Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple‐dose administration in healthy volunteers

Tiseo,; Friedhoff,

doi:10.1046/j.1365-2125.1998.0460s1035.x

Cited by 33 publications

(15 citation statements)

References 14 publications

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“…However, according to the current US FDA guidelines, these effects were not considered Donepezil in the treatment of patients with Alzheimer's disease Drug Profile clinically significant. Although donepezil does not have a pronounced influence on the pharmacokinetic properties of digoxin, theophyline or warfarin in healthy subjects, minor alterations of theophyline, digoxin or warfarin plasma concentrations might become clinically relevant [8][9][10][11][12][13].…”

Section: Pharmacokineticsmentioning

confidence: 98%

Donepezil in the treatment of patients with Alzheimer’s disease

Tsuno¹

2009

Expert Review of Neurotherapeutics

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Alzheimer's disease (AD) is the most common cause of dementia and is characterized by an insidious onset and slow deterioration in cognition, activities of daily living (ADL), mood stability and social functioning. The cholinesterase inhibitors (ChEIs), developed based on the cholinergic hypothesis, are currently considered to be the best established treatment for AD, although the significant advances in the symptomatic pharmacotherapy of AD may be followed by disease-modification treatments. Donepezil is a mixed competitive and noncompetitive acetylcholinesterase inhibitor that shows a relative selectivity for acetylcholinesterase inhibitor compared with butyrylcholinesterase. In many clinical trials of donepezil, beneficial effects on standard measures of cognitive function, ADL and behavior have been shown in patients with mild, moderate or severe AD. Although the pharmacological and phamacokinetic profiles of the currently available ChEIs have notable differences that may affect efficacy, the clinical significance of these differences remains hypothetical in the absence of large, randomized trials that compare the ChEIs with each other.

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Section: Pharmacokineticsmentioning

confidence: 98%

Donepezil in the treatment of patients with Alzheimer’s disease

Tsuno¹

2009

Expert Review of Neurotherapeutics

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“…Furthermore, the pharmacokinetic profiles of donepezil are not altered to any clinically relevant extent when coadministered with several drugs including digoxin [55] and the P 450 inhibitors, cimetidine [56] and ketaconazole [57,58]. In addition, the pharmacokinetic and pharmacodynamic profiles of warfarin [59], theophylline [60], digoxin, cimetidine and ketoconazole are not altered by the concurrent administration of donepezil. These results suggest that the concurrent administration of these drugs in clinical practice will not require a modification in dosing.…”

Section: Tolerabilitymentioning

confidence: 95%

Clinical Profile of Donepezil in the Treatment of Alzheimer’s Disease

Doody

1999

Gerontology

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Although the underlying pathogenesis of Alzheimer’s disease (AD) is not fully understood, one of its key features is the widespread loss of central cholinergic innervation, known to be fundamental for cognitive processes. This finding led to the hypothesis that pharmacological enhancement of acetylcholine (ACh) neurotransmission may alleviate the symptoms of AD. Currently, cholinergic therapy, particularly cholinesterase (ChE) inhibition, represents the most realistic approach to the symptomatic treatment of AD. Donepezil HCl, for example, is a piperidine-based, reversible acetylcholinesterase (AChE) inhibitor, chemically distinct from other ChE inhibitors and rationally designed for the symptomatic treatment of AD. It is highly selective for centrally acting AChE, with little or no affinity for butyrylcholinesterase, present predominantly in the periphery. Phase I and II clinical trials demonstrated donepezil’s favourable pharmacokinetic, pharmacodynamic and safety profile with no requirement for dose modification in the elderly or in patients with renal or hepatic impairment. Furthermore, its long half-life supports a simple and convenient once-daily dosing regimen. Subsequent to encouraging phase II clinical trial results, two pivotal, randomized, double-blind phase III trials (of 15 and 30 weeks’ duration) demonstrated highly significant improvements in cognition and global function in mild to moderately severe AD patients treated with either 5 or 10 mg/day donepezil compared with placebo. Adverse events in the phase II and III trials, primarily cholinergic in nature, were transient and generally mild in severity and resolved during continued donepezil administration. Thus, the donepezil clinical trials programme has shown that this drug is a clinically effective and well-tolerated, once-daily treatment for the symptoms of mild to moderately severe AD.

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“…They are all safe with respect to potential drug interactions. Donepezil and galantamine are metabolized by CYP 2D6 and 3A4, though extensive drug-interaction testing suggests few clinically important interactions (38)(39)(40)(41)(42). Rivastigmine undergoes hydrolysis, making it less likely for involvement in significant drug interactions (43).…”

Section: Reviewmentioning

confidence: 99%

Cognitive Pharmacotherapy of Alzheimer's Disease and other Dementias

Herrmann

2002

Can J Psychiatry

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A lzheimer's disease (AD) and other dementias, major causes of morbidity and mortality in late life, have significant negative consequences on family caregivers and represent a huge economic burden on society. The Canadian Study of Health and Aging determined that 8% of Canadians who are age 65 years and over met criteria for dementia, with Objective: The objective of this paper is to review the randomized controlled trials (RCTs) on the pharmacotherapy of Alzheimer's disease and other dementias and to provide evidence-based recommendations for treatment of the cognitive impairment associated with these disorders.Method: A Medline search was conducted for RCTs, using the following key words: Alzheimer's disease, dementia, therapy, cholinesterase inhibitor, donepezil, rivastigmine, and galantamine. Studies were critically appraised, followed by a review of published major clinical practice guidelines. Recommendations for treatment were made based on best available evidence. Results:The pharmacotherapy of Alzheimer's disease should include the meticulous management of vascular risk factors (for example, hypertension, diabetes, cholesterol, and stroke prophylaxis) and consideration for supplementation with folate, vitamin B complex, and vitamin E. Patients should be offered at least 1 trial of a cholinesterase inhibitor, with the possibility of another trial if the first is poorly tolerated or ineffective. Patients with vascular dementia and dementia with Lewy bodies should also be offered treatment with cholinesterase inhibitors. At this time, we lack sufficient data to recommend the use of hormone replacement or antiinflammatory therapy for treatment of dementia as the primary indication. Conclusion:Reasonable evidence exists to provide recommendations for the pharmacotherapy of dementia. Treatment will likely result in modest but important benefits to patients, caregivers, and society. (Can J Psychiatry 2002;47:715-722) See page 720 for research funding and support and page 722 for author affiliations. Clinical implications· Various pharmacologic treatment options are available for dementia. · Clinicians must constantly update their knowledge of this therapeutic area, given the significant number of studies published each year. Limitations· Recommendations provided do not include nonpharmacologic treatment or management of behavioural disturbances and caregiver stress. · Important data are still missing about interventions, such as vitamin supplementation, hormone replacement, and antiinflammatory therapy. · Treatments that provide more than just modest benefits are urgently needed.

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Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple‐dose administration in healthy volunteers

Cited by 33 publications

References 14 publications

Donepezil in the treatment of patients with Alzheimer’s disease

Donepezil in the treatment of patients with Alzheimer’s disease

Clinical Profile of Donepezil in the Treatment of Alzheimer’s Disease

Cognitive Pharmacotherapy of Alzheimer's Disease and other Dementias

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