahumi Okura²  Noriko Nishikawa²  Yuji Tanaka²  Hirotaka Iwaki²  Satoshi Makino²  Yuji Kumagai² 

[1] Asubio Pharma Co., Ltd., Japan;ANTCliPh (Academic Network for Trials in Clinical Pharmacology) Trial 02 Study Group

关键词: memantine;    renal impairment;    pharmacokinetics;    dose;    dementia;   

DOI  :  10.1254/jphs.12043FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(12)Cited-By(1)The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CLCR): normal renal function (> 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7). Mean memantine maximum plasma concentration (Cmax) was similar in the groups (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to Cmax (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine determined from mean area under the plasma concentration–time curve was 1.62-, 1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal impairment, respectively, as compared to controls with normal renal function. Mean memantine plasma elimination half-life increased according to increasing renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%, respectively). These results are the same as those in the previous study on caucasian individuals, when compared per body weight. It is suggested that the dose of memantine should be halved in patients with renal impairment.

【 授权许可】

Unknown