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Single- and Multiple-Dose Pharmacokinetics, Safety, and Tolerability of the Selective α7 Neuronal Nicotinic Receptor Agonist, ABT-107, in Healthy Human Volunteers

2010; Wiley; Volume: 51; Issue: 4 Linguagem: Inglês

10.1177/0091270010370460

1552-4604

Ahmed A. Othman, Robert Lenz, Jun Zhang, Jianling Li, Walid M. Awni, Sandeep Dutta,

Receptor Mechanisms and Signaling

The Journal of Clinical PharmacologyVolume 51, Issue 4 p. 512-526 Single- and Multiple-Dose Pharmacokinetics, Safety, and Tolerability of the Selective α7 Neuronal Nicotinic Receptor Agonist, ABT-107, in Healthy Human Volunteers Ahmed A. Othman PhD, Corresponding Author Ahmed A. Othman PhD Abbott Laboratories, Abbott Park, Illinois Address for correspondence: Ahmed A. Othman, PhD, Department of Clinical Pharmacokinetics and Pharmacodynamics, Abbott Laboratories, 100 Abbott Park Road, Bldg AP13A-3, Abbott Park, IL 60064; e-mail: [email protected]Search for more papers by this authorRobert A. Lenz MD, PhD, Robert A. Lenz MD, PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorJun Zhang PhD, Jun Zhang PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorJianling Li MS, Jianling Li MS Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorWalid M. Awni PhD, FCP, Walid M. Awni PhD, FCP Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorSandeep Dutta PhD, Sandeep Dutta PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this author Ahmed A. Othman PhD, Corresponding Author Ahmed A. Othman PhD Abbott Laboratories, Abbott Park, Illinois Address for correspondence: Ahmed A. Othman, PhD, Department of Clinical Pharmacokinetics and Pharmacodynamics, Abbott Laboratories, 100 Abbott Park Road, Bldg AP13A-3, Abbott Park, IL 60064; e-mail: [email protected]Search for more papers by this authorRobert A. Lenz MD, PhD, Robert A. Lenz MD, PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorJun Zhang PhD, Jun Zhang PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorJianling Li MS, Jianling Li MS Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorWalid M. Awni PhD, FCP, Walid M. Awni PhD, FCP Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this authorSandeep Dutta PhD, Sandeep Dutta PhD Abbott Laboratories, Abbott Park, IllinoisSearch for more papers by this author First published: 07 March 2013 https://doi.org/10.1177/0091270010370460Citations: 18Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract ABT-107 is a potent, selective α7 nicotinic receptor agonist under development for treatment of Alzheimer's disease and cognitive deficits associated with schizophrenia. The pharmacokinetics, safety, and tolerability of escalating single oral doses (1, 3, 10, 30, 60, 80, and 100 mg; double-blind, placebo-controlled, randomized, incomplete crossover design) and multiple oral doses (2, 6, and 15 mg once daily for 7 days; double-blind, placebo-controlled, randomized, parallel-group design) of ABT-107 were evaluated. Additionally, effect of food on ABT-107 pharmacokinetics (20-mg single dose) was evaluated using an open-label, 2-period, fasting and nonfasting, randomized, complete crossover design. ABT-107 exhibited nonlinear (more than dose-proportional) pharmacokinetics. ABT-107 half-life ranged from 7 to 10 hours, and steady state was achieved by day 6 of dosing. Food did not have a clinically meaningful effect on ABT-107 exposure. ABT-107 was safe and well tolerated over the tested dose range. The most frequently reported adverse events were nausea, headache, and tremor following single dosing and somnolence following multiple dosing. The pharmacokinetics, safety, and tolerability profiles of ABT-107 pose it as a good candidate for further development. REFERENCES 1 Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database of Systematic Reviews (Online). 2005 (3):CD003154. 2 Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database of Systematic Reviews (Online). 2006 (1):CD005593. 3 Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet. 2004; 363: 2105–2115. 4 National Institute for Health and Clinical Excellence (NICE). 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