1. ¹Novartis Pharma AG, Basel, Switzerland
2. ²Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
3. ³California Clinical Trials Medical Group, Glendale, California, USA
4. ⁴Novartis PharmOps, Horsham, UK
5. ⁵Novartis Pharma SAS, Rueil-Malmaison, France

Correspondence: G Lefèvre, (gilbert.lefevre@novartis.com)

Received 20 December 2006; Accepted 11 April 2007; Published online 23 May 2007.

Abstract

A transdermal patch has been developed for the cholinesterase inhibitor rivastigmine. This study investigated the pharmacokinetics and pharmacodynamics of rivastigmine and NAP226-90, and compared drug exposure between patch and capsule administrations. This was an open-label, parallel-group study in Alzheimer's disease patients randomized to receive either capsule (1.5–6 mg Q12H, i.e., 3–12 mg/day) or patch (5–20 cm²) in ascending doses through four 14-day periods. The patch showed lower C_max (ca. 30% lower at 20 cm², 19.5 versus 29.3 ng/ml), longer t_max (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm², 345 versus 191 ngh/ml) compared with the 6 mg Q12H capsule dose, with markedly less fluctuation between peak and trough plasma levels (80% at 20 cm² versus 620% at 1.5 mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch administration, whereas two distinct peaks were seen after capsule administration. Average exposure with the 10 cm² patch was comparable to the highest capsule dose (6 mg Q12H, i.e., 12 mg/day).