Nervenheilkunde 2004; 23(03): 174-180
DOI: 10.1055/s-0038-1626290
Forum Psychopharmacologicum
Schattauer GmbH

Die fixe Kombination von Levodopa/Carbidopa mit Entacapon in der Parkinson-Therapie

Fix combination of levodopa/carbidopa with entacapone in the treatment of Parkinson’s disease
T. Müller
1   Neurologische Universitätsklinik im St. Josef-Hospital, Ruhr-Universität Bochum
,
J. P. Sieb
2   Neurologie am Max-Planck-Institut für Psychiatrie, München
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
19. Januar 2018 (online)

Zusammenfassung

Der Catechol-O-Methyltransferase-Hemmer Entacapon ist eine in der medikamentösen Parkinsontherapie etablierte Substanz. Sie erweitert das therapeutische Spektrum durch Hemmung des Abbaus von Levodopa (LD) in der Peripherie, womit die Wirkung von LD verstärkt wird. Entacapon ist nur in Kombination mit LD und besonders bei Patienten mit vorhersagbaren Fluktuationen der Beweglichkeit wirksam. Nebenwirkungen können eine Verstärkung von Dyskinesien, Diarrhoe, Blutdruckabfall und Urinverfärbung sein. Da Entacapon meist gleichzeitig mit jeder LD/Decarboxylasehemmer (DCH)-Dosis verabreicht wird, erhöht dies deutlich die Anzahl der einzunehmenden Tabletten, was klinisch oft die Medikamentencompliance beeinträchtigt. Die Zulassung von Stalevo®, der fixen Kombination von LD/Carbidopa (CD) in drei verschiedenen Dosierungen (50 LD/12,5 CD, 100 LD/25 CD, 150 LD/37.5 CD [mg]) und Enta-capon (200 mg) in einer Tablette, umgeht dieses Problem. Wir schildern zusammenfassend das optimierte therapeutische Vorgehen der LD/DCI-Gabe mit Entacapon in der Behandlung des Morbus Parkinson und versuchen erste praktische, therapeutische Richtlinien für den Einsatz dieses neuen Kombinationspräparates zu geben. Basierend auf den positiven Ergebnissen der Multizenterstudien mit Entacapon schlagen wir den Einsatz dieser fixen Kombination von LD/CD/Entacapon insbesondere bei Parkinsonpatienten mit End-off-doseFluktuationen vor.

Summary

The catechol-O-methyltransferase inhibitor entacapone is an established drug, which expands the therapeutic options for the treatment of Parkinson’s disease (PD) by extending the action of levodopa (LD) due to inhibition of its peripheral metabolism. Entacapone is solely used in conjunction with LD and particularly provides symptomatic benefit to PD patients who suffer from predictable motor fluctuations. Possible side effects may include worsening of dyskinesias, hypotension, constipation and urine discoloration. The postulated therapeutic concept of simultaneous administration of entacapone with each levodopa/decarboxylase inhibitor (DCI) dose often markedly increased intake of tablets, which may cause compliance problems. The launch of Stalevo®, the fix combination of LD/carbidopa (CD) in the three different dosages (50 LD/12.5 CD, 100 LD/25 CD, 150 LD/ 37.5 CD [mg]) and entacapone (200 mg) in one tablet, may circumvent this issue. We review this optimized therapeutic approach of LD/DCI administration with entacapone in the drug therapy of idiopathic PD and try to provide initial therapeutic guidelines for the use of this novel LD/CD/entacapone formulation. We suggest the preponderant application of this LD/CD/entacapone preparation in PD patients with end-off dose fluctuations according to the positive outcomes of previous multicenter trials with entacapone.

 
  • Literatur

  • 1 Müller T, Benz S, Börnke 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.
  • 2 Müller T. Dopaminergic substitution in Parkinson’s disease. Expert Opin Pharmacother 2002; 03: 1393-403.
  • 3 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.
  • 4 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.
  • 5 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.
  • 6 Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa 056 Study Group. N Engl J Med 2000; 342: 1484-91.
  • 7 Cedarbaum JM, Breck L, Kutt H, McDowell FH. Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson’s disease. Neurology 1987; 233-41.
  • 8 Dupont E, Andersen A, Boas J, Boisen E, Borgmann R, Helgetveit AC. et al. Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients. Acta Neurol Scand 1996; 93: 14-20.
  • 9 Jansen EN, Meerwaldt JD. Madopar HBS in Parkinson patients with nocturnal akinesia. Clin Neurol Neurosurg 1988; 90: 35-9.
  • 10 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.
  • 11 Koller WC, Hutton JT, Tolosa E, Capilldeo R. Immediate-release and controlled-release carbidopa/levodopa in PD: a 5year randomized multicenter study. Carbidopa/Levodopa Study Group. Neurology 1999; 53: 1012-9.
  • 12 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.
  • 13 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.
  • 14 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; 04: 303-9.
  • 15 Pezzoli G, Tesei S, Ferrante C, Cossutta E, Zecchinelli A, Scarlato G. Madopar HBS in fluctuating parkinsonian patients: two-year treatment. Mov Disord 1988; 03: 37-45.
  • 16 Clarke CE. Medical management of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2002; 72 (Suppl. 01) I22-7.
  • 17 Ahlskog JE. Slowing Parkinson’s disease progression. Recent dopamine agonist trials. Neurology 2003; 60: 381-9.
  • 18 Rascol O, Brooks DJ, Korczyn AD, DeDeyn PP, Clarke CE, Lang AE. 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.
  • 19 Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. JAMA 2000; 284: 1931-8.
  • 20 Pearce RK, Heikkilä M, Linden IB, Jenner P. L-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations. Psychopharmacology (Berl) 2001; 156: 402-9.
  • 21 Jenner P. The contribution of the MPTP-treated primate model to the development of new treatment strategies for Parkinson’s disease. Parkinsonism Relat Disord 2003; 09: 131-7.
  • 22 Smith LA, Jackson MJ, Hansard MJ, Maratos E, Jenner P. Effect of pulsatile administration of levodopa on dyskinesia induction in drug-naive MPTP-treated common marmosets: Effect of dose, frequency of administration, and brain exposure. Mov Disord 2003; 18: 487-95.
  • 23 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.
  • 24 Cedarbaum JM. Clinical pharmcokinetics of anti-parkinsonian drugs. Clin Pharmacokinet 1987; 13: 141-78.
  • 25 Benetello P, Furlanut M, Fortunato M, Pea F, Baraldo M. Levodopa and 3-O-methyldopa in cerebrospinal fluid after levodopa-carbidopa association. Pharmacol Res 1997; 35: 313-5.
  • 26 Ahtila S, Kaakkola S, Gordin A, Korpela K, Heinavaara S, Karlsson M. et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers. Clin Neuropharmacol 1995; 18: 46-57.
  • 27 Keränen T, Gordin A, Harjola VP, Karlsson M, Korpela K, Pentikainen PJ. et al. The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Clin Neuropharmacol 1993; 16: 145-56.
  • 28 Ruottinen HM, Rinne UK. Effect of one month’s treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Clin Neuropharmacol 1996; 19: 222-33.
  • 29 Ruottinen HM, Rinne UK. A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjuvant to levodopa therapy in advanced Parkinson’s disease. Clin Neuropharmacol 1996; 19: 283-96.
  • 30 Kaakkola S, Teräväinen H, Ahtila S, Rita H, Gordin A. Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients. Neurology 1994; 44: 77-80.
  • 31 Myllylä VV, Sotaniemi KA, Illi A, Suominen K, Keränen T. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics of levodopa and on cardiovascular responses in patients with Parkinson’s disease. Eur J Clin Pharmacol 1993; 45: 419-23.
  • 32 Nutt JG, Woodward WR, Beckner RM, Stone CK, Berggren K, Carter JH. et al. Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 1994; 44: 913-9.
  • 33 Keränen T, Gordin A, Karlsson M, Korpela K, Pentikainen PJ, Rita H. et al. Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone. Eur J Clin Pharmacol 1994; 46: 151-7.
  • 34 Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Järvinen T, Männistö PT. Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther 2003; 304: 498-506.
  • 35 Heikkinen H, Saraheimo M, Antila S, Ottoila P, Pentikainen PJ. Pharmacokinetics of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, in man. A study using a stable isotope techique. Eur J Clin Pharmacol 2001; 56: 821-6.
  • 36 Lyytinen J, Sovijarvi A, Kaakkola S, Gordin A, Teravainen H. The effect of catechol-O-methyltransferase inhibition with entacapone on cardiovascular autonomic responses in L-Dopatreated patients with Parkinson’s disease. Clin Neuropharmacol 2001; 24: 50-7.
  • 37 Müller T, Kuhn W, Przuntek H. Therapy with central active catechol-O-methyltransferase (COMT)inhibitors: is addition of monoamine oxidase (MAO)-inhibitors necessary to slow progress of neurodegenerative disorders?. J Neural Transm Gen Sect 1993; 92: 187-95.
  • 38 Müller T, Woitalla D, Schulz D, Peters S, Kuhn W, Przuntek H. Tolcapone increases maximum concentration of levodopa. J Neural Transm 2000; 107: 113-9.
  • 39 Parkinson Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 1997; 42: 747-55.
  • 40 Rinne UK, Larsen JP, Siden Å, Worm-Petersen J. Nomecomt Study Group. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998; 51: 1309-14.
  • 41 Larsen JP, Worm-Petersen J, Sidén Å, Gordin A, Reinikainen K, Leinonen M. et al. The tolerability and efficacy of entacapone over 3 years in patients with Parkinson’s disease. Eur J Neurol 2003; 10: 137-46.
  • 42 Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand 2002; 105: 245-55.
  • 43 Myllyla VV, Kultalahti ER, Haapaniemi H, Leinonen M. Twelve-month safety of entacapone in patients with Parkinson’s disease. Eur J Neurol 2001; 08: 53-60.
  • 44 Brooks DJ, Sagar H. UK-Irish Entacapone Study Group. Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry 2003; 74: 1071-9.
  • 45 Nuijten MJ, VanIperen P, Palmer C, VanHilten BJ, Snyder E. Cost-effectiveness analysis of entacapone in Parkinson’s disease: A Markov process analysis. Value in Health 2001; 04: 316-28.
  • 46 Piccini P, Brooks DJ, Korpela K, Pavese N, Karlsson M, Gordin A. The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson’s disease. 2000
  • 47 Müller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parkinson’s disease [letter]. Lancet 1999; 354: 126-7.
  • 48 Miller JW, Shukitt-Hale B, Villalobos-Molina R, Nadeau MR, Selhub J, Joseph JA. Effect of L-Dopa and the catechol-O-methyltransferase inhibitor Ro 410960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 1997; 20: 55-66.
  • 49 Ben Shlomo Y, Marmot MG. Survival and cause of death in a cohort of patients with parkinsonism: possible clues to aetiology?. J Neurol Neurosurg Psychiatry 1995; 58: 293-9.
  • 50 Gorell JM, Johnson CC, Rybicki BA. Parkinson’s disease and its comorbid disorders: an analysis of Michigan mortality data, 1970 to 1990. Neurology 1994; 44: 1865-8.