Related Experiment Video
Updated: May 29, 2026
07:02
A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
Donepezil dosing strategies: pharmacokinetic considerations
Irving H Gomolin1, Candace Smith2, Thomas M Jeitner3
1Division of Geriatric Medicine and Clinical Pharmacology, Winthrop University Hospital, Mineola, NY; Department of Medicine, Stony Brook University, Stony Brook, NY.
Journal of the American Medical Directors Association
|September 28, 2011
Summary
This study models donepezil (Aricept) plasma concentrations, finding that higher immediate-release doses may match the new sustained-release formulation. This suggests a cost-effective alternative for Alzheimer's disease treatment.
Area of Science:
- Pharmacology
- Neuroscience
- Drug Development
Background:
- Donepezil (Aricept) is a cholinesterase inhibitor for Alzheimer's disease.
- Approved formulations include 5-mg and 10-mg immediate-release (IR) tablets and a 23-mg sustained-release (SR) formulation.
- The SR formulation may offer benefits but increases adverse reactions.
Purpose of the Study:
- To model plasma concentration profiles for higher-dose IR donepezil formulations.
- To compare these profiles with the anticipated profile of the 23-mg SR formulation.
- To provide a theoretical basis for dose escalation strategies.
Main Methods:
- Pharmacokinetic modeling to derive plasma concentration profiles.
- Comparison of steady-state concentrations for various IR and SR dosing regimens.
- Analysis of potential therapeutic equivalence and cost-effectiveness.
Main Results:
- Predicted similar steady-state plasma concentrations for 10 mg twice daily IR, 20 mg once daily IR, and 23 mg once daily SR donepezil.
- Identified theoretical basis for incremental IR dose escalation.
- Suggested potential for cost-effective alternatives using generic IR formulations.
Conclusions:
- Higher dose IR donepezil regimens can achieve similar plasma concentrations to the 23-mg SR formulation.
- Incremental IR dose escalation may minimize adverse reactions.
- Generic IR formulations offer a potentially cost-effective alternative to the SR formulation for Alzheimer's treatment.
Related Concept Videos
01:01Dosage Regimens: Partial Pharmacokinetic Parameters
It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
01:15Drug Dosing: Geriatric Patients
Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
01:28Dosage Regimens: Designs and Approaches
Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
01:25Determination of Multiple Dosing Parameters: Loading and Maintenance Doses
A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...