Abstract | OBJECTIVE: 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.
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Authors | S Asthana, N H Greig, H W Holloway, K C Raffaele, A Berardi, M B Schapiro, S I Rapoport, T T Soncrant |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 60
Issue 3
Pg. 276-82
(Sep 1996)
ISSN: 0009-9236 [Print] United States |
PMID | 8841150
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Muscarinic Agonists
- Nicotinic Agonists
- Arecoline
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Topics |
- Aged
- Aged, 80 and over
- Alzheimer Disease
(blood, drug therapy, psychology)
- Arecoline
(administration & dosage, blood, pharmacokinetics)
- Cross-Over Studies
- Double-Blind Method
- Drug Administration Schedule
- Female
- Humans
- Infusions, Intravenous
- Male
- Memory
(drug effects)
- Middle Aged
- Muscarinic Agonists
(administration & dosage, blood, pharmacokinetics)
- Nicotinic Agonists
(administration & dosage, blood, pharmacokinetics)
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