A study of once-a-week donepezil transdermal system's bioequivalence to oral donepezil in healthy volunteers: a plain language summary.

Abstract

This is a plain language summary of an article published in the Journal of Alzheimer's Disease. It describes an adhesive patch placed on the skin's surface, also referred to as a transdermal delivery system (or TDS), that delivers donepezil (called donepezil TDS going forward) through the skin of patients with mild, moderate, and severe dementia of the Alzheimer's type. This summary focuses on how fast and how much of the medication donepezil enters the body through the skin, and how it compares with taking a pill form of donepezil by mouth (oral donepezil). This summary also looks at how much donepezil is circulating through the body with the use of the once-a-week donepezil TDS versus the once-a-day donepezil pill. We show that the same amount of donepezil circulates through the body when donepezil TDS is used once a week as when a participant takes an oral donepezil pill once a day. Dementia is a term used to describe a person's decreasing ability to remember, think, or make decisions necessary to successfully complete daily activities. Alzheimer's disease is a disorder that progresses slowly, with the symptoms of dementia getting worse over many years. When viewed under a microscope, the visible features of Alzheimer's disease within the brain are protein deposits called plaques between brain cells and protein strands within brain cells that appear as tangles. One of the many features that cannot be seen with the naked eye in the Alzheimer's brain is the low level of a chemical called acetylcholine that allows certain nerve cells in the brain involved with memory to communicate with one another. Donepezil, a drug that is widely used to treat dementia associated with Alzheimer's disease, increases the amount of acetylcholine in the brain. Donepezil is usually in pill form and taken by mouth. However, one problem with taking oral donepezil is that it can cause stomach or intestinal side effects like diarrhea, nausea, and vomiting. These side effects may be bad enough that people stop taking their medication. In 2022, for the first time, the United States Food and Drug Administration approved a donepezil TDS marketed under the name Adlarity. Donepezil TDS is for use in patients who have mild, moderate, and severe dementia caused by Alzheimer's disease. It is applied once a week to skin on the patient's back, upper buttocks, or thigh. Donepezil TDS allows the drug donepezil to be absorbed into the body directly through the skin, which means that the drug does not go through the digestive system. This means that many stomach and intestinal side effects (the undesirable effects of the drug) can potentially be reduced. In healthy volunteers, we showed that donepezil TDS allows a similar amount of the drug into the body as the oral donepezil pill. This is done using a type of examination known as pharmacokinetics (how much, how fast, and how steadily donepezil is taken into the bloodstream). In healthy participants, donepezil TDS had overall fewer stomach and intestinal side effects (like constipation, diarrhea, nausea, and vomiting) than the oral donepezil pill, although more participants reported abdominal pain with donepezil TDS than with oral donepezil. Donepezil TDS also had fewer instances of nervous system side effects (like dizziness and sleepiness) than the oral donepezil pill. These findings support using donepezil TDS to treat patients with Alzheimer's disease.