Rivastigmine exposure provided by a transdermal patch versus capsules

• Published in: Current medical research and opinion Vol. 23; no. 12; pp. 3199 - 3204
• Main Authors: Mercier, François, Lefèvre, Gilbert, Aaron Huang, Hsun-Lun, Schmidli, Heinz, Amzal, Billy, Appel-Dingemanse, Silke
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.12.2007; Taylor & Francis; Informa Healthcare
• Subjects: Administration, Cutaneous; Aged; Aged, 80 and over; Alzheimer Disease - drug therapy; Alzheimer's disease; Capsules; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - blood; Cholinesterase Inhibitors - pharmacokinetics; Female; Humans; Male; Patch; Pharmacokinetics; Phenylcarbamates - administration & dosage; Phenylcarbamates - blood; Phenylcarbamates - pharmacokinetics; Rivastigmine; Transdermal
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/030079908X253438

ABSTRACT Objectives: The rivastigmine transdermal patch is the first transdermal treatment for Alzheimer's disease (AD) and dementia associated with Parkinson's disease. The objective of this study was to evaluate the pharmacokinetics of rivastigmine following transdermal delivery by a patch versus oral delivery with conventional capsules in a population of AD patients. Methods: Both non-compartmental and compartmental analyses were performed on the same database showing relatively large inter-patient variations in pharmacokinetic parameters (up to 73% for the capsule group). The compartmental analysis provided model-based predictions of pharmacokinetic parameters, with the aim of comparing the two modes of administration when adjusting for confounding factors such as patient body weight and gender. Results: According to both non-compartmental and compartmental analyses, the patch provided significantly lower peak rivastigmine plasma concentrations (Cmax) and slower times to Cmax (tmax), compared with capsules. However, drug exposure (area under the curve; AUC) was not significantly different between the 4.6 mg/24 hour (5 cm2) patch and 3 mg BID (6 mg/day) capsule doses, or between the 9.5 mg/24 hour (10 cm2) patch and 6 mg BID (12 mg/day) capsule doses, according to both analyses. This suggests comparable exposure from these two rivastigmine delivery systems. Conclusion: The analyses were consistent with previous reports of a markedly less fluctuating, more continuous drug delivery with the rivastigmine patch. This characteristic delivery profile is associated with similar efficacy yet improved tolerability, compared with capsules.