Download PDF
Nervenheilkunde 2018; 37(04): 233-242
DOI: 10.1055/s-0038-1641240
Morbus Parkinson
Schattauer GmbH

Update Pharmakotherapie bei Parkinson

Pharmacotherapy in Parkinson’s disease
U. M. Fietzek
1   Schön Klinik München-Schwabing
,
A. O. Ceballos-Baumann
1   Schön Klinik München-Schwabing
› Author Affiliations
Further Information

Publication History

eingegangen am: 01 December 2017

angenommen am: 22 December 2017

Publication Date:
02 April 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Auch im letzten Jahr wurden zahlreiche pharmakotherapeutische Entwicklungen für die Parkinsonkrankheit vorangebracht. Die in den USA kommerziell erfolgreiche retardierte Darreichungsform von Levodopa IPX066 ist in Europa zwar zugelassen, aber nicht am Markt verfügbar. Eine speziell gefaltete Akkordeon Pille verspricht ebenso eine vereinfachte Galenik bei besserer klinischer Wirkung. Levodopa ist als Inhalativum kurz vor Markteintritt und zeigt in den vorgelegten Studien, dass Off-Phasen erfolgreich verkürzt werden können, allerdings nicht schnellere Hilfe leisten als die verfügbaren Stand-by Medikamente. Neu ist auch, dass L-Dopa über die Haut appliziert werden kann. Safinamid und Opicapon sind über Rezept verfügbar. Für letzteres liegen die Ergebnisse der Zulassungsstudien vor. Die neue AmantadinGalenik hat in den USA aufgrund günstiger Studiendaten die Zulassung zur Behandlung von Dyskinesien erhalten. Auch hat sich das Verständnis um Risikofaktoren zur Entwicklung eines Parkinson deutlich weiterentwickelt. Wir stellen neueste Arbeiten zu dem Glucagon-like-Peptid-Analogon Exenatide und dem ß2-Adrenorezeptor vor.

Summary

During the last year numerous pharmacotherapeutic developments have taken place in the field of Parkinson’s disease (PD). The commercially successful IPX066 is a levodopa formulation with controlled release that is registered in Europe but not marketed. A specially folded accordion levodopa pill promises easier use and improved clinical efficacy. Levodopa is a now available to inhale, and has shown efficacy to shorten OFF phases. However, it is not faster than available rescue preparations such as the apomorphine pen. Another novelty is the Neuroderm pump that delivers levodopa subcutaneously. Safinamide and opicapone are available by prescription. The data of the opicapone registration study is published by now. The new amantadine with controlled release has been registered for use in dyskinetic patients in the USA. Our understanding of the pathomechanisms and risk factors to develop PD has been expanded. We report the newest research concerning the glucagon-like-peptide analogue exenatide and the ß2-adrenoreceptor.

SchlüsselWörter

Parkinson - Pharmakotherapie - Levodopa - motorische Komplikationen - Schmerz - Psychose

Keywords

Parkinson’s disease - pharmacotherapy - levodopa - motor complications - pain - psychosis
 

  • Literatur

  • 1 RYTARY (carbidopa and levodopa) Extended-Release Capsules [Internet]. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/203312orig1s000toc.cfm
  • 2 Hauser RA, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M. et al. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol 2013; 12 (04) 346-56.
    CrossrefPubMedSearch in Google Scholar
  • 3 Pahwa R, Lyons KE, Hauser RA, Fahn S, Jankovic J, Pourcher E. et al. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson’s disease. Parkinsonism Relat Disord 2014; 20 (02) 142-8.
    CrossrefPubMedSearch in Google Scholar
  • 4 Stocchi F, Hsu A, Khanna S, Ellenbogen A, Mahler A, Liang G. et al. Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients. Parkinsonism Relat Disord 2014; 20 (12) 1335-40.
    CrossrefPubMedSearch in Google Scholar
  • 5 Silver DE, Trosch RM. Physicians’ experience with RYTARY (carbidopa and levodopa) extended-release capsules in patients who have Parkinson disease. Neurology 2016; 86 (14 Suppl 1): S25-35.
    CrossrefPubMedSearch in Google Scholar
  • 6 Espay AJ, Pagan FL, Walter BL, Morgan JC, Elmer LW, Waters CH. et al. Optimizing extended-release carbidopa/levodopa in Parkinson disease: Consensus on conversion from standard therapy. Neurol Clin Pract 2017; 07 (01) 86-93.
    CrossrefPubMedSearch in Google Scholar
  • 7 European Medicines Agency – Find medicine – Numient [Internet]. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002611/human_med_001934.jsp&mid=WC0b01ac058001d124.
  • 8 Verhagen LMetman, Stover N, Chen C, Cowles VE, Sweeney M. Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson’s disease. Mov Disord Off J Mov Disord Soc 2015; 30 (09) 1222-8.
    CrossrefPubMedSearch in Google Scholar
  • 9 LeWitt PA, Friedman H, Giladi N, Gurevich T, Shabtai H, Djadetti R. et al. Accordion pill carbidopa/levodopa for improved treatment of advanced Parkinson’s disease symptoms. In: Supplement 1. Dublin, Ireland; 2012; 408.
    PubMedSearch in Google Scholar
  • 10 LeWitt PA, Friedman H, Giladi N. Sustained-release carbidopalevodopa (accordian pill) in patients with advanced Parkinson’s disease: pharmacokinetic and clinical experience. In: Supplement 1. Sydney, Australia; 2013; S499.
    Search in Google Scholar
  • 11 LeWitt PA, Giladi N, Gurevich T. Accordion pill carbidopa/ levodopa (AP-CD/LD) for treatment of advanced Parkinson’s disease (PD). In: Supplement 1. Stockholm, Sweden 2014; S668.
    Search in Google Scholar
  • 12 A Study to Assess the Efficacy and Safety of the Gastric-retentive AP-CD/LD in Advanced Parkinson’s Patients – Full Text View – ClinicalTrials.gov [Internet]. https://clinicaltrials.gov/ct2/show/NCT02605434
  • 13 Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH. et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014; 13 (02) 141-9.
    CrossrefPubMedSearch in Google Scholar
  • 14 Nyholm D, Nilsson AIMRemahl, Dizdar N, Constantinescu R, Holmberg B, Jansson R. et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005; 64 (02) 216-23.
    CrossrefPubMedSearch in Google Scholar
  • 15 Senek M, Nielsen EI, Nyholm D. Levodopa-entacapone-carbidopa intestinal gel in Parkinson’s disease: A randomized crossover study. Mov Disord Off J Mov Disord Soc 2017; 32 (02) 283-6.
    CrossrefPubMedSearch in Google Scholar
  • 16 Tambasco N, Romoli M, Calabresi P. Levodopa in Parkinson’s disease: current status and future Developments. Curr Neuropharmacol. 2017 May 10; E-pub..
    PubMedSearch in Google Scholar
  • 17 LeWitt PA, Hauser RA, Grosset DG, Stocchi F, Saint-Hilaire M-H, Ellenbogen A. et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord 2016; 31 (09) 1356-65.
    CrossrefPubMedSearch in Google Scholar
  • 18 LeWitt PA, Pahwa R, Sedkov A, Corbin A, Batycky R, Murck H. Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson’s Disease. J Aerosol Med Pulm Drug Deliv. 2017 Nov 21; E-pub..
    PubMedSearch in Google Scholar
  • 19 Freitas ME, Ruiz-Lopez M, Fox SH. Novel levodopa formulations for Parkinson’s disease. CNS Drugs 2016; 30 (11) 1079-95.
    CrossrefPubMedSearch in Google Scholar
  • 20 Caraco Y, Oren S, LeWitt P. Constant therapeutic levodopa (LD) plasma concentrations maintained by continuous subcutaneous (SC) administration of ND-0612, a novel formulation of LD/carbidopa (CD). In: Supplement 1. Sydney 2013; S452.
    PubMedSearch in Google Scholar
  • 21 Yacoby-Zeevi O, LeWitt PA. Maintenance of constant steady state therapeutic plasma concentrations of levodopa following its continuous subcutaneous administration with carbidopa. In: Supplement. Dublin, Ireland 2012; S43.
    PubMedSearch in Google Scholar
  • 22 Giladi N, Caraco Y, Gurevich T, Djadetti R, Cohen Y, Yacoby-Zeevi O. et al. Pharmacokinetics and safety of ND0612L (levodopa/carbidopa for subcutaneous infusion): results from a phase II study in moderate to severe Parkinson’s disease. 2015 P1.187..
    PubMedSearch in Google Scholar
  • 23 Giladi N, Caraco Y, Gurevich T, Djadetti R, Cohen Y, Yacoby-Zeevi O. et al. Stable levodopa plasma levels with ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson’s Disease with motor fluctuations. San Diego, CA, USA; 2015: 1995
    Search in Google Scholar
  • 24 Giladi N, Caraco Y, Gurevich T, Djadetti R, Cohen Y, Yacoby-Zeevi O. et al. Pharmacokinetic profile of low-dose ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with moderate to severe Parkinson’s disease. San Diego, CA, USA; 2015: 1995
    Search in Google Scholar
  • 25 Adar L, Rachmilewitz T, Cohen Y, Oren S. Pharmacokinetic profile of continuous levodopa/carbidopa delivery when administered subcutaneously (ND0612) versus duodenal infusion (levodopa/ carbidopa intestinal gel). In Vancouver, Canada; 2017
    Search in Google Scholar
  • 26 A Clinical Study Investigating the Efficacy, Tolerability, and Safety of Continuous Subcutaneous ND0612 Infusion Given as Adjunct Treatment to Oral Levodopa in Patients With Parkinson’s Disease With Motor Fluctuations – Full Text View – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02782481
  • 27 Bredenberg S, Nyholm D, Aquilonius SM, Nyström C. An automatic dose dispenser for microtablets – a new concept for individual dosage of drugs in tablet form. Int J Pharm 2003; 261 (1–2): 137-46.
    CrossrefPubMedSearch in Google Scholar
  • 28 Senek M, Hellström M, Albo J, Svenningsson P, Nyholm D. First clinical experience with levodopa/carbidopa microtablets in Parkinson’s disease. Acta Neurol Scand 2017; 136 (06) 727-31.
    CrossrefPubMedSearch in Google Scholar
  • 29 Senek M, Aquilonius S-M, Askmark H, Bergquist F, Constantinescu R, Ericsson A. et al. Levodopa/ carbidopa microtablets in Parkinson’s disease: a study of pharmacokinetics and blinded motor assessment. Eur J Clin Pharmacol 2017; 73 (05) 563-71.
    CrossrefPubMedSearch in Google Scholar
  • 30 Stocchi F, Arnold G, Onofrj M, Kwiecinski H, Szczudlik A, Thomas A. et al. Improvement of motor function in early Parkinson disease by safinamide. Neurology 2004; 63 (04) 746-8.
    CrossrefPubMedSearch in Google Scholar
  • 31 Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D. et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord Off J Mov Disord Soc 2014; 29 (02) 229-37.
    CrossrefPubMedSearch in Google Scholar
  • 32 Cattaneo C, Sardina M, Bonizzoni E. Safinamide as Add-On Therapy to Levodopa in Midto LateStage Parkinson’s Disease Fluctuating Patients: Post hoc Analyses of Studies 016 and SETTLE. J Park Dis 2016; 06 (01) 165-73.
    Search in Google Scholar
  • 33 Kaakkola S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson’s disease. Int Rev Neurobiol 2010; 95: 207-25.
    PubMedSearch in Google Scholar
  • 34 Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha J-F, McCrory M. et al. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol 2017; 74 (02) 197-206.
    CrossrefPubMedSearch in Google Scholar
  • 35 Ferreira JJ, Lees A, Rocha J-F, Poewe W, Rascol O, Soares-da-Silva P. et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol 2016; 15 (02) 154-65.
    CrossrefPubMedSearch in Google Scholar
  • 36 Schwab RS, England AC, Poskanzer DC, Young RR. Amantadine in the treatment of Parkinson’s disease. JAMA 1969; 208 (07) 1168-70.
    CrossrefPubMedSearch in Google Scholar
  • 37 Amantadine and other antiglutamate agents: management of Parkinson’s disease. Mov Disord Off J Mov Disord Soc 2002; 17 (Suppl. 04) S13-22.
    CrossrefPubMedSearch in Google Scholar
  • 38 Verhagen LMetman, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 1998; 50 (05) 1323-6.
    CrossrefPubMedSearch in Google Scholar
  • 39 Pahwa R, Tanner CM, Hauser RA, Sethi K, Isaacson S, Truong D. et al. Amantadine extended release for levodopa-induced dyskinesia in Parkinson’s disease (EASED Study). Mov Disord Off J Mov Disord Soc 2015; 30 (06) 788-95.
    CrossrefPubMedSearch in Google Scholar
  • 40 Oertel W, Eggert K, Pahwa R, Tanner CM, Hauser RA, Trenkwalder C. et al. Randomized, placebocontrolled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson’s disease (EASE LID 3). Mov Disord Off J Mov Disord Soc. 2017 Aug 21; E-pub..
    PubMedSearch in Google Scholar
  • 41 Court E. Adamas Pharma says its new Parkinson’s drug isn’t just a more expensive, long-acting version of generic [Internet]. MarketWatch. http://www.marketwatch.com/story/adamas-pharma-says-its-new-parkinsons-drug-isnt-just-a-more-expensive-long-acting-version-ofgeneric-2017–08–29.
  • 42 Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson’s disease (NOH306A). J Park Dis 2014; 04 (01) 57-65.
    Search in Google Scholar
  • 43 Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson’s disease (nOH306B). Mov Disord Off J Mov Disord Soc 2015; 30 (05) 646-54.
    CrossrefPubMedSearch in Google Scholar
  • 44 Hauser RA, Heritier S, Rowse GJ, Hewitt LA, Isaacson SH. Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension. Clin Neuropharmacol 2016; 39 (05) 220-6.
    CrossrefPubMedSearch in Google Scholar
  • 45 François C, Rowse GJ, Hewitt LA, Vo P, Hauser RA. Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension. BMC Neurol 2016; 16 (01) 143.
    CrossrefPubMedSearch in Google Scholar
  • 46 Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M. et al. Caffeine for treatment of Parkinson disease: a randomized controlled trial. Neurology 2012; 79 (07) 651-8.
    CrossrefPubMedSearch in Google Scholar
  • 47 Postuma RB, Anang J, Pelletier A, Joseph L, Moscovich M, Grimes D. et al. Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial. Neurology 2017; 89 (17) 1795-803.
    CrossrefPubMedSearch in Google Scholar
  • 48 Ellis JM, Fell MJ. Current approaches to the treatment of Parkinson’s Disease. Bioorg Med Chem Lett 2017; 27 (18) 4247-55.
    CrossrefPubMedSearch in Google Scholar
  • 49 Clinical Results Presented from Prothena’s Phase 1b Study of PRX002/RG7935 Demonstrating Robust Antibody CNS Penetration and Significant Reduction of Free Serum Alpha-synuclein in Patients with Parkinson’s Disease. http://ir.prothena.com//releasedetail.cfm?releaseid=1019672.
  • 50 Human-derived α-synuclein antibody BIIB054 binds pathologic forms of α-synuclein and attenuates transmission of α-synuclein in vitro and in vivo [Internet]. MDS Abstracts. http://www.mdsabstracts.org/abstract/human-derived-synuclein-antibodybiib054-binds-pathologic-forms-of-synuclein-andattenuates-transmission-of-synuclein-in-vitro-andin-vivo/.
  • 51 Hölscher C. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol 2014; Apr; 221 (01) T31-41.
    CrossrefPubMedSearch in Google Scholar
  • 52 Hölscher C. Potential role of glucagon-like peptide-1 (GLP-1) in neuroprotection. CNS Drugs 2012; 26 (10) 871-82.
    CrossrefPubMedSearch in Google Scholar
  • 53 Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T. et al. Exenatide and the treatment of patients with Parkinson’s disease. J Clin Invest 2013; 123 (06) 2730-6.
    CrossrefPubMedSearch in Google Scholar
  • 54 Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Kahan J, Ell P. et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson’s disease. J Park Dis 2014; 04 (03) 337-44.
    Search in Google Scholar
  • 55 Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K. et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet 2017; 390 (10103): 1664-75.
    CrossrefPubMedSearch in Google Scholar
  • 56 Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ. et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science 2017; 357 (6354): 891-8.
    CrossrefPubMedSearch in Google Scholar
  • 57 Salat D, Noyce AJ, Schrag A, Tolosa E. Challenges of modifying disease progression in prediagnostic Parkinson’s disease. Lancet Neurol 2016; 15 (06) 637-48.
    CrossrefPubMedSearch in Google Scholar
  • 58 Okun MS. Management of Parkinson Disease in 2017: Personalized Approaches for Patient-Specific Needs. JAMA 2017; 318 (09) 791-2.
    CrossrefPubMedSearch in Google Scholar