Current Status and Challenges in Rotigotine Delivery

Author(s): Shadab Md*, Shahid Karim, Sanggetha R. Saker, Ooi A. Gie, Lim C. Hooi, Phua H. Yee, Alvin W.C. Kang, Chen K. Zhe, Ng Ian, Hibah M. Aldawsari, Khaled M. Hosny, Nabil A. Alhakamy*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 19 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Rotigotine is a non-ergoline, high lipophilic dopamine agonist. It is indicated as the first-line therapy for Parkinson's disease (PD) and Restless Leg Syndrome (RLS). However, the precise mechanism of rotigotine is yet to be known. Rotigotine has similar safety and tolerability to the other oral non-ergolinic dopamine antagonists in clinical trials, which include nausea, dizziness and somnolence. Neupro® was the first marketed transdermal patch formulation having rotigotine. The transdermal delivery system is advantageous as it enables continuous administration of the drug, thus providing steady-state plasma drug concentration for 24-hours. Intranasal administration of rotigotine allows the drug to bypass the blood-brain barrier enabling it to reach the central nervous system within minutes. Rotigotine can also be formulated as an extended-release microsphere for injection. Some challenges remain in other routes of rotigotine administration such as oral, parenteral and pulmonary, whereby resolving these challenges will be beneficial to patients as they are less invasive and comfortable in terms of administration. This review compiles recent work on rotigotine delivery, challenges and its future perspective.

Keywords: Rotigotine, microemulsion, microspheres, nanoparticles, transdermal delivery, Parkinson's Disease (PD).

[1]
Jenner P. A novel dopamine agonist for the transdermal treatment of Parkinson’s disease. Neurology 2005; 65(2)(Suppl. 1): S3-5.
[http://dx.doi.org/10.1212/WNL.65.2_suppl_1.S3] [PMID: 16030291]
[2]
Chen JJ, Swope DM, Dashtipour K, Lyons KE. Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson’s disease. Pharmacotherapy 2009; 29(12): 1452-67.
[http://dx.doi.org/10.1592/phco.29.12.1452] [PMID: 19947805]
[3]
Trenkwalder C, Winkelmann J, Inoue Y, Paulus W. Restless legs syndrome-current therapies and management of augmentation. Nat Rev Neurol 2015; 11(8): 434-45.
[http://dx.doi.org/10.1038/nrneurol.2015.122] [PMID: 26215616]
[4]
Benitez A, Edens H, Fishman J, Moran K, Asgharnejad M. Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson’s disease and restless legs syndrome. Ann N Y Acad Sci 2014; 1329(1): 45-66.
[http://dx.doi.org/10.1111/nyas.12508] [PMID: 25145951]
[5]
Baldwin CM, Keating GM. Rotigotine transdermal patch: in restless legs syndrome. CNS Drugs 2008; 22(10): 797-806.
[http://dx.doi.org/10.2165/00023210-200822100-00001] [PMID: 18788832]
[6]
Carranza M, Snyder MR. J Davenport Shaw TAZ Parkinson’s Disease: A Guide to Medical Treatment - Michael Carranza, Madeline R Snyder, Jessica Davenport Shaw, Theresa A Zesiewicz - Google Books. 1st ed. Torino, Italy: S EED 2013.
[7]
Elshoff JP, Braun M, Andreas JO, Middle M, Cawello W. Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies. Clin Ther 2012; 34(4): 966-78.
[http://dx.doi.org/10.1016/j.clinthera.2012.02.008] [PMID: 22401642]
[8]
Cawello W, Braun M, Boekens H. Absorption, disposition, metabolic fate, and elimination of the dopamine agonist rotigotine in man: administration by intravenous infusion or transdermal delivery. Drug Metab Dispos 2009; 37(10): 2055-60.
[http://dx.doi.org/10.1124/dmd.109.027383] [PMID: 19608695]
[9]
Cawello W, Ahrweiler S, Sulowicz W, Szymczakiewicz-Multanowska A, Braun M. Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function. Br J Clin Pharmacol 2012; 73(1): 46-54.
[http://dx.doi.org/10.1111/j.1365-2125.2011.04053.x] [PMID: 21707699]
[10]
Sprenger FS, Seppi K, Poewe W. Drug safety evaluation of rotigotine. Expert Opin Drug Saf 2012; 11(3): 503-12.
[http://dx.doi.org/10.1517/14740338.2012.678830] [PMID: 22468676]
[11]
Schnitzler A, Leffers KW, Häck HJ. High compliance with rotigotine transdermal patch in the treatment of idiopathic Parkinson’s disease. Parkinsonism Relat Disord 2010; 16(8): 513-6.
[http://dx.doi.org/10.1016/j.parkreldis.2010.06.009] [PMID: 20605106]
[12]
Frampton JE. Rotigotine transdermal patch: A review in Parkinson Disease. CNS Drugs 2019; 33(7): 707-18.
[http://dx.doi.org/10.1007/s40263-019-00646-y] [PMID: 31243728]
[13]
Trenkwalder C, Kies B, Rudzinska M, et al. Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 2011; 26(1): 90-9.
[http://dx.doi.org/10.1002/mds.23441] [PMID: 21322021]
[14]
Valldeoriola F, Salvador A, Gómez-Arguelles JM, et al. The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre, observational, retrospective, post-marketing study. Int J Neurosci 2018; 3(128(4)): 369-75.
[http://dx.doi.org/10.1080/00207454.2017.1387111]
[15]
Golfrè Andreasi N, Rispoli V, Contaldi E, et al. Deep brain stimulation and refractory freezing of gait in Parkinson’s disease: Improvement with high-frequency current steering co-stimulation of subthalamic nucleus and substantia Nigra. Brain Stimul 2020; 13(2): 280-3.
[http://dx.doi.org/10.1016/j.brs.2019.10.010] [PMID: 31836466]
[16]
Hauser RA, Slawek J, Barone P, et al. Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson’s disease. BMC Neurol 2016; 16(1): 90.
[http://dx.doi.org/10.1186/s12883-016-0610-7] [PMID: 27267880]
[17]
Calandra-Buonaura G, Guaraldi P, Doria A, et al. Rotigotine objectively improves sleep in Parkinson’s disease: an open-label pilot study with actigraphic recording. Parkinsons Dis 2016; 20163724148
[http://dx.doi.org/10.1155/2016/3724148] [PMID: 26981312]
[18]
Wang Y, Yang YC, Lan DM, Wu HJ, Zhao ZX. An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson’s disease. Sleep Breath 2017; 21(2): 319-25.
[http://dx.doi.org/10.1007/s11325-016-1414-0] [PMID: 27726069]
[19]
Chaudhuri KR, Martinez-Martin P, Antonini A, et al. Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER. Parkinsonism & related disorders 2013; 1;(19(7)): 660-5.
[http://dx.doi.org/10.1016/j.parkreldis.2013.02.018]
[20]
Cetin M, Gumru S, Aricioglu F. Nanotechnology Applications in Neuroscience: Advances, Opportunities and Challenges. Klin Psikofarmakol Bülteni-Bulletin Clin Psychopharmacol [Internet] 2012; 22(2): 115-20.
[http://dx.doi.org/10.5455/bcp.20120621044747]
[21]
Bi C, Wang A, Chu Y, et al. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment. Int J Nanomedicine 2016; 11: 6547-59.
[http://dx.doi.org/10.2147/IJN.S120939] [PMID: 27994458]
[22]
Gunay MS, Ozer AY, Chalon S. Drug Delivery Systems for Imaging and Therapy of Parkinson’s Disease. Curr Neuropharmacol 2016; 14(4): 376--19.15.
[23]
Adhikary RR, Sandbhor P, Banerjee R. Nanotechnology platforms in Parkinson’s Disease. ADMET DMPK 2015; 3(3): 155-81.
[http://dx.doi.org/10.5599/admet.3.3.189]
[24]
Alhakamy NA, Md S. Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers. Pharmaceutics 2019; 11(12): 685.
[http://dx.doi.org/10.3390/pharmaceutics11120685] [PMID: 31888155]
[25]
Md S, Kumar M, Baboota S, Sahni JK, Ali J. Preparation, Characterization and Evaluation of Bromocriptine Loaded Chitosan Nanoparticles for Intranasal Delivery. Sci Adv Mater 2012; 4(10): 1-12.
[26]
Han T, Das DB. Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. Eur J Pharm Biopharm 2015; 89: 312-28.
[http://dx.doi.org/10.1016/j.ejpb.2014.12.020] [PMID: 25541440]
[27]
Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv 2014; 11(3): 393-407.
[http://dx.doi.org/10.1517/17425247.2014.875528] [PMID: 24392787]
[28]
Kretsos K, Kasting GB. A geometrical model of dermal capillary clearance. Math Biosci 2007; 208(2): 430-53.
[http://dx.doi.org/10.1016/j.mbs.2006.10.012] [PMID: 17303187]
[29]
Donnelly RF, Singh TRR, Garland MJ, et al. Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater 2012; 22(23): 4879-90.
[http://dx.doi.org/10.1002/adfm.201200864] [PMID: 23606824]
[30]
Donnelly RF, Singh TRR, Morrow DIJ, Woolfson AD. Microneedle-Mediated Transdermal and Intradermal Drug Delivery Microneedle-Mediated Transdermal and Intradermal Drug Delivery. John Wiley & Sons, Ltd. 2012.
[http://dx.doi.org//10.1002/9781119959687]
[31]
Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 2015; 7(4): 438-70.
[http://dx.doi.org/10.3390/pharmaceutics7040438] [PMID: 26506371]
[32]
Singh P, Carrier A, Chen Y, et al. Polymeric microneedles for controlled transdermal drug delivery. J Control Release 2019; 315: 97-113.
[http://dx.doi.org/10.1016/j.jconrel.2019.10.022] [PMID: 31644938]
[33]
Ball AM, Smith KM. Optimizing transdermal drug therapy. Am J Health Syst Pharm 2008; 65(14): 1337-46.
[http://dx.doi.org/10.2146/ajhp070554] [PMID: 18593680]
[34]
Tanner T, Marks R. Delivering drugs by the transdermal route: review and comment. Skin Res Technol 2008; 14(3): 249-60.
[http://dx.doi.org/10.1111/j.1600-0846.2008.00316.x] [PMID: 19159369]
[35]
Zhou X, Hao Y, Yuan L, Pradhan S, Shrestha K, Pradhan O, et al. Nano-formulations for transdermal drug delivery: A review. Chin Chem Lett 2018; 29(12): 1713-24.
[http://dx.doi.org/10.1016/j.cclet.2018.10.037]
[36]
Md S, Haque S, Madheswaran T, et al. Lipid based nanocarriers system for topical delivery of photosensitizers. Drug Discov Today 2017; 22(8): 1274-83.
[http://dx.doi.org/10.1016/j.drudis.2017.04.010] [PMID: 28456749]
[37]
Waters C. The development of the rotigotine transdermal patch. A historical perspective. Neurol Clin 2013; 31(3S): S37-50.
[38]
Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson’s disease. Naunyn Schmiedebergs Arch Pharmacol 2009; 379(1): 73-86.
[http://dx.doi.org/10.1007/s00210-008-0341-4] [PMID: 18704368]
[39]
Senek M, Nyholm D. Continuous drug delivery in Parkinson’s disease. CNS Drugs 2014; 28(1): 19-27.
[http://dx.doi.org/10.1007/s40263-013-0127-1] [PMID: 24323838]
[40]
Elshoff JP, Cawello W, Andreas JO, Mathy FX, Braun M. An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson’s disease and restless legs syndrome. Drugs 2015; 75(5): 487-501.
[http://dx.doi.org/10.1007/s40265-015-0377-y] [PMID: 25795100]
[41]
Review S, Angeles LAL, Group AM. FDA Approves Neupro for Restless Legs Syndrome 2012; 1-2.
[42]
McAfee DA, Hadgraft J, Lane ME. Rotigotine: the first new chemical entity for transdermal drug delivery. Eur J Pharm Biopharm 2014; 88(3): 586-93.
[http://dx.doi.org/10.1016/j.ejpb.2014.08.007] [PMID: 25173087]
[43]
Toro BEC. New treatment options for the management of restless leg syndrome. J Neurosci Nurs 2014; 46(4): 227-32.
[http://dx.doi.org/10.1097/JNN.0000000000000068] [PMID: 24992148]
[44]
Oldfield V, Keating GM, Perry CM. Rasagiline: A Review of its Use in the Management of Parkinson’s Disease 2007; 67(12): 1725-47.
[http://dx.doi.org/10.1007/BF03257475]
[45]
Chaudhuri KR. Crystallisation within transdermal rotigotine patch: is there cause for concern? Expert Opin Drug Deliv 2008; 5(11): 1169-71.
[http://dx.doi.org/10.1517/17425240802500870] [PMID: 18976128]
[46]
Rietveld IB, Céolin R. Rotigotine: Unexpected Polymorphism with Predictable Overall Monotropic Behavior. J Pharm Sci 2015; 104(12): 4117-22.
[http://dx.doi.org/10.1002/jps.24626] [PMID: 26343810]
[47]
Elshoff J-P, Timmermann L, Schmid M, et al. Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Curr Med Res Opin 2013; 29(12): 1657-62.
[http://dx.doi.org/10.1185/03007995.2013.841666] [PMID: 24006953]
[48]
Antonini A, Bernardi L, Calandrella D, Mancini F, Plebani M. Rotigotine transdermal patch in the management of Parkinson’s disease (PD) and its night-time use for PD-related sleep disorders. Funct Neurol 2010; 25(1): 21-5.
[PMID: 20626993]
[49]
Gannu R, Palem CR, Yamsani VV, Yamsani SK, Yamsani MR. Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: formulation optimization, ex vivo and in vivo characterization. Int J Pharm 2010; 388(1-2): 231-41.
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.050] [PMID: 20060457]
[50]
Salimi A, Sharif Makhmal Zadeh B, Moghimipour E. Preparation and characterization of cyanocobalamin (vit B12) microemulsion properties and structure for topical and transdermal application. Iran J Basic Med Sci 2013; 16(7): 865-72.
[PMID: 23997918]
[51]
Wang Z, Mu HJ, Zhang XM, et al. Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies. Int J Nanomedicine 2015; 10: 633-44.
[PMID: 25609965]
[52]
Miyake MM, Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy 2015; 29(2): 124-7.
[http://dx.doi.org/10.2500/ajra.2015.29.4149] [PMID: 25785753]
[53]
Hanson LR, Frey WH II. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci 2008; 9(3): S5.
[http://dx.doi.org/10.1186/1471-2202-9-S3-S5]
[54]
Md S, Bhattmisra SK, Zeeshan F, Shahzad N, Mujtaba MA, Srikanth Meka V, et al. Nano-carrier enabled drug delivery systems for nose to brain targeting for the treatment of neurodegenerative disorders. J Drug Deliv Sci Technol 2018; 43: 295-310.
[http://dx.doi.org/10.1016/j.jddst.2017.09.022]
[55]
Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv 2013; 10(7): 957-72.
[http://dx.doi.org/10.1517/17425247.2013.790887] [PMID: 23586809]
[56]
Grassin-Delyle S, Buenestado A, Naline E, et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther 2012; 134(3): 366-79.
[http://dx.doi.org/10.1016/j.pharmthera.2012.03.003] [PMID: 22465159]
[57]
Md S, Mustafa G, Baboota S, Ali J. Nanoneurotherapeutics approach intended for direct nose to brain delivery. Drug Dev Ind Pharm 2015; 41(12): 1922-34.
[http://dx.doi.org/10.3109/03639045.2015.1052081] [PMID: 26057769]
[58]
Md S, Alhakamy NA, Aldawsari HM, Asfour HZ. Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery. Brain Sci 2019; 9(10): 275.
[http://dx.doi.org/10.3390/brainsci9100275] [PMID: 31618942]
[59]
Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv 2014; 21(2): 75-86.
[http://dx.doi.org/10.3109/10717544.2013.838713] [PMID: 24102636]
[60]
Mistry A, Stolnik S, Illum L. Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 2009; 379(1): 146-57.
[http://dx.doi.org/10.1016/j.ijpharm.2009.06.019] [PMID: 19555750]
[61]
Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 2013; 3(1): 42-62.
[http://dx.doi.org/10.1007/s13346-012-0108-9] [PMID: 23316447]
[62]
Upadhyay S, Parikh A, Joshi P, Upadhyay UM, Chotai NP. Intranasal drug delivery system- A glimpse to become maestro. J Appl Pharm Sci 2011; 1(3): 34-44.
[63]
Gomes MJ, Neves Jd, Sarmento B. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system. Int J Nanomedicine 2014; 9(1): 1757-69.
[PMID: 24741312]
[64]
Ali J, Ali M, Baboota S, et al. Potential of nanoparticulate drug delivery systems by intranasal administration. Curr Pharm Des 2010; 16(14): 1644-53.
[http://dx.doi.org/10.2174/138161210791164108] [PMID: 20210751]
[65]
Verma A, Stellacci F. Effect of surface properties on nanoparticle-cell interactions. Small 2010; 6(1): 12-21.
[http://dx.doi.org/10.1002/smll.200901158] [PMID: 19844908]
[66]
Ward PP, Uribe-Luna S, Conneely OM. Lactoferrin and host defense. Biochem Cell Biol 2002; 80(1): 95-102.
[http://dx.doi.org/10.1139/o01-214] [PMID: 11908649]
[67]
Kumar P, Lakshmi YS, C B, Golla K, Kondapi AK. Improved safety, bioavailability and pharmacokinetics of Zidovudine through lactoferrin nanoparticles during oral administration in rats. PLoS One 2015; 10(10)e0140399
[http://dx.doi.org/10.1371/journal.pone.0140399] [PMID: 26461917]
[68]
Yan X, Xu L, Bi C, Duan D, Chu L, Yu X, et al. Lactoferrinmodified rotigotine nanoparticles for enhanced nose-to-brain delivery : LESA-MS / MS- based drug biodistribution , pharmacodynamics and neuroprotective effects 2018; 272-81.
[69]
Choudhury H, Zakaria NF, Tilang PA, et al. Formulation development and evaluation of rotigotine mucoadhesive nanoemulsion for intranasal delivery. J Drug Deliv Sci Technol 2019; 54101301
[http://dx.doi.org/10.1016/j.jddst.2019.101301]
[70]
Tzeyung AS, Md S, Bhattamisra SK, et al. Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery. Pharmaceutics 2019; 11(1): 26.
[http://dx.doi.org/10.3390/pharmaceutics11010026] [PMID: 30634665]
[71]
Wang A, Wang L, Sun K, Liu W, Sha C, Li Y. Preparation of rotigotine-loaded microspheres and their combination use with L-DOPA to modify dyskinesias in 6-OHDA-lesioned rats. Pharm Res 2012; 29(9): 2367-76.
[http://dx.doi.org/10.1007/s11095-012-0762-0] [PMID: 22549738]
[72]
Wang A, Liu Y, Liang R, et al. Preparation and evaluation of rotigotine-loaded implant for the treatment of Parkinson’s disease and its evolution study. Saudi Pharm J 2016; 24(3): 363-70.
[http://dx.doi.org/10.1016/j.jsps.2016.04.022] [PMID: 27275128]
[73]
Yu X, Yao JY, He J, Tian JW. Protection of MPTP-induced neuroinflammation and neurodegeneration by rotigotine-loaded microspheres. Life Sci 2015; 124: 136-43.
[http://dx.doi.org/10.1016/j.lfs.2015.01.014] [PMID: 25640758]
[74]
Evans TC, Gavrilovich E, Mihai RC, Isbasescu I. Easyg Llc. ( 12 ) Patent Application Publication ( 10 ) 2015; 2(15): 354. Pub . No .: US 2006 / 0222585 A1
[75]
Laffleur F, Wagner J, Barthelmes J. A potential tailor-made hyaluronic acid buccal delivery system comprising rotigotine for Parkinson’s disease? Future Med Chem 2015; 7(10): 1225-32.
[http://dx.doi.org/10.4155/fmc.15.66] [PMID: 26144261]
[76]
Degeneration A. ( 19 ) United States ( 12 ) Patent Application Publication ( 10 ) Pub N0 : US 2014 / 0178309 A1 2014; 1(19)
[77]
Rascol O, Zesiewicz T, Chaudhuri KR, et al. A randomized con- trolled exploratory pilot study to evaluate the effect of rotigotine transdermal patch on Parkinson’s disease-associated chronic pain. J Clin Pharmacol 2016; 56(7): 852-61.
[http://dx.doi.org/10.1002/jcph.678] [PMID: 26626320]
[78]
Antonini A, Bauer L, Dohin E, et al. Effects of rotigotine transdermal patch in patients with Parkinson’s disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial. Eur J Neurol 2015; 22(10): 1400-7.
[http://dx.doi.org/10.1111/ene.12757] [PMID: 26095948]
[79]
Chung SJ, Asgharnejad M, Bauer L, Ramirez F, Jeon B. Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson’s disease. Expert Opin Pharmacother 2016; 17(11): 1453-61.
[http://dx.doi.org/10.1080/14656566.2016.1202917] [PMID: 27322571]
[80]
A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol 2003; 60(12): 1721-8.
[http://dx.doi.org/10.1001/archneur.60.12.1721] [PMID: 14676046]
[81]
Jankovic J, Watts RL, Martin W, Boroojerdi B. Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease. Arch Neurol 2007; 64(5): 676-82.
[http://dx.doi.org/10.1001/archneur.64.5.676] [PMID: 17502466]
[82]
Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease [published correction appears in Neurology 2007; 69(6): 617.
[83]
Zhang ZX, Shang HF, Hu X, et al. Rotigotine transdermal patch in Chinese patients with early Parkinson’s disease: A randomized, double-blind, placebo-controlled pivotal study. Parkinsonism Relat Disord 2016; 28: 49-55.
[http://dx.doi.org/10.1016/j.parkreldis.2016.04.022] [PMID: 27172830]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 19
Year: 2020
Published on: 17 June, 2020
Page: [2222 - 2232]
Pages: 11
DOI: 10.2174/1381612826666200316154300
Price: $65

Article Metrics

PDF: 30
HTML: 5