説明
Hydrochlorothiazide may reduce renal clearance of memantine through alkalinisation of urine, as memantine elimination is pH-dependent; the clinical impact is generally minor.
機序
Memantine is a weak base; alkaline urine (caused by carbonic anhydrase inhibition-like effects of some diuretics or alkalosis) promotes ionisation in favour of the unionised form, reducing tubular reabsorption and potentially altering systemic exposure.
臨床的意義
Pharmacokinetic modelling suggests urine pH changes of 1–2 units could alter memantine AUC; clinical case reports of toxicity are absent, but routine monitoring is advisable.
対処法
No dose adjustment required; be aware that drugs causing significant urine alkalinisation could alter memantine levels in patients with renal impairment.