Document Detail


Safety, Tolerability and Pharmacokinetics of the Histamine H(3) Receptor Antagonist, ABT-288, in Healthy Young Adults and Elderly Volunteers.
MedLine Citation:
PMID:  23016924     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM: The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H(3) receptor antagonist, in healthy young adults and elderly subjects following single- and multiple-dosing in Phase 1 setting. METHODS: Single-doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple-doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple-doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. Effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open-label, randomized, cross-over design. RESULTS: ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single-doses up to 40 mg and multiple-doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse-events were hot-flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 hours across dose groups. Steady state was achieved by Day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. CONCLUSIONS: Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to Phase 2 evaluation in Alzheimer's patients.
Authors:
Ahmed A Othman; George Haig; Hana Florian; Charles Locke; Jun Zhang; Sandeep Dutta
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-28
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  -     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
Affiliation:
Abbott Clinical Pharmacology and Pharmacometrics, Abbott Laboratories, Abbott Park, IL, USA; Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
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