Influence of urine pH and urinary flow on the renal excretion of memantine

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Abstract
Aims The present study assessed the influence of urinary flow rate and urine pH on the renal excretion of the NMDA-receptor antagonist memantine. Methods In a randomized, open, four-period cross-over trial, 12 healthy male volunteers received 10 mg memantine daily for 43 days. After reaching steady state conditions the volunteers were allocated to four different regimens to alter urine pH and urinary flow, which were each separated by a 1 week period while the study medication continued (A: acidification of urine pH, low urinary flow; B: acidification of urine pH, high urinary flow; C: alkalinization of urine pH, low urinary flow; D: alkalinization of urine pH, high urinary flow). Results The renal clearance of memantine (CLR ) in regimen A and B was 7–10 fold higher in comparison with regimen C and D (PR between the two regimens with acidic urine pH (A: median: 210.2 ml min−1vs B: median: 218.7 ml min−1 ) and between the two regimens with alkaline urine pH (C: median: 19.4 ml min−1vs D: median: 30.5 ml min−1 ). The amount of memantine excreted into the urine within one regimen (Ae0–24 h ) was 5.7–7.4 fold higher in regimens A and B than C and D (Pmax/AUC(0,24 h) were significant (P D. Conclusions The present study demonstrated a considerable effect of urine pH, whereas no clinically relevant change of the renal excretion of memantine with urinary flow could be detected. As the renal excretion of memantine may have an impact on therapeutic efficacy changes of dietary habits that may alter urine pH should be avoided during treatment with memantine.