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

Abstract

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.

Memantine: A Therapeutic Approach in Treating Alzheimers and Vascular Dementia

“…Urine acidification increases renal excretion of memantine [76]. As metabolism and hepatic clearance contribute to a minor degree to memantine elimination, metabolic drug interactions would not be anticipated.…”

Update on the use of memantine in Alzheimer’s disease

“…Since renal function may decline as result of newly prescribed medication (eg, non-steroid anti-inflammatory drugs, diuretics, ACE inhibition), side effects of memantine may develop in patients who have used memantine for some period. The pharmacokinetics of memantine can be significantly affected by high or low urine pH values 16. Alkaline urine pH results in reduced renal excretion and renal clearance, while acidic urine pH may result in increased renal clearance of memantine.…”

Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers

“…Finally, memantine was selected for the assessment of active tubular secretion, as the renal clearance of memantine at acidic pH exceeds the expected glomerular filtration rate (Freudenthaler et al 1998). However, (1) lack of published modulators for evaluation of the sensitivity and specificity of this probe, (2) low inter-individual variability observed in this study, and (3) recent findings on the influence of the glomerular filtration rate and gender as well as NR1I2 (c.1663T[C, rs1523130) polymorphism on memantine clearance (Noetzli et al 2013) preclude meaningful use of this probe in the future.…”

“…The CIME combination was therefore designed to study the pooled activity of OATP1B1 & 1B3, the pooled activity of UGT 1A1, 1A6, 1A9 & 2B15, and the activity of P-glycoprotein and of CYP2C8, by the addition of rosuvastatin, acetaminophen (acetaminophen glucuronide), digoxin and repaglinide (M4-hydroxy-repaglinide), respectively, to a widely used more conventional cocktail composed of caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A) (Tomalik-Scharte et al 2010;Wohlfarth et al 2012;Doroshyenko et al 2013). Finally, we added memantine to the CIME combination to study the renal excretion of drugs (active tubular secretion), since the plasma pharmacokinetics of memantine correlates with urine pH and memantine is not metabolized (Freudenthaler et al 1998). After development and validation of a simultaneous LC-MS/MS bioanalytical assay for the substrates of the CIME combination and main relevant metabolites (Videau et al 2010), the CIME combination was used as an index of blood-brain barrier permeation in an in vitro model (Lacombe et al 2011), to demonstrate the drug-metabolizing capacity of a microfluidic biochip containing primary human hepatocyte cultures (Prot et al 2011), and to phenotype several CYP activities in rat (Videau et al 2012).…”