Clinical Pharmacokinetics and Pharmacodynamics of Cholinesterase Inhibitors
@article{Jann2002ClinicalPA, title={Clinical Pharmacokinetics and Pharmacodynamics of Cholinesterase Inhibitors}, author={Michael W. Jann and Kara Lee Shirley and Gary W. Small}, journal={Clinical Pharmacokinetics}, year={2002}, volume={41}, pages={719-739} }
Cholinesterase inhibitors are the ‘first-line’ agents in the treatment of Alzheimer’s disease. This article presents the latest information on their pharmacokinetic properties and pharmacodynamic activity.Tacrine was the first cholinesterase inhibitor approved by regulatory agencies, followed by donepezil, rivastigmine and recently galantamine. With the exception of low doses of tacrine, the cholinesterase inhibitors exhibit a linear relationship between dose and area under the plasma…
331 Citations
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References
SHOWING 1-10 OF 98 REFERENCES
Pharmacokinetic studies of cholinesterase inhibitors
- Biology, ChemistryActa neurologica Scandinavica. Supplementum
- 1993
The pharmacokinetic of some centrally acting cholinesterase inhibitors that have been used to improve memory in patients with dementia of Alzheimer's type, was compared. The original compound in this…
Clinical Pharmacokinetics of Drugs for Alzheimer’s Disease
- Biology, MedicineClinical pharmacokinetics
- 1995
The pharmacokinetics of nimodipine during multiple-dose treatment have not been studied extensively; however, the drug does not appear to accumulate during repeated administration of standard doses, and pharmacokinetic data should be determined when these methods of drug delivery are being assessed in clinical trials.
Cholinesterase Inhibitors in the Treatment of Alzheimer’s Disease
- Biology, MedicineDrug safety
- 1998
Tacrine is associated with hepatotoxicity while other cholinesterase inhibitors seem devoid this adverse effect, and concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer’s disease.
Rivastigmine, a New‐Generation Cholinesterase Inhibitor for the Treatment of Alzheimer's Disease
- Biology, MedicinePharmacotherapy
- 2000
In the two large multicenter clinical trials that used a forced‐dosage titration scheme, rivastigmine 6–12 mg/day was superior to placebo on three cognitive and functioning scales (p<0.001).
Pharmacokinetic and pharmacodynamic profile of donepezil HCl following multiple oral doses
- Medicine, Biology
- 1998
The pharmacokinetic and pharmacodynamic profile of donepezil HCl, a chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer’s disease, was characterized following administration of single oral doses to healthy volunteers.
Donepezil Use in Alzheimer Disease
- MedicineThe Annals of pharmacotherapy
- 1998
Donepezil is an effective symptomatic treatment for some patients with mild-to-moderate Alzheimer disease and appears to be a safe alternative for tacrine, given its convenient once-daily dosing, minimal adverse effects, and lower total cost.
Donepezil: an anticholinesterase inhibitor for Alzheimer's disease.
- Medicine, BiologyAmerican journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
- 1997
Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease, with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores.
Clinical Pharmacokinetics of Tacrine
- Medicine, BiologyClinical pharmacokinetics
- 1995
It has been postulated that the elevated levels of transaminase associated with tacrine therapy in vivo are dependent upon bioactivation of tacrine, mediated by hepatic CYP1A2, to form a toxic compound.
Invited Review Cholinesterase inhibitors for Alzheimer’s disease therapy: from tacrine to future applications
- Biology, MedicineNeurochemistry International
- 1998
Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition
- Biology, Medicine
- 1991
Analysis of in vitro and ex vivo concentration responses revealed no differences, indicating that no metabolites of galanthamine exert additional inhibition of acetylcholinesterase activity, and first‐order pharmacokinetics, complete oral bioavailability, were revealed.