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psychoneuro 2003; 29(10): 462-468
DOI: 10.1055/s-2003-43531
Originalarbeit

© Georg Thieme Verlag Stuttgart · New York

Eine offene, beobachtende Studie - Therapie des Morbus Parkinson mit retardiertem Levodopa/Carbidopa

Thomas Müller1 , Martin Kungel2 , Petra Rink2
  • 1Neurologische Universitätsklinik im St. Josef-Hospital, Ruhr-Universität Bochum, Bochum
  • 2Bristol-Myers Squibb, München
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Publikationsverlauf

Publikationsdatum:
10. November 2003 (online)

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Zusammenfassung

Retardiertes Levodopa/Carbidopa wird meist zur Vermeidung von nächtlichen Akinesen bei Patienten mit idiopathischem Morbus Parkinson abends eingesetzt. Ziel dieser offenen beobachtenden Studie mit 338 Parkinson-Patienten war, die Sicherheit, Verträglichkeit und Wirksamkeit während eines zwölfwöchigen Untersuchungszeitraumes zu dokumentieren. Die tägliche Dosis von retardiertem Levodopa/Carbidopa (Nacom® retard) wurde bis zum Ende der Studie entsprechend der Fachinformation auf 372 mg gesteigert. Darunter besserten sich signifikant Akinese, Rigor, Tremor, sowie Ausprägung von Dyskinesien und motorischen Fluktuationen. Die Verträglichkeit war gut, Nebenwirkungen traten nur bei zwei Patienten auf. Diese offene Studie zeigt, dass durch Erhöhung bzw. Titrierung des retardierten Levodopa-Präparats eine verbesserte Einstellung der Symptome nahezu ohne ernsthafte, die Lebensqualität beeinträchtigende Nebenwirkungen erreicht werden kann. Auch kann eine Verbesserung von Fluktuationen und Dyskinesien kurzfristig erzielt werden.

Summary

Sustained release levodopa/carbidopa formulations are mostly administered for the treatment for nocturnal akinetic episodes in patients with idiopathic Parkinson's disease (PD) in the evening. Objectives of this 12 week open observational trial on controlled release levodopa/carbidopa preparations (Nacom® retard) were, to demonstrate their safety, tolerability and efficacy in 338 previously treated PD patients. Daily dosage of sustained release levodopa/carbidopa was elevated to 372mg during the study interval. Akinesia, rigidity, tremor, intensity of fluctuations and dyskinesias significantly improved. The tolerability was good, only two adverse events appeared. This open observational trial shows, that elevation and/or titration of sustained release levodopa/carbidopa preparation induces reduction of PD symptoms and motor complications without additional appearance essentially quality of life reducing, concomitant side effects in the short-term.

Keywords:

parkinson - dopa - nacom - sinemet

Literatur

  • 1 Cotzias GC, Duby S, Ginos JZ, Steck A, Papavasiliou PS. Dopamine analogues for studies of parkinsonism.  N Engl J Med. 1970;  283 1289
    PubMedGoogle Scholar
  • 2 Wajsbort J, Dorner A, Wajsbort E. A comparative clinical investigation of the therapeutic effect of levodopa alone and in combination with a decarboxylase inhibitor (carbidopa) in cases of Parkinson's disease.  Curr Med Res Opin. 1978;  5 695-708
    PubMedGoogle Scholar
  • 3 Müller T. Dopaminergic substitution in Parkinson's disease.  Expert Opin Pharmacother. 2002;  3 1393-403
    CrossrefPubMedGoogle Scholar
  • 4 Müller T, Benz S, Bornke C, Russ H, Przuntek H. Repeated rating improves value of diagnostic dopaminergic challenge tests in Parkinson's disease.  J Neural Transm. 2003;  110 603-9
    CrossrefPubMedGoogle Scholar
  • 5 Agid Y. Levodopa: is toxicity a myth?.  Neurology. 1998;  50 858-63
    PubMedGoogle Scholar
  • 6 Agid Y, Chase T, Marsden D. Adverse reactions to levodopa: drug toxicity or progression of disease?.  Lancet. 1998;  351 851-2
    CrossrefPubMedGoogle Scholar
  • 7 Fahn S. Controversies in the therapy of Parkinson's disease.  Adv Neurol. 1996;  69 477-86
    PubMedGoogle Scholar
  • 8 Fahn S. Is levodopa toxic?.  Neurology. 1996;  47 184-195
    PubMedGoogle Scholar
  • 9 Lees AJ. L-dopa treatment and Parkinson's disease.  Q J Med. 1986;  59 535-47
    PubMedGoogle Scholar
  • 10 Pfeiffer R. Optimization of levodopa therapy.  Neurology. 1992;  42 39-43
    PubMedGoogle Scholar
  • 11 Quinn N. Drug treatment of Parkinson's disease.  BMJ. 1995;  310 575-9
    PubMedGoogle Scholar
  • 12 Melamed E, Hefti F. Altered pharmacokinetics of L-dopa metabolism.  Neurology. 1985;  35 939-41
    PubMedGoogle Scholar
  • 13 Murata M, Kanazawa I. Effects of chronic levodopa therapy on dopa pharmacokinetics.  Eur Neurol. 1997;  38 50-5
    PubMedGoogle Scholar
  • 14 Robertson DR, Renwick AG, Wood ND, Cross N, Macklin BS, Fleming JS. et al. . The influence of levodopa on gastric emptying in man.  Br J Clin Pharmacol. 1990;  29 47-53
    PubMedGoogle Scholar
  • 15 Yeh KC, August TF, Bush DF, Lasseter KC, Musson DG, Schwartz S. et al. . Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies.  Neurology. 1989;  25-38
    PubMedGoogle Scholar
  • 16 Gerlach M, Kuhn W, Müller T, Klotz P, Przuntek H. Sustained-release of levodopa: single dose study of a new formulation.  J Neural Transm Gen Sect. 1996;  103 717-27
    CrossrefPubMedGoogle Scholar
  • 17 Hardie RJ, Malcolm SL, Lees AJ, Stern GM, Allen JG. The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on-off fluctuations.  Br J Clin Pharmacol. 1986;  22 429-36
    PubMedGoogle Scholar
  • 18 Kurlan R, Nutt JG, Woodward WR, Rothfield K, Lichter D, Miller C. et al. . Duodenal and gastric delivery of levodopa in parkinsonism.  Ann Neurol. 1988;  23 589-95
    CrossrefPubMedGoogle Scholar
  • 19 Kurth MC. Using liquid levodopa in the treatment of Parkinson's disease. A practical guide.  Drugs Aging. 1997;  10 332-40
    PubMedGoogle Scholar
  • 20 Pappert EJ, Goetz CG, Niederman F, Ling ZD, Stebbins GT, Carvey PM. Liquid levodopa/carbidopa produces significant improvement in motor function without dyskinesia exacerbation.  Neurology. 1996;  47 1493-5
    PubMedGoogle Scholar
  • 21 Przuntek H, Welzel D, Gerlach M, Blumner E, Danielczyk W, Kaiser HJ. et al. . Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study.  J Neural Transm Gen Sect. 1996;  103 699-715
    CrossrefPubMedGoogle Scholar
  • 22 Rascol O, Brooks DJ, Korczyn AD, De PP Deyn, Clarke CE, Lang AE. 056 Study Group . A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.  N Engl J Med. 2000;  342 1484-91
    CrossrefPubMedGoogle Scholar
  • 23 Poewe WH, Lees AJ, Stern GM. Clinical and pharmacokinetic observations with Madopar HBS in hospitalized patients with Parkinson's disease and motor fluctuations.  Eur Neurol. 1987;  27 93-7
    PubMedGoogle Scholar
  • 24 Rondot P, Ziegler M, Aymard N, Teinturier A. Effect of controlled-release carbidopa/levodopa on motor performance in advanced Parkinson's disease.  Neurology. 1989;  39 74-7
    PubMedGoogle Scholar
  • 25 Sage JI, Mark MH. Pharmacokinetics of continuous-release carbidopa/levodopa.  Clin Neuropharmacol. 1994;  17 1-6
    CrossrefPubMedGoogle Scholar
  • 26 Le Witt PA. Clinical studies with and pharmacokinetic considerations of sustained-release levodopa.  Neurology. 1992;  42 29-32
    PubMedGoogle Scholar
  • 27 MacMahon DG, Sachdev D, Boddie HG, Ellis CJ, Kendal BR, Blackburn NA. A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson's disease.  J Neurol Neurosurg Psychiatry. 1990;  53 220-3
    PubMedGoogle Scholar
  • 28 Malcolm SL, Allen JG, Bird H, Quinn NP, Marion MH, Marsden CD. et al. . Single-dose pharmacokinetics of Madopar HBS in patients and effect of food and antacid on the absorption of Madopar HBS in volunteers.  Eur Neurol. 1987;  27 28-35
    PubMedGoogle Scholar
  • 29 Stocchi F, Quinn NP, Barbato L, Patsalos PN, O'Connel MT, Ruggieri S. et al. . Comparison between a fast and a slow release preparation of levodopa and a combination of the two: a clinical and pharmacokinetic study.  Clin Neuropharmacol. 1994;  17 38-44
    PubMedGoogle Scholar
  • 30 Scheife RT, Schumock GT, Burstein A, Gottwald MD, Luer MS. Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes.  Am J Health Syst Pharm. 2000;  57 953-62
    PubMedGoogle Scholar
  • 31 Clarke CE. Medical management of Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2002;  72 22-27
    CrossrefPubMedGoogle Scholar
  • 32 Maurel F, Lilliu H, Le Pen C. [Social and economic cost of L-Dopa-induced dyskinesias in patients with Parkinson's disease].  Rev Neurol (Paris). 2001;  157 507-14
    PubMedGoogle Scholar
  • 33 Singer E. Social costs of Parkinson's disease.  J Chronic Dis. 1973;  26 243-54
    CrossrefPubMedGoogle Scholar
  • 34 Stamm T, Spycher S, Engfer A, Fahrenkrug E. Krankheitskosten des Morbus Parkinson in Deutschland.  Psycho. 1996;  22 212-28
    PubMedGoogle Scholar
  • 35 Cedarbaum JM, Kutt H, McDowell FH. A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100).  Neurology. 1989;  39 38-44
    PubMedGoogle Scholar
  • 36 Manyam BV, Hare TA, Robbs R, Cubberley VB. Evaluation of equivalent efficacy of sinemet and sinemet CR in patients with Parkinson's disease applying levodopa dosage conversion formula.  Clin Neuropharmacol. 1999;  22 33-9
    PubMedGoogle Scholar
  • 37 Block G, Liss C, Reines S, Irr J, Nibbelink D. Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson's disease. A multicenter 5-year study.  The CR First Study Group. Eur Neurol. 1997;  37 23-7
    PubMedGoogle Scholar
  • 38 Koller WC, Hutton JT, Tolosa E, Capilldeo R. Carbidopa/Levodopa Study Group. . Immediate-release and controlled-release carbidopa/levodopa in PD: a 5- year randomized multicenter study.  Neurology. 1999;  53 1012-9
    CrossrefPubMedGoogle Scholar
  • 39 Parkinson Study Group . Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group.  JAMA. 2000;  284 1931-8
    CrossrefPubMedGoogle Scholar
  • 40 Przuntek H, Welzel D, Gerlach M, Blumner E, Danielczyk W, Kaiser HJ. et al. . Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study.  J Neural Transm Gen Sect. 1996;  103 699-715
    CrossrefPubMedGoogle Scholar
  • 41 Rinne UK, Bracco F, Chouza C, Dupont E, Gershanik O, Marti JF Masso. et al. . Early treatment of Parkinson's disease with cabergoline delays the onset of motor complications. Results of a double-blind levodopa controlled trial.  The PKDS009 Study Group. Drugs. 1998;  55 23-30
    CrossrefPubMedGoogle Scholar
  • 42 Cedarbaum JM, Breck L, Kutt H, Mc Dowell FH. Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease.  Neurology. 1987;  37 233-41
    PubMedGoogle Scholar
  • 43 Chouza C, Aljanati R, Caamano JL, De Medina O, Scaramelli A, Buzo R. et al. . Long-term treatment with Madopar HBS in parkinsonians with fluctuations.  Adv Neurol. 1990;  53 519-26
    PubMedGoogle Scholar
  • 44 Deleu D, Jacques M, Michotte Y, Ebinger G. Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations.  Neurology. 1989;  39 88-92
    PubMedGoogle Scholar
  • 45 Jankovic J, Schwartz K, Vander LC. Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations.  Mov Disord. 1989;  4 303-9
    CrossrefPubMedGoogle Scholar
  • 46 Pezzoli G, Tesei S, Ferrante C, Cossutta E, Zecchinelli A, Scarlato G. Madopar HBS in fluctuating parkinsonian patients: two-year treatment.  Mov Disord. 1988;  3 37-45
    CrossrefPubMedGoogle Scholar

Korrespondenzadresse:

Prof. Dr. Thomas Müller

Neurologische Universitätsklinik im St. Josef-Hospital, Ruhr-Universität Bochum

Gudrunstr. 56

44791 Bochum

Germany

eMail: thomas.mueller@ruhr-uni-bochum.de