Principles of personalized medicine and modern pharmaceutical technologies to optimize levodopa therapy of Parkinson's disease
- Authors: Abaimov D.А.1, Fedotova E.Y.1, Poleshchuk V.V.2, Andreev M.N.1, Trifonova O.P.3, Lokhov P.G.3, Illarioshkin S.N.1
-
Affiliations:
- Research Center of Neurology
- Research Center of Neurology,
- Institute of Biomedical Chemistry
- Issue: Vol 15, No 2 (2021)
- Pages: 73-82
- Section: Technologies
- Submitted: 16.06.2021
- Published: 17.06.2021
- URL: https://annaly-nevrologii.com/journal/pathID/article/view/749
- DOI: https://doi.org/10.25692/ACEN.2021.2.9
- ID: 749
Cite item
Full Text
Abstract
Levodopa (3-hydroxy-L-tyrosine, the levorotatory isomer of 3,4-dihydroxyphenylalanine) is a biological precursor of the neurotransmitter dopamine and has been the "gold standard" in the treatment of Parkinson’s disease for over 50 years. The widespread use of levodopa in clinical practice has not only provided neurologists with unique data from many years of symptomatic replacement therapy for a severe neurodegenerative disease but has also clearly identified several serious problems associated with levodopa absorption and metabolism. This article discusses the modern approaches to personalized medicine, which aim to overcome the numerous difficulties in managing patients with Parkinson’s disease and long-term levodopa use. A major focus is the review of strategies for selecting the optimal levodopa dosage regimen in specific patients and the main innovative dosage forms of this drug that improve its pharmacokinetics.
About the authors
Denis А. Abaimov
Research Center of Neurology
Author for correspondence.
Email: abaimov@neurology.ru
Россия, Moscow
Ekaterina Yu. Fedotova
Research Center of Neurology
Email: abaimov@neurology.ru
Россия, Moscow
Vsevolod V. Poleshchuk
Research Center of Neurology,
Email: abaimov@neurology.ru
Россия, Moscow
Maksim N. Andreev
Research Center of Neurology
Email: abaimov@neurology.ru
Россия, Moscow
Oxana P. Trifonova
Institute of Biomedical Chemistry
Email: abaimov@neurology.ru
Россия, Moscow
Petr G. Lokhov
Institute of Biomedical Chemistry
Email: abaimov@neurology.ru
Россия, Moscow
Sergey N. Illarioshkin
Research Center of Neurology
Email: abaimov@neurology.ru
Россия, Moscow
References
- Tysnes O.B., Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm. 2017; 124(8): 901–905. doi: 10.1007/s00702-017-1686-y. PMID: 28150045.
- Deleu D., Northway M.G., Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinetics. 2002; 41(4): 261–309. doi: 10.2165/00003088-200241040-00003. PMID: 11978145.
- Hornykiewicz O. A brief history of levodopa. J Neurol. 2010; 257(2): 249–252. doi: 10.1007/s00415-010-5741-y. PMID: 21080185.
- Kaakkola S., Männistö P., Nissinen E. et al. The effect of an increased ratio of carbidopa to levodopa on the pharmacokinetics of levodopa. Acta Neurol Scand. 1985; 72(4): 385–391. doi: 10.1111/j.1600-0404.1985.tb00888.x. PMID: 4082903.
- Nutt J.G., Woodward W.R., Anderson J.L. The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism. Ann Neurol. 1985; 18(5): 537–543. doi: 10.1002/ana.410180505. PMID: 4073849.
- Durso R., Evans J.E., Josephs E. et al. Variable absorption of carbidopa affects both peripheral and central levodopa metabolism. J Clin Pharmacol. 2000; 40(8): 854–860. doi: 10.1177/00912700022009585. PMID: 10934669.
- Pincus J.H., Barry K.M. Plasma levels of amino acids correlate with motor fluctuations in parkinsonism. Arch Neurol. 1987; 44(10): 1006–1009. doi: 10.1001/archneur.1987.00520220012007. PMID: 3632370.
- Frankel J., Kempster P., Bovingdon M. et al. The effects of oral protein on the absorption of intraduodenal levodopa and motor performance. J Neurol Neurosurg Psychiatry. 1989; 52(9): 1063–1067. doi: 10.1136/jnnp.52.9.1063. PMID: 2795076.
- Alexander G.M., Schwartzman R.J., Grothusen J.R., Gordon S.W. Effect of plasma levels of large neutral amino acids and degree of parkinsonism on the blood‐to‐brain transport of levodopa in naive and MPTP parkinsonian monkeys. Neurology. 1994; 44(8): 1491–1499. doi: 10.1212/wnl.44.8.1491. PMID: 8058155.
- Sheard J.M., Ash S., Silburn P.A., Kerr G.K. Nutritional status in Parkinson's disease patients undergoing deep brain stimulation surgery: a pilot study. J Nutrition Health & Aging. 2013; 17(2): 148–151. doi: 10.1007/s12603-012-0386-4. PMID: 23364493.
- Lee E.S., Chen H., King J., Charlton C. The role of 3-O-methyldopa in the side effects of L-dopa. Neurochem Res. 2008; 33(3): 401–411. doi: 10.1007/s11064-007-9442-6. PMID: 17713853.
- Müller T., Möhr J.D. Long-term management of Parkinson's disease using levodopa combinations. Exp Opin Pharmacother. 2018; 19(9): 1003–1011. doi: 10.1080/14656566.2018.1484108. PMID: 29913079.
- Gancher S.T., Nutt J.G., Woodward W.R. Peripheral pharmacokinetics of levodopa in untreated, stable, and fluctuating parkinsonian patients. Neurology. 1987; 37(6): 940–950. doi: 10.1212/wnl.37.6.940. PMID: 3587644.
- Chase T., Mouradian M., Fabbrini G., Juncos J. Pathogenetic studies of motor fluctuations in Parkinson’s disease. J Neural Transm Suppl. 1988; 27: 3–10. doi: 10.1007/978-3-7091-8954-2_1. PMID: 3042912.
- Olanow C.W., Gauger L.L., Cedarbaum J.M. Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. Ann Neurol. 1991; 29(5): 556–559. doi: 10.1002/ana.410290516. PMID: 1859185.
- Andersen A.D., Blaabjerg M., Binzer M. et al. Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia. J Neurochem. 2017; 141(4): 614–625. doi: 10.1111/jnc.13997. PMID: 28244186.
- Nutt J.G., Woodward W.R., Gancher S.T., Merrick D. 3‐O‐Methyldopa and the response to levodopa in Parkinson's disease. Ann Neurol. 1987; 21(6): 584–588. doi: 10.1002/ana.410210610. PMID: 3606046.
- Tohgi H., Abe T., Takahashi S. et al. Alterations in the concentration of serotonergic and dopaminergic substances in the cerebrospinal fluid of patients with Parkinson's disease, and their changes after l-dopa administration. Neurosci Lett. 1993; 159(1): 135–138. doi: 10.1016/0304-3940(93)90817-5. PMID: 7505410.
- Koller W.C., Pahwa R. Treating motor fluctuations with controlled-release levodopa preparations. Neurology. 1994; 44 (7 Suppl. 6): S23–S28. PMID: 8047257.
- Contin M., Riva R., Martinelli P. et al. Levodopa therapy monitoring in patients with Parkinson disease: a kinetic–dynamic approach. Ther Drug Monitor. 2001; 23(6): 621–629. doi: 10.1097/00007691-200112000-00005. PMID: 11802094.
- Sage J.I., Mark M.H., McHale D.M. et al. Benefits of monitoring plasma levodopa in Parkinson's disease patients with drug‐induced chorea. Ann Neurol. 1991; 29(6): 623–628. doi: 10.1002/ana.410290609. PMID: 1892365.
- Benetello P., Furlanut M., Zara G. et al. Plasma levels of levodopa and its main metabolites in parkinsonian patients after conventional and controlled-release levodopa-carbidopa associations. Eur Neurol. 1993; 33(1): 69–73. doi: 10.1159/000116905. PMID: 8440292.
- Muenter M., Tyce G. L-dopa therapy of Parkinson's disease: plasma L-dopa concentration, therapeutic response, and side effects. Mayo Clinic Proc. 1971; 46(4): 231–239. PMID: 5573818.
- Pilling J., Baker J., Iversen L. et al. Plasma concentrations of L-dopa and 3-methoxydopa and improvement in clinical ratings and motor performance in patients with Parkinsonism treated with L-dopa alone or in combination with amantadine. J Neurol Neurosurg Psychiatry. 1975; 38(2): 129–135. doi: 10.1136/jnnp.38.2.129. PMID: 1097598.
- Rinne U., Sonninen V., Siirtola T. Plasma concentration of levodopa in patients with Parkinson’s disease. Eur Neurol. 1973; 10(5): 301–310. doi: 10.1159/000114285. PMID: 4789106.
- Furlanut M., Furlanut Jr.M., Benetello P. Monitoring of L-dopa concentrations in Parkinson’s disease. Pharmacol Res. 2001; 43(5):423-427. doi: 10.1006/phrs.2001.0819. PMID: 11394933.
- Jimenez-Shahed J. A review of current and novel levodopa formulations for the treatment of Parkinson's disease. Ther Deliv. 2016; 7(3): 179–191. doi: 10.4155/tde.15.96. PMID: 26893250.
- Yeh K., August T., Bush D. et al. Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. Neurology. 1989; 39 (11 Suppl. 2): 25-38. PMID: 2685649.
- Gauthier S., Amyot D. Sustained release antiparkinson agents: controlled release levodopa. Can J Neurol Sci. 1992; 19(S1): 153–155. PMID: 1571861.
- Nausieda P.A., Pfeiffer R.F., Tagliati M. et al. A multicenter, open-label, sequential study comparingpreferences for carbidopa-levodopa orally disintegrating tablets and conventional tablets in subjects with Parkinson's disease. Clin Ther. 2005; 27(1): 58–63. doi: 10.1016/j.clinthera.2005.01.004. PMID: 15763606.
- Brooks D.J., Sagar H., Group U-IES. 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(8): 1071–1079. doi: 10.1136/jnnp.74.8.1071. PMID: 12876237.
- Poewe W., Deuschl G., Gordin A. et al. 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(4): 245–255. doi: 10.1034/j.1600-0404.2002.1o174.x. PMID: 11939936.
- Kuoppamäki M., Vahteristo M., Ellmén J., Kieburtz K. Pooled analysis of phase III with entacapone in Parkinson's disease. Acta Neurol Scand. 2014; 130(4): 239–247. doi: 10.1111/ane.12278. PMID: 25186800.
- Stocchi F., Rascol O., Kieburtz K. et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE‐PD study. Ann Neurol. 2010; 68(1): 18–27. doi: 10.1002/ana.22060. PMID: 20582993.
- Muhlack S., Herrmann L., Salmen S., Müller T. Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition. J Neural Transm. 2014; 121(11): 1357–1366. doi: 10.1007/s00702-014-1213-3. PMID: 24770794.
- Hauser R.A., Hsu A., Kell S. 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(4): 346–356. doi: 10.1016/S1474-4422(13)70025-5. PMID: 23485610.
- Pahwa R., Lyons K.E., Hauser R.A. et al. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord. 2014; 20(2): 142–148. doi: 10.1016/j.parkreldis.2013.08.017. PMID: 24055014.
- Hauser R.A., Ellenbogen A.L., Metman L.V. et al. Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease. Mov Disord. 2011; 26(12): 2246–2252. doi: 10.1002/mds.23861. PMID: 21755537.
- Fernandez H., Odin P. Levodopa-carbidopa intestinal gel for treatment of advanced Parkinson’s disease. Curr Med Res Opin. 2011; 27(5): 907–919. doi: 10.1185/03007995.2011.560146. PMID: 21351823.
- Nyholm D., Remahl A.N., Dizdar N. et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology. 2005; 64(2): 216–223. doi: 10.1212/01.WNL.0000149637.70961.4C. PMID: 15668416.
- Senek M., Nielsen E.I., Nyholm D. Levodopa‐entacapone‐carbidopa intestinal gel in Parkinson's disease: A randomized crossover study. Mov. Disord. 2017; 32(2): 283–286. doi: 10.1002/mds.26855. PMID: 27987231.
- Poewe W., Antonini A. Novel formulations and modes of delivery of levodopa. Mov Disord. 2015; 30(1): 114–120. doi: 10.1002/mds.26078. PMID: 25476691.
- LeWitt P.A., Friedman H., Giladi N. et al. Accordion pill carbidopa/levodopa for improved treatment of advanced Parkinson’s disease symptoms. Mov Disord. 2012; 27 (Suppl. 1): S408.
- Verhagen M.L., Stover N., Chen C. et al. Gastroretentive carbidopa/levodopa, DM‐1992, for the treatment of advanced Parkinson's disease. Mov Disord. 2015; 30(9): 1222–1228. doi: 10.1002/mds.26219. PMID: 25847690.
- LeWitt P.A., Ellenbogen A., Chen D. et al. Actively transported levodopa prodrug XP21279: a study in patients with Parkinson disease who experience motor fluctuations. Clin Neuropharmacol. 2012; 35(3): 103–110. doi: 10.1097/WNF.0b013e31824e4d7d. PMID: 22406623.
- Stocchi F., Zappia M., Dall'Armi V. et al. Melevodopa/carbidopa effervescent formulation in the treatment of motor fluctuations in advanced Parkinson's disease. Mov Disord. 2010; 25(12): 1881–1887. doi: 10.1002/mds.23206. PMID: 20669296.
- Stocchi F., Vacca L., Grassini P. et al. L-dopa pharmacokinetic profile with effervescent melevodopa/carbidopa versus standard-release levodopa/carbidopa tablets in Parkinson’s disease: a randomised study. Parkinson’s Dis. 2015; 2015: 369465. doi: 10.1155/2015/369465. PMID: 26171276.
- Stocchi F., Barbato L., Bramante L. et al. The clinical efficacy of a single afternoon dose of levodopa methyl ester: a double-blind cross-over study versus placebo. Funct Neurol. 1994; 9(5): 259–264. PMID: 7750809.
- Bosco D., Plastino M., Bosco F. et al. Daily motor performance after switching levodopa to melevodopa: an open-label on advanced Parkinson's disease with «delayed-on» and/or «wearing-off». Minerva Med. 2011; 102(2): 125–132. PMID: 21483399.
- LeWitt P.A., Hauser R.A., Pahwa R. et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019; 18(2): 145–154. doi: 10.1016/s1474-4422(18)30405-8. PMID: 30663606.
- Freed M., Grosset D., Worth P. et al. Rapid levodopa augmentation following inhaled CVT-301 results in rapid improvement in motor response when administered to PD patients in the off state (S7. 007). AAN Enterprises. 2014.