Ein transdermales Pflaster zur Therapie der Alzheimer-Demenz

Zusammenfassung

Das transdermale Rivastigmin-Pflaster (Exelon^® Pflaster) stellt die erste, für die Alzheimer Krankheit (AD) entwickelte, transdermale Therapieform dar. Transdermale Applikationsformen, wie z. B. Pflaster sorgen für eine gleichmäßige und kontinuierliche Wirkstoffabgabe über die Haut ins Serum, senken dabei die Absorptionsrate und garantieren - verglichen mit der herkömmlichen oralen Verabreichung - einen konstanteren Plasmaspiegel. Im Falle des Rivastigmin- Pflasters kommt es hierdurch zu einer Reduktion von akuten gastrointestinalen Nebenwirkungen (wie beispielsweise Übelkeit und Erbrechen), die üblicherweise von Alzheimer- Patienten während der Einstellungsphase mit Cholinesterasehemmern berichtet werden. Dies wiederum erleichtert den Zugang zu optimalen therapeutischen Dosen, sorgt für eine bessere Compliance und hat positive Auswirkungen auf die Wirksamkeit der Therapie. Dieser Artikel bietet einen Überblick über die aus verschiedenen Studien vorliegenden Daten zum transdermalen Rivastigmin-Pflaster, das zur symptomatischen Behandlung von leichter bis mittelschwerer AD eingesetzt wird. Ferner wird der Nutzen der Pflasteranwendung gegenüber der Einnahme von Kapseln erörtert. Besonderes Augenmerk gilt dabei den Ergebnissen der richtungsweisenden IDEAL-Studie.

Summary

The rivastigmine transdermal patch (Exelon^® transdermal patch) is the first transdermal treatment developed for Alzheimer’s disease (AD). Patches provide smooth and continuous drug delivery through the skin and into the bloodstream, lowering the rate of absorption and providing steadier plasma levels versus conventional oral administration. In the case of the rivastigmine patch, this has the potential to reduce the incidence of acute gastrointestinal adverse events (such as nausea and vomiting) that are typically reported by AD patients during the titration phase of cholinesterase inhibitor treatments. This in turn may allow easier access to optimal therapeutic doses, help to improve compliance, and have a positive impact on the efficacy of treatment. This article reviews the available pharmacokinetic and clinical data from various studies of a novel rivastigmine transdermal patch for the symptomatic treatment of mild to moderate AD. We also discuss the potential benefits of patch administration over capsule administration, with a focus on the results of the landmark IDEAL trial.

Schlüsselwörter

Alzheimer Krankheit - Rivastigmin - Cholinesterasehemmer - Demenz - transdermal - Pflaster

Keywords

Alzheimer’s disease - rivastigmine - cholinesterase inhibitors - dementia - transdermal - patch

• Literatur

• 1 Fratiglioni L. et al. Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000; 54 11 Suppl 5 S10-15.
• 2 Wimo A, Jonsson L, Winblad B. An estimate of the worldwide prevalence and direct costs of dementia in 2003. Dement Geriatr Cogn Disord 2006; 21 (Suppl. 03) 175-181.
• 3 Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976; 2 8000 1403.
• 4 Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1: 55-65.
• 5 Rosler M. et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. Bmj 1999; 318 7184 633-638.
• 6 Schneider LS, Anand R, Farlow MR. Systematic review of the efficacy of rivastigmine for patients with Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1 (Suppl. 01) S26-34.
• 7 Emre M. et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 2004; 351 (Suppl. 24) 2509-2518.
• 8 Darreh-Shori T. et al. Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months. Neurology 2002; 59 (Suppl. 04) 563-572.
• 9 Giacobini E. et al. Inhibition of acetyl- and butyryl- cholinesterase in the cerebrospinal fluid of patients with Alzheimer’s disease by rivastigmine: correlation with cognitive benefit. J Neural Transm 2002; 109 7–8 1053-1065.
• 10 Hogan DB. et al. Comparison studies of cholinesterase inhibitors for Alzheimer’s disease. Lancet Neurol 2004; 3 (Suppl. 10) 622-626.
• 11 Doody RS. et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56 (Suppl. 09) 1154-1166.
• 12 Imbimbo BP. Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer’s disease. CNS Drugs 2001; 15 (Suppl. 05) 375-390.
• 13 Jann MW, Shirley KL, Small GW. Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin Pharmacokinet 2002; 41 (Suppl. 10) 719-739.
• 14 Zhao Q. et al. Pharmacokinetics of extended-release and immediate-release formulations of galantamine at steady state in healthy volunteers. Curr Med Res Opin 2005; 21: 1547-1554.
• 15 Lefevre G. et al. Pharmacokinetics of a rivastigmine transdermal patch formulation in healthy volunteers: relative effects of body site application. J Clin Pharmacol 2007; 47 (Suppl. 04) 471-478.
• 16 Nitti VW. et al. Transdermal delivery of drugs for urologic applications: basic principles and applications. Urology 2006; 67 (Suppl. 04) 657-664.
• 17 Lefèvre G. et al. Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer’s disease patients. Clin Pharm Ther. 2007 e-pub ahead of print.
• 18 Winblad B. et al. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease-- rivastigmine patch versus capsule. Int J Geriatr Psychiatry 2007; 22 (Suppl. 05) 456-467.
• 19 Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353 (Suppl. 05) 487-497.
• 20 Cramer J. Identifying and improving compliance patterns. In: Cramer J, Spilker B. eds. Patient compliance in medical practice and clinical trials. New York: Raven Press; 1991: 387-392.
• 21 Winblad B. et al. Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer’s disease. Int J Geriatr Psychiatry 2007; 22 (Suppl. 05) 485-491.