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- W1982930764 abstract "Objective To study the pharmacokinetics and pharmacodynamics of intravenously administered arecoline in subjects with Alzheimer's disease. Methods Plasma arecoline concentrations were measured during and after high-dose (i.e., 5 mg intravenously over 30 minutes) and up to 2 weeks of continuous multiple-dose steady-state intravenous infusions of arecoline in 15 subjects with mild to moderate Alzheimer's disease. During multiple-dose infusions, the dose of arecoline was escalated from 0.5 to 40 mg/day. Psychometric tests were administered at baseline and every other dose to determine an “optimal dose” for each subject. This dose then was administered for 1 week using a randomized, placebo-controlled, double-blind, crossover design. Plasma drug concentrations were measured by GC-MS. Results The optimal dose of arecoline varied fourfold across subjects (4 mg/day, n = 6; 16 mg/day, n = 3) with mean plasma half-lives of 0.95 ± 0.54 and 9.3 ± 4.5 (SD) minutes. Clearance and volume of distribution were 13.6 ± 5.8 L/min and 205 ± 170 (SD) L, respectively. At the dose that optimized memory, the mean plasma level was 0.31 ± 0.14 (SD) ng/ml, and it predicted the optimal dose in all subjects. Conclusions Because optimal dose variation is due to differing plasma kinetics, the plasma arecoline level measured at a single infusion rate can be used to choose the optimal dose for memory enhancement in patients with Alzheimer's disease. Clinical Pharmacology & Therapeutics (1996) 60, 276–282; doi:" @default.
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- W1982930764 date "1996-09-01" @default.
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- W1982930764 title "Clinical pharmacokinetics of arecoline in subjects with Alzheimer's disease*" @default.
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- W1982930764 doi "https://doi.org/10.1016/s0009-9236(96)90054-5" @default.
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