Pharmacokinetic rationale for the rivastigmine patch

University of California, Los Angeles, Los Ángeles, California, United States
Neurology (Impact Factor: 8.3). 08/2007; 69(4 Suppl 1):S10-3. DOI: 10.1212/01.wnl.0000281846.40390.50
Source: PubMed

ABSTRACT The dual cholinesterase inhibitor rivastigmine is approved in capsule form in many countries for the symptomatic treatment of dementia associated with Alzheimer disease (AD) and Parkinson disease (PD). All orally administered cholinesterase inhibitors are associated with central cholinergic gastrointestinal side effects, particularly during the titration phase, which are believed to be caused by a rapid increase in brain acetylcholine levels after effective inhibition of the target enzymes. A recently developed rivastigmine transdermal patch may have the potential to reduce such side effects. Pharmacokinetic studies have shown that transdermal administration of rivastigmine prolongs t(max), lowers C(max), and reduces fluctuations in plasma concentration. The 10-cm(2) rivastigmine patch provides comparable exposure (area under the curve, AUC) to the highest capsule dose (6-mg BID) and may be the target maintenance dose for most patients, delivering optimal rivastigmine exposure to produce a therapeutic effect. The potential of a patch to improve the tolerability of rivastigmine (e.g., nausea and vomiting) while permitting similar exposure to the highest doses of capsules may, in turn, lead to improved efficacy and compliance.

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    • "The recently developed rivastigmine transdermal patch represents a next generation of acetylcholinesterase treatments, and it is now available in many countries.7 By delivering the drug through the skin, directly into the bloodstream, transdermal patches avoid first-pass effects and result in reduced rates of nausea and vomiting compared with oral ChEIs.8,9 However, the different pharmacologic characteristics of the three commonly used ChEIs may influence the treatment responses of individual patients. "
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    ABSTRACT: The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs). A 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition. In total, 164 patients aged 74.7±7.52 years (mean±SD) and with 5.12±3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients. The immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study.
    Journal of Clinical Neurology 09/2011; 7(3):137-42. DOI:10.3988/jcn.2011.7.3.137 · 1.81 Impact Factor
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    ABSTRACT: Alzheimer's disease and Parkinson's disease dementia are becoming a public health issue. Given the therapeutic pitfalls in the elderly, there is a need of effective therapies. Rivastigmine, a cholinesterase inhibitor, emerges as an important agent in the symptomatic treatment of dementia. The efficacy of this drug has been shown in several studies, being now included in the guidelines for dementia management. The new matrix rivastigmine patch represents a step forward in managing the elderly patient with dementia. The IDEAL (Investigation of Transdermal Exelon in Alzheimer's disease) study demonstrates the superiority of the transdermal rivastigmine patch over capsules, proving an increased tolerability and compliance for the 9.5 mg/24 h rivastigmine patch in patients with Alzheimer's disease. The transdermal patch with rivastigmine may offer additional therapeutic benefits and may prove to be the best delivery system for this drug to treat Alzheimer's disease. The benefits of rivastigmine in dementia associated with Parkinson's disease have been shown by a smaller study, using the oral formula, but a study using rivastigmine patch is still lacking. The new technological developments in drug delivery may change our view in managing patients, improving their adherence to therapy and better results.
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