Skip to main content
Log in

Management of Parkinson Disease

Defining the Role of Ropinirole

  • Drugs In Disease Management
  • Published:
Disease Management & Health Outcomes

Abstract

Parkinson disease is a movement disorder caused by progressive dopaminergic neuron degeneration in the substantia nigra and characterized by four cardinal symptoms: resting tremor, bradykinesia, rigidity, and postural instability. Levodopa has been considered the first-choice intervention for Parkinson disease for more than three decades. However, up to 50–90% of levodopa-treated patients develop motor complications within 5–10 years of starting treatment. It is important, therefore, to delay the initiation and/or reduce the dosage requirements of levodopa. The non-ergoline dopamine agonist ropinirole (Requip®) is used as monotherapy or in combination with low-dose levodopa in patients with early disease, and as an adjunct to levodopa in patients with advanced Parkinson disease.

As an adjunct to levodopa therapy in patients with more advanced disease, ropinirole is generally more effective than bromocriptine and more effective than placebo. Ropinirole (with or without levodopa) is more effective than placebo and at least as effective as bromocriptine when administered as therapy for early Parkinson disease. It reduces the risk of dyskinesia relative to levodopa and maintains long-term control of the underlying disease symptoms, factors that are associated with improved functional ability. Ropinirole reduced the loss of putamen dopamine storage capacity compared with levodopa in a functional imaging study. However, it was unclear whether this resulted from any neuroprotective activity of ropinirole; further research is required to identify any clinically important neuroprotective activity of dopamine agonists. Ropinirole has a tolerability profile generally similar to that of bromocriptine and levodopa when used as monotherapy. In common with all dopaminergic agents, ropinirole has been linked with sedation and unintended sleep episodes; however, these effects may also result from the underlying disease process in patients with Parkinson disease.

Only limited data are available from pharmacoeconomic evaluations of ropinirole. Nevertheless, a cost-minimization analysis indicates that, from a societal viewpoint in Canada, ropinirole is cost saving relative to treatment with levodopa plus a dopa decarboxylase inhibitor in patients with early Parkinson disease. Further economic and quality-of-life assessments of ropinirole are required, particularly comparisons with other dopamine agonists and antiparkinsonian interventions.

In conclusion, ropinirole is established as an adjunct to levodopa in advanced Parkinson disease, and as monotherapy or in combination with low-dose levodopa in early disease. It is in the setting of early Parkinson disease that ropinirole may see greatest expansion of its overall role in disease management programs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Fig. 1
Table II
Table III
Fig. 2
Table IV

Similar content being viewed by others

Notes

  1. Use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology 2001 Jun; 56 (11 Suppl. 5): 1–88

    Article  Google Scholar 

  2. Rubenstein LM, DeLeo A, Chrischilles EA. Economic and health-related quality of life considerations of new therapies in Parkinson’s disease. Pharmacoeconomics 2001; 19(7): 729–52

    Article  PubMed  CAS  Google Scholar 

  3. Hauser RA, Zesiewicz TA. Management of early Parkinson’s disease. Med Clin North Am 1999 Mar; 83(2): 393–414

    Article  PubMed  CAS  Google Scholar 

  4. Matheson AJ, Spencer CM. Ropinirole: a review of its use in the management of Parkinson’s disease. Drugs 2000 Jul; 60(1): 115–37

    Article  PubMed  CAS  Google Scholar 

  5. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson’s disease. Arch Neurol 1999 Jan; 56: 33–9

    Article  PubMed  CAS  Google Scholar 

  6. Hoehn MM. The natural history of Parkinson’s disease in the pre-levodopa and post- levodopa eras. Neurol Clin 1992 May; 10(2): 331–9

    PubMed  CAS  Google Scholar 

  7. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967 May; 17(5): 427–42

    Article  PubMed  CAS  Google Scholar 

  8. Kuhn W, Winkel R, Woitalla D, et al. High prevalence of parkinsonism after occupational exposure to lead-sulfate batteries. Neurology 1998 Jun; 50(6): 1885–6

    Article  PubMed  CAS  Google Scholar 

  9. Choi IS. Parkinsonism after carbon monoxide poisoning. Eur Neurol 2002; 48(1): 30–3

    Article  PubMed  Google Scholar 

  10. Gorell JM, Rybicki BA, Johnson CC, et al. Occupational metal exposures and the risk of Parkinson’s disease. Neuroepidemiology 1999; 18(6): 303–8

    Article  PubMed  CAS  Google Scholar 

  11. Kim Y, Kim JM, Kim JW, et al. Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: what does it mean? Mov Disord 2002; 17(3): 568–75

    Article  PubMed  CAS  Google Scholar 

  12. Gorell JM, Johnson CC, Rybicki BA, et al. The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998 May; 50(5): 1346–50

    Article  PubMed  CAS  Google Scholar 

  13. Marder K, Logroscino G, Alfaro B, et al. Environmental risk factors for Parkinson’s disease in an urban multiethnic community. Neurology 1998 Jan; 50(1): 279–81

    Article  PubMed  CAS  Google Scholar 

  14. Olanow CW. An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 1992; 32 Suppl.: S2–9

    Article  PubMed  CAS  Google Scholar 

  15. Gorell JM, Rybicki BA, Johnson CC, et al. Smoking and Parkinson’s disease: a dose-response relationship. Neurology 1999 Jan 1; 52(1): 115–9

    Article  PubMed  CAS  Google Scholar 

  16. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000; 283(20): 2674–9

    Article  PubMed  CAS  Google Scholar 

  17. Tanner CM, Ottman R, Goldman SM, et al. Parkinson disease in twins: an etiologic study. JAMA 1999 Jan 27; 281(4): 341–6

    Article  PubMed  CAS  Google Scholar 

  18. Richter G, Sonnenschein A, Grunewald T, et al. Novel mitochondrial DNA mutations in Parkinson’s disease. J Neural Transm 2002 May; 109: 721–9

    Article  PubMed  CAS  Google Scholar 

  19. Hristova AH, Koller WC. Early Parkinson’s disease: what is the best approach to treatment? Drugs Aging 2000 Sep; 17(3): 165–81

    Article  PubMed  CAS  Google Scholar 

  20. Early Parkinson’s disease: dopamine agonists have increasingly important role in symptom management. Drug Ther Perspect 2001 Aug 27; 17(17): 5–10

    Article  Google Scholar 

  21. Dodel RC, Berger K, Oertel WH. Health-related quality of life and healthcare utilisation in patients with Parkinson’s disease: impact of motor fluctuations and dyskinesias. Pharmacoeconomics 2001; 19(10): 1013–38

    Article  PubMed  CAS  Google Scholar 

  22. Iskedjian M, Einarson TR. Cost analysis of ropinirole versus levodopa in the treatment of Parkinson’s disease. Pharmacoeconomics 2003; 21(2): 115–27

    Article  PubMed  Google Scholar 

  23. Chio A, Magnani C, Schiffer D, et al. Prevalence of Parkinson’s disease in Northwestern Italy: comparison of tracer methodology and clinical ascertainment of cases. Mov Disord 1998; 13(3): 400–5

    Article  PubMed  CAS  Google Scholar 

  24. Kuopio AM, Marttila RJ, Helenius H, et al. Changing epidemiology of Parkinson’s disease in southwestern Finland. Neurology 1999 Jan 15; 52(2): 302–8

    Article  PubMed  CAS  Google Scholar 

  25. Wermuth L, Joensen P, Bunger N, et al. High prevalence of Parkinson’s disease in the Faroe Island. Neurology 1997; 49(2): 426–32

    Article  PubMed  CAS  Google Scholar 

  26. Melcon MO, Anderson DW, Vergara RH, et al. Prevalence of Parkinson’s disease in Junin, Buenos Aires Province, Argentina. Mov Disord 1997; 12(2): 197–205

    Article  PubMed  CAS  Google Scholar 

  27. Bower JH, Maraganore DM, McDonnell SK, et al. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976–1990. Neurology 1999 Apr 12; 52(6): 1214–20

    Article  PubMed  CAS  Google Scholar 

  28. Schrag A, Ben-Shlomo Y, Quinn NP. Cross sectional prevalence survey of idiopathic Parkinson’s disease and Parkinsonism in London. BMJ 2000 Jul 1; 321(7252): 21–2

    Article  PubMed  CAS  Google Scholar 

  29. Errea JM, Ara JR, Aibar C, et al. Prevalence of Parkinson’s disease in Lower Aragon, Spain. Mov Disord 1999; 14(4): 596–604

    Article  PubMed  CAS  Google Scholar 

  30. Montgomery JREB. Two advances in the management of Parkinson disease. Cleve Clin J Med 2002 Aug; 69(8): 639–43

    Article  PubMed  Google Scholar 

  31. Kuzel MD. Ropinirole: a dopamine agonist for the treatment of Parkinson’s disease. Am J Health Syst Pharm 1999 Feb 1; 56(3): 217–24

    PubMed  CAS  Google Scholar 

  32. Rubenstein LM, Chrischilles EA, Voelker MD. The impact of Parkinson’s disease on health status, health expenditures, and productivity. Estimates from the National Medical Expenditure Survey. Pharmacoeconomics 1997 Oct; 12(4): 486–98

    Article  PubMed  CAS  Google Scholar 

  33. Jenkinson C. Quality-of-life repercussions and costs of Parkinson’s disease [in French]. Dis Manage Health Outcomes 2001; 9(1): 11–9

    Article  Google Scholar 

  34. Whetten-Goldstein K, Sloan F, Kulas E, et al. The burden of Parkinson’s disease on society, family, and the individual. J Am Geriatr Soc 1997 Jul; 45(7): 844–9

    PubMed  CAS  Google Scholar 

  35. Siderowf AD, Holloway RG, Stern MB. Cost-effectiveness analysis in Parkinson’s disease: determining the value of interventions. Mov Disord 2000 May; 15: 439–45

    Article  PubMed  CAS  Google Scholar 

  36. LePen C, Wait S, Moutard-Martin F, et al. Cost of illness and disease severity in a cohort of French patients with Parkinson’s disease. Pharmacoeconomics 1999 Jul; 16(1): 59–69

    Article  PubMed  CAS  Google Scholar 

  37. Kurlan R, Clark S, Shoulson I, et al. Economic impact of protective therapy for early Parkinson’s disease [abstract no. P109]. Ann Neurol 1988 Jul; 24(1): 153

    Google Scholar 

  38. Djaldetti R, Melamed E. Management of response fluctuations: paractical guidelines. Neurology 1998 Aug; 51 (2 Suppl. 2): S36–40

    Article  PubMed  CAS  Google Scholar 

  39. Vidailhet M, Bonnet AM, Marconi R, et al. The phenomenology of L-dopa-induced dyskinesias in Parkinson’s disease. Mov Disord 1999; 14 Suppl. 1: 13–8

    PubMed  Google Scholar 

  40. Fahn S. The spectrum of levodopa-induced dyskinesias. Ann Neurol 2000; 47 Suppl. 1: S2–S11

    PubMed  CAS  Google Scholar 

  41. Koller WC. Levodopa in the treatment of Parkinson’s disease. Neurology 2000; 55 (11 Suppl. 4): S2–7; discussion S8-12

    PubMed  CAS  Google Scholar 

  42. Koller WC. Treatment of early Parkinson’s disease. Neurology 2002; 58 (4 Suppl. 1): S79–86

    Article  PubMed  CAS  Google Scholar 

  43. Dooley M, Markham A. Pramipexole: a review of its use in the management of early and advanced Parkinson’s disease. Drugs Aging 1998 Jun; 12(6): 495–514

    Article  PubMed  CAS  Google Scholar 

  44. Contin M, Riva R, Albani F, et al. Pharmacokinetic optimisation of dopamine receptor agonist therapy for Parkinson’s disease. CNS Drugs 2000 Dec; 14(6): 439–55

    Article  CAS  Google Scholar 

  45. Colosimo C, De Michele M. Motor fluctuations in Parkinson’s disease: pathophysiology and treatment. Eur J Neurol 1999 Jan; 6(1): 1–21

    Article  PubMed  CAS  Google Scholar 

  46. Le WD, Jankovic J. Are dopamine receptor agonists neuroprotective in Parkinson’s disease? Drugs Aging 2001; 18(6): 389–96

    Article  PubMed  CAS  Google Scholar 

  47. Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 2003 Jul; 54(1): 93–101

    Article  PubMed  CAS  Google Scholar 

  48. Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002 Apr 3; 287(13): 1653–61

    Article  Google Scholar 

  49. Schrag A, Keens J, Warner J. Ropinirole for the treatment of tremor in early Parkinson’s disease. Eur J Neurol 2002 May; 9(3): 253–7

    Article  PubMed  CAS  Google Scholar 

  50. Arle JE, Alterman RL. Surgical options in Parkinson’s disease. Med Clin North Am 1999 Mar; 83(2): 483–98

    Article  PubMed  CAS  Google Scholar 

  51. Hallett M, Litvan I. Evaluation of surgery for Parkinson’s disease: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The Task Force on Surgery for Parkinson’s Disease. Neurology 1999 Dec 10; 53(9): 1910–21

    Article  PubMed  CAS  Google Scholar 

  52. Lang AE. Surgery for Parkinson disease: a critical evaluation of the state of the art. Arch Neurol 2000 Aug; 57(8): 1118–25

    Article  PubMed  CAS  Google Scholar 

  53. Ropinirole hydrochloride. Mosby’s Drug Consult 2003, 2789-94

  54. Whone AL, Rakshi JS, Watts DJ, et al. Two trials demonstrating disease-slowing effects of ropinirole, compared with L-dopa, in early Parkinson’s disease [abstract no. P242]. Mov Disord 2002; 17 Suppl. 5: S85–6

    Google Scholar 

  55. Rascol O, Brooks DJ, Korczyn AD, et al. 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 May 18; 342(20): 1484–91

    Article  PubMed  CAS  Google Scholar 

  56. Korczyn AD, Brunt ER, Larsen JP, et al. A 3-year randomized trial of ropinirole and bromocriptine in early Parkinson’s disease. The 053 Study Group [erratum published in Neurology 1999 Sep 22; 53: 1162]. Neurology 1999 Jul 22; 53(2): 364–70

    Article  PubMed  CAS  Google Scholar 

  57. Sethi KD, O’Brien CF, Hammerstad JP, et al. Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Ropinirole Study Group. Arch Neurol 1998 Sep; 55(9): 1211–6

    Article  PubMed  CAS  Google Scholar 

  58. Brooks DJ, Abbott RJ, Lees AJ, et al. A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole dopaminergic therapy in Parkinson’s disease. Clin Neuropharmacol 1998; 21(2): 101–7

    PubMed  CAS  Google Scholar 

  59. Adler CH, Sethi KD, Hauser RA, et al. Ropinirole for the treatment of early Parkinson’s disease. The Ropinirole Study Group. Neurology 1997 Aug; 49(2): 393–9

    Article  PubMed  CAS  Google Scholar 

  60. Rascol O, Lees AJ, Senard JM, et al. Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson’s disease. Clin Neuropharmacol 1996 Jun; 19(3): 234–45

    Article  PubMed  CAS  Google Scholar 

  61. Lieberman A, Olanow CW, Sethi K, et al. A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease. Ropinirole Study Group [erratum in Neurology 1999 Jan 15; 52 (2): 435]. Neurology 1998 Oct; 51(4): 1057–62

    Article  PubMed  CAS  Google Scholar 

  62. Brunt ER, Brooks DJ, Korczyn AD, et al. A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson’s disease not optimally controlled by L-dopa. J Neural Transm 2002; 109(4): 489–502

    Article  PubMed  CAS  Google Scholar 

  63. Perez-Aharon J, Abbot RJ, Playfer JR, et al. Ropinirole, a placebo-controlled study of efficacy as adjunct therapy in parkinsonian patients not optimally controlled on L-dopa. Neurology 1994 Apr; 44 Suppl. 2: A244

    Google Scholar 

  64. Fabbrini G, Barbanti P, Rum A, et al. Combined levodopa test in the evaluation of efficacy of pergolide and ropinirole [abstract]. Mov Disord 1998; 13 Suppl. 2: 50

    Google Scholar 

  65. Im JH, Ha JH, Cho IS, et al. Ropinirole as an adjunct to levodopa in the treatment of Parkinson’s disease: a 16-week bromocriptine controlled study. J Neurol 2003; 250(1): 90–6

    Article  PubMed  Google Scholar 

  66. Gimenez-Roldan S, Esteban EM, Mateo D. Switching from bromocriptine to ropinirole in patients with advanced Parkinson’s disease: open label pilot responses to three different dose-ratios. Clin Neuropharmacol 2001; 24(6): 346–51

    Article  PubMed  CAS  Google Scholar 

  67. Canesi M, Antonini A, Mariani CB, et al. Overnight switch to ropinirole improves activities of daily living in Parkinson’s disease patients. Neurology 2000; 54 (7 Suppl. 3): A280

    Google Scholar 

  68. Korczyn AD, Thalamas C, Adler CH. Dosing with ropinirole in a clinical setting. Acta Neurol Scand 2002 Oct; 106(4): 200–4

    Article  PubMed  CAS  Google Scholar 

  69. Clarke CE, Deane KH. Ropinirole for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev 2000; (3): CD001516

  70. Brunt ER, Korczyn AD, Lieberman A, et al. The long-term efficacy of ropinirole as an adjunct to L-dopa. Neurology 1999; 52 Suppl. 2: A408–9

    Google Scholar 

  71. Clarke CE, Deane KH. Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev 2000; (3): CD001517

  72. Weiner WJ, Minagar A, Shulman LM. Ropinirole after pramipexole failure in advanced Parkinson’s disease [abstract no. W236]. Ann Neurol 1998 Sep; 44(3): 502

    Google Scholar 

  73. Inzelberg R, Carasso RL, Schechtman E, et al. A comparison of dopamine agonists and catechol-O-methyltransferase inhibitors in Parkinson’s disease. Clin Neuropharmacol 2000; 23(5): 262–6

    Article  PubMed  CAS  Google Scholar 

  74. Schrag AE, Brooks DJ, Brunt E, et al. The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson’s disease. Clin Neuropharmacol 1998; 21(3): 169–75

    PubMed  CAS  Google Scholar 

  75. Korczyn AD, Keens J, Oldham M, et al. The safety and efficacy of ropinirole as early therapy in elderly patients with Parkinson’s disease. Neurology 2000 Apr 11; 54 (7 Suppl. 3): A90

    Google Scholar 

  76. Fuell D, Gardiner D, Krieder MS. The effect of concomitant selegiline on Parkinson’s disease patients treated with ropinirole. Neurology 1998 Apr; 50 (4 Suppl. 4): A279

    Google Scholar 

  77. Stocchi F, Destee A. Co-administration of ropinirole and domperidone during rapid dose escalation of the dopamine agonist. Parkinsonism Relat Disord 1998; 4(4): 183–8

    Article  PubMed  CAS  Google Scholar 

  78. SmithKline Beecham Pharmaceuticals. Requip brand of ropinirole hydrochloride tablets. Prescribing information. 2001

  79. Chaudhuri KR, Pal S, Brefel-Courbon C. ’sleep attacks’ or ‘unintended sleep episodes’ occur with dopamine agonists: is this a class effect? Drug Saf 2002; 25(7): 473–83

    Article  PubMed  CAS  Google Scholar 

  80. Larsen JP, Tandberg E. Sleep disorders in patients with Parkinson’s disease: epidemiology and management. CNS Drugs 2001; 15(4): 267–75

    Article  PubMed  CAS  Google Scholar 

  81. Clarke CE, Vieregge P, Ziegler M, et al. The impact of L-Dopa-induced dyskinesias on patients’ quality of life in Parkinson’s disease: a prospective European study [abstract no. P06.109]. Neurology 2002; 58 (7 Suppl. 3): A469

    Google Scholar 

  82. Pechevis MR, Clarke CE, Vieregge M, et al. The impact of L-dopa-induced dyskinesia on direct health care and non-health care costs associated with patients with Parkinson’s disease: a prospective European study [abstract no. P340]. Mov Disord 2002; 17 Suppl. 5: S115

    Google Scholar 

  83. Shimbo T, Hira K, Takemura M, et al. Cost-effectiveness analysis of dopamine agonists in the treatment of Parkinson’s disease in Japan. Pharmacoeconomics 2001; 19(8): 875–86

    Article  PubMed  CAS  Google Scholar 

  84. Hoerger TJ, Bala MV, Rowland C, et al. Cost effectiveness of pramipexole in Parkinson’s disease in the US. Pharmacoeconomics 1998 Nov; 14(5): 541–57

    Article  PubMed  CAS  Google Scholar 

  85. Bhatia K, Brooks DJ, Burn DJ, et al. Guidelines for the management of Parkinson’s disease. Hosp Med 1998 Jun; 59(6): 469–80

    PubMed  CAS  Google Scholar 

  86. Olanow CW, Schapira AHV, Roth T, et al. Falling asleep at the wheel: motor vehicle mishaps in people taking pramipexole and ropinirole [letter]. Neurology 2000 Jan 11; 54(1): 274–7

    Article  PubMed  CAS  Google Scholar 

  87. American Sleep Disorders Association. International classificaction of sleep disorders revised: diagnostic and coding manual. Rochester (MN): American Sleep Disorders Association, 1997

    Google Scholar 

  88. Hauser RA, Gauger L, McDowell Anderson W, et al. Pramipexole-induced somnolence and episodes of daytime sleep. Mov Dis 2000; 15(4): 658–63

    Article  CAS  Google Scholar 

  89. Ebersbach G, Nordon J, Tracik F. Sleep attacks in Parkinson’s disease: polysomnographic recordings. Mov Disord 2000; 15 Suppl. 3: 89

    Google Scholar 

  90. Hobson DE, Lang AE, Martin WR, et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 2002; 287(4): 455–63

    Article  PubMed  Google Scholar 

  91. Clarke CE, Guttman M. Dopamine agonist monotherapy in Parkinson’s disease. Lancet 2002 Nov 30; 360: 1767–9

    Article  PubMed  CAS  Google Scholar 

  92. Morrish P. Is it time to abandon functional imaging in the study of neuroprotection? Mov Disord 2002 Mar; 17(2): 229–32

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David Murdoch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murdoch, D., Cheer, S.M. & Wagstaff, A.J. Management of Parkinson Disease. Dis-Manage-Health-Outcomes 12, 39–54 (2004). https://doi.org/10.2165/00115677-200412010-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00115677-200412010-00004

Keywords

Navigation