Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Effect of Renal Impairment on the Pharmacokinetics of Memantine
Takashi MoritoyoTomoko HasunumaKazuhiro HaradaTomonori TateishiMakoto WatanabeTsutomu KotegawaMasahiro NagaiYuji KumagaiTomomichi FujitaniTakahumi OkuraTomikazu FukuokaKenichi MiyoshiBunzo MatsuuraShinya FurukawaTomoe KoboriHiroyoko MoritoyoNoriko NishikawaTomoaki TsujiiHirotaka IwakiMasahiko NakamuraSatoshi MakinoKei OhnumaKoichiro YujiMegumi HashimotoMasaru TakasuYutaka HashizumeKoji YouTomoko MatsumuraYuji TanakaNahoko MatsumotoJunichi NakamuraJun MiuraTadao AkizawaKozo KitazawaTakanori ShibataAki KurokiHirokazu HondaMasanori MukaiKyoichi OhashiTakuya MorimotoHiromitsu ImaiToshiaki OkudairaFuminori SatoJunko ImanagaKatsuhiro TanakaMasahiro Nomoto
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2012 Volume 119 Issue 4 Pages 324-329

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Abstract

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.

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© 2012 The Japanese Pharmacological Society
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