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OBJECTIVE Our objective was to evaluate the pharmacokinetics of the Alzheimer's disease treatment memantine in subjects with normal and impaired renal function. METHODS This was a single-center, single-dose, open-label study. Thirty-two subjects aged 18 to 80 years were assigned to 1 of 4 groups (8 subjects each) based on baseline creatinine clearance:(More)
Escitalopram is the (S)-enantiomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram. Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Following oral administration, escitalopram is rapidly absorbed and reaches maximum plasma concentrations in(More)
Internal tandem duplication mutations of FLT3 (FLT3/ITD mutations) are common in acute myeloid leukemia (AML) and confer a poor prognosis. This would suggest that FLT3 is an ideal therapeutic target, but FLT3 targeted therapy has produced only modest benefits in clinical trials. Due to technical obstacles, the assessment of target inhibition in patients(More)
The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite, S-demethylcitalopram (S-DCT), were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion of escitalopram, the mean systemic clearance and volume of distribution were 31 L/h and 1,100 L, respectively. After oral administration of(More)
BACKGROUND Memantine, a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist, was approved in the US for treatment of moderate to severe Alzheimer's disease in October 2003. OBJECTIVE To determine whether an in vivo pharmacokinetic interaction exists between memantine and the acetylcholinesterase (AChE) inhibitor donepezil. (More)
BACKGROUND The high prevalence rates of both Alzheimer's disease (AD) and type 2 diabetes mellitus in the elderly population suggest that concomitant pharmacotherapy is likely. Given the renal tubular transport and extensive urinary excretion of memantine and metformin, it was of interest to assess the pharmacokinetic and pharmacodynamic interaction with(More)
The effect of steady-state istradefylline, an agent for Parkinson's disease with P-glycoprotein and CYP3A inhibitory activity, on the pharmacokinetics of atorvastatin and its metabolites was evaluated in healthy volunteers. A single 40-mg dose of atorvastatin was administered to 20 subjects. After a 4-day washout, subjects received a single 40-mg(More)
This model-based analysis quantifies the population pharmacokinetics (PK) of orally administered istradefylline, a selective adenosine A(2A) receptor antagonist, in healthy subjects and patients with Parkinson's disease, including the estimation of covariate effects on istradefylline PK parameters. Istradefylline plasma concentration data from 8 phase 1 and(More)
This model-based analysis quantifies the population pharmacokinetic-pharmacodynamic efficacy and safety/tolerability relationships of orally administered istradefylline, a selective adenosine A(2A) receptor antagonist, in healthy participants and patients with Parkinson disease. Data from 6 phase 2/3 clinical trials comprised the population database, with(More)