Clinical Pharmacokinetics and Pharmacodynamics of Cholinesterase Inhibitors

  title={Clinical Pharmacokinetics and Pharmacodynamics of Cholinesterase Inhibitors},
  author={Michael W. Jann and Kara Lee Shirley and Gary W. Small},
  journal={Clinical Pharmacokinetics},
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… 

Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Aspects of Drugs Used in the Treatment of Alzheimer’s Disease

The aim of this review is to summarize the pharmacodynamics and pharmacokinetics of the four commonly used anti-dementia drugs and to give an overview on the current knowledge of pharmacogenetics in this field.

Clinically Significant Drug Interactions with Cholinesterase Inhibitors

A review of the literature does not reveal any alarming data but does highlight the need for prudent prescription, particularly when cholinesterase inhibitors are given in combination with psychotropics or antiarrhythmics.

Pharmacokinetic rationale for the rivastigmine patch

The potential of a patch to improve the tolerability of rivastigmine while permitting similar exposure to the highest doses of capsules may, in turn, lead to improved efficacy and compliance.

Pharmacogenetic considerations when prescribing cholinesterase inhibitors for the treatment of Alzheimer’s disease

  • R. Cacabelos
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2020
The most relevant genes influencing AChEI efficacy and safety are APOE and CYPs, and APOE-4 carriers are the worst responders to A ChEIs.

Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats

Greater age effects in both pharmacokinetics and pharmacodynamics of donepezil and tacrine were seen in previous studies with Fischer 344 rats, indicating a potential risk in overreliance on this rat strain for aging studies.

Donepezil: a review

  • B. Seltzer
  • Medicine, Biology
    Expert opinion on drug metabolism & toxicology
  • 2005
Although donepezil was originally developed to inhibit the breakdown of the neurotransmitter acetylcholine as symptomatic therapy for AD, recent studies raise the possibility of other effects this drug has on the pathogenesis of AD.

Is Combining an Anticholinergic with a Cholinesterase Inhibitor a Good Strategy for High-Level CNS Cholinesterase Inhibition?

  • D. Moss
  • Biology
    Journal of Alzheimer's disease : JAD
  • 2019
The co-administration of an anticholinergic with an AChE inhibitor is a rational strategy for improving efficacy in the symptomatic treatment of dementia, but there are significant long-term risks that have not yet been considered.

The Inhibitory Effect of Rivastigmine and Galantamine on Choline Transport in Brain Capillary Endothelial Cells

The BBB choline transporter may be involved in a part of the influx and efflux transport of rivastigmine across the BBB, and should be therapeutically relevant to the treatment of Alzheimer's disease (AD) with AChE inhibitors, and, more generally, to theBBB transport of CNS-acting cationic drugs via choline transport system.

BCHE and CYP2D6 genetic variation in Alzheimer’s disease patients treated with cholinesterase inhibitors

Individualized therapy based on CYP2D6 and BCHE genotypes is unlikely to be beneficial for treating Alzheimer’s disease patients in routine clinical practice.



Pharmacokinetic studies of cholinesterase inhibitors

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

  • L. Parnetti
  • Biology, Medicine
    Clinical 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

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

  • M. Jann
  • Biology, Medicine
  • 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

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

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.

  • E. ShintaniK. M. Uchida
  • Medicine, Biology
    American 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

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.

Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition

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.