Memantine pharmacokinetics

In vitro studies have shown that memantine produces minimal inhibition of CYP450 enzymes CYP1A2, 2A6, 2C9,2D6, 2E1, and 3A4. These data indicate that no pharmacokinetic interactions with drugs metabolized by these enzymes should be expected.38... 

Pharmacokinetic and pharmacodynamic data from an open study in 24 healthy subjects suggested that there is no interaction between memantine (an N-methyl-D-aspartate receptor antagonist approved for treatment of... 

Periclou AP, Ventura D, Sherman T, Rao N, Abramowitz WT. Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother 2004 38(9) 1389-94. 

Memantine is unlikely to affect pharmacokinetics of acetylcholinesterase inhibitors... 

Noetzli M, Guidi M, Ebbing K, Eyer S, Wilhelm L, Michon A et al (2013) Population pharmacokinetic study of memantine Effects of clinical and genetic factors. Clin Pharmacokinet 52 211-223... 

Memantine. 3,S-Dimethyltricyclo[3.3.I.I3 ]decan-1-amine 3,S-dimethyl-l-adamantanamine 1 -amino-3,5-dimethyladamantane DMAA D 145. C.jH N mol wt 179.31. C 80.38%, H 11.81%, N 7.81%. Deriv of adaman-tine, q.v.. with anti-parkinson activity. Prepn of the hydrochloride K. Gerzon et al. J. Med. Chem. 6, 760 (1963) of the free base and hydrochloride J. Mills, E. Krumkalns, UJS. pat. 3,391,142 (1968 to Lilly). GC and mass spec studies of memantine metabolites W. Wesemann et al, Arznei-mittel-Forsch. 27, 1471 (1977), Effects in parkinsonian patients P. -A. Fischer er at., Ibid, 1487. Series of articles on distribution, effects on neurobiological processes, clinical studies in control of micturition and limb muscle mobility ibid. 32, 1236-1276 (1982). Clinical studies as antispasmod-ic agent H. Rohde, Fortschr. Med. 100, 2023 (1982). Pharmacodynamics and pharmacokinetics W. Wesemann et al, Arzneimittel-Forsch. 33, 1122 (1983). 

Memantine is a colorless to white crystalline substmice readily soluble in water. Its oral bioavailability is nearly 1(X)%. Memantine readily crosses the blood-brain barrier, and while in organism ii shows linear, dose-proportional pharmacokinetics and weak protein-binding properties. 

The previously mentioned clinical studies indicate that memantine and donepezil can be safely coadministered, with no significant effects on the pharmacokinetic profile... 

Memantine does not appear to attenuate the anticholinesterase effects of donepezil, galantamine, or tacrine, nor affect the pharmacokinetics of galantamine or donepezil. 

An in vitro study in rats suggested that memantine does not attenuate the anticholinesterase effects of donepezil at therapeutic concentrations. In a later study 19 healthy subjects were given memantine 10 mg before and on the last day of taking donepezil (5 mg daily for 7 days then 10 mg daily for 22 days). The pharmacokinetics of both drugs were not significantly affected by concurrent use, and the effects of donepezil on anticholinesterase were also unaffected. Furthermore, an efficacy and safety study of one year s duration has reported that the combination is well tolerated and beneficial. ... 

An in vitro study in rats suggested that memantine does not attenuate the anticholinesterase effects of galantamine at therapeutic concentrations. A study in 15 healthy subjects found that the concurrent use of extended-re-lease galantamine 16 mg daily with memantine 10 mg twice daily for 12 days did not affect the pharmacokinetics of galantamine and generally did not increase the incidence of adverse effects, although dizziness may have been more common. ... 

Yao C, Raoufinia A, Gold M, Nye J, Ramael, Padmanabhan M, Walschap Y, Verfia he T, Zhao Q. Steady-state pharmacokinetics of galantamine are not affected hy additicxi of memantine in healthy subjects. J CUn Pharmacol (2005) 45,519-28. 

The use of memantine with a combined product containing glibenclamide and metformin did not result in any changes in the pharmacokinetics of either of the three drugs. Memantine did not reduce the glucose-lowering effects of either drug. ... 

---