David R Guay1. 1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455, USA. guayx001@umn.edu
Abstract
OBJECTIVE: To assess the potential role of a new transdermal (TD) formulation of rivastigmine in the management of Alzheimer's disease. DATA SOURCE: MEDLINE/PUBMED and EMBASE searches (1986-February 2008) were conducted to identify pertinent English-language studies of TD rivastigmine. STUDY SELECTION AND DATA EXTRACTION: All studies evaluating any aspect of TD rivastigmine, including in vivo animal experimentation. DATA SYNTHESIS: Rivastigmine is the first acetylcholinesterase inhibitor to be marketed in a TD formulation. This formulation was marketed to potentially improve patient/caregiver adherence and ameliorate the gastrointestinal (GI) intolerance of the oral product. The TD formulation significantly reduces GI intolerance (manifested as nausea, vomiting, abdominal pain/cramping, anorexia, and weight loss) as compared with oral doses producing the same degree of systemic exposure, as a result of the lower peak plasma concentration, lower degree of peak-trough concentration fluctuation, and prolonged time to peak concentration achieved with the TD formulation. CONCLUSION: Despite the advantages of TD rivastigmine just described, a number of questions still exist with this formulation. The effects of environmental factors on drug pharmacokinetics are unknown (e.g., febrile disease states, skin abrasions/tears). The TD formulation has not eliminated the need for titration to the target dose. The true effect of this formulation on adherence is unknown (consider the dexterity necessary to access the patch from its packaging and apply it and the complexities of rotating application sites). If the patient removes the patch inappropriately, the number of available application sites falls substantially, making site rotation difficult. For patients with swallowing difficulties, oral liquid formulations of donepezil, galantamine, and rivastigmine may be easier alternatives to TD rivastigmine. Unique advantages of TD rivastigmine have not been convincingly established.
OBJECTIVE: To assess the potential role of a new transdermal (TD) formulation of rivastigmine in the management of Alzheimer's disease. DATA SOURCE: MEDLINE/PUBMED and EMBASE searches (1986-February 2008) were conducted to identify pertinent English-language studies of TD rivastigmine. STUDY SELECTION AND DATA EXTRACTION: All studies evaluating any aspect of TD rivastigmine, including in vivo animal experimentation. DATA SYNTHESIS: Rivastigmine is the first acetylcholinesterase inhibitor to be marketed in a TD formulation. This formulation was marketed to potentially improve patient/caregiver adherence and ameliorate the gastrointestinal (GI) intolerance of the oral product. The TD formulation significantly reduces GI intolerance (manifested as nausea, vomiting, abdominal pain/cramping, anorexia, and weight loss) as compared with oral doses producing the same degree of systemic exposure, as a result of the lower peak plasma concentration, lower degree of peak-trough concentration fluctuation, and prolonged time to peak concentration achieved with the TD formulation. CONCLUSION: Despite the advantages of TD rivastigmine just described, a number of questions still exist with this formulation. The effects of environmental factors on drug pharmacokinetics are unknown (e.g., febrile disease states, skin abrasions/tears). The TD formulation has not eliminated the need for titration to the target dose. The true effect of this formulation on adherence is unknown (consider the dexterity necessary to access the patch from its packaging and apply it and the complexities of rotating application sites). If the patient removes the patch inappropriately, the number of available application sites falls substantially, making site rotation difficult. For patients with swallowing difficulties, oral liquid formulations of donepezil, galantamine, and rivastigmine may be easier alternatives to TD rivastigmine. Unique advantages of TD rivastigmine have not been convincingly established.
Authors: Sherri Young; Karine Fabio; Christophe Guillon; Pramod Mohanta; Timothy A Halton; Diane E Heck; Robert A Flowers; Jeffrey D Laskin; Ned D Heindel Journal: Bioorg Med Chem Lett Date: 2010-03-03 Impact factor: 2.823