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Does Levodopa Accelerate Parkinson’s Disease?

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Abstract

Therapeutic options for the treatment of Parkinson’s disease (PD) have expanded tremendously over the last 5 years, although levodopa remains the gold standard of therapy. A major therapeutic controversy has been the question of levodopa’s potential to cause toxic effects on nigrostriatal cells, thus potentiating the progression of the disease. The answer to that question will guide physicians in the timing of levodopa initiation and its dosage. The issue of levodopa toxicity was initially raised because of its potential to cause long term adverse effects (dyskinesias and motor fluctuations), which are not observed in untreated patients.

Levodopa-induced toxicity can be related to its potential to produce free radicals, which are known to be toxic to cells, in the process of its conversion to dopamine. In vitro data reveals some evidence of the toxic effect of levodopa although recent studies suggest that levodopa toxicity is dependent on its concentration and can be ameliorated in the presence of glial cells. In vivo data from healthy animals and humans does not convincingly demonstrate levodopa toxicity. There is no evidence of levodopa-induced neurotoxicity in patients with PD. Despite the absence of toxic effect in patients with PD, levodopa can cause long term complications like motor fluctuations and dyskinesias and should be used judiciously in the minimal clinically effective dose. In this article we review evidence for and against levodopa neurotoxicity and the implications of the ‘levodopa controversy’ on clinical practice.

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References

  1. Gibb WRG, Lees AJ. The significance of the Lewy body in the diagnosis of idiopathic Parkinson’s disease. Neuropathol Appl Neurobiol 1989; 15: 27–44

    Article  PubMed  CAS  Google Scholar 

  2. Ehringer H, Hornykiewicz O. Verteilung von noradrenalin und dopamin (3-hydroxytyramin) im gehirn des menschen und ihr verhalten bei erkrankungen des extrapyramidalen systems. Wien Klin Wochenschr 1960; 38: 1236–9

    CAS  Google Scholar 

  3. Cotzias GC, Papavasiliou PS. Therapeutic studies of parkinsonian patients: long-term effects of D,L- and L-dopa. Second International Congress of Neuro-ophthalmology: 1967 Sep 19; Montreal

  4. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modifications of parkinsonism. N Engl J Med 1967; 276: 374–9

    Article  PubMed  CAS  Google Scholar 

  5. Cotzias GC. Metabolic modification of some neurologic disorders. JAMA 1969; 210: 1255–62

    Article  PubMed  CAS  Google Scholar 

  6. Marsden CD, Barry PE, Parkes JD, et al. Treatment of Parkinson’s disease with levodopa combined with L-alpha-methyldopahydrazine, an inhibitor of extracerebral DOPA decarboxy lase. J Neurol Neurosurg Psychiatry 1973; 36: 10–4

    Article  PubMed  CAS  Google Scholar 

  7. Markham CH, Diamond SG, Treciokas LJ. Carbidopa in Parkinson’s disease and in nausea and vomiting of levodopa. Arch Neurol 1974; 31(3): 128–33

    Article  PubMed  CAS  Google Scholar 

  8. Martin WE, Tolosa ES, Loewenson RB, et al. The effects of combining carbidopa with levodopa for Parkinson’s disease. Genetics 1975; 30: 39–44

    CAS  Google Scholar 

  9. Barbeau A. Treatment of Parkinson’s disease with L-DOPA and Ro 4-4602: review and present status. In: Yahr MD, editor. Treatment of parkinsonism: the role of dopa decarboxylase inhibitors. New York: Raven Press, 1973: 173–98

    Google Scholar 

  10. Fahn S. Adverse effects of levodopa. In: Olanow CW, Lieberman AN, editors. The scientific basis for the treatment of Parkinson’s disease. Carnforth: Parthenon, 1992: 89–122

    Google Scholar 

  11. Fahn S. Is levodopa toxic? Neurology 1996; 47Suppl. 3: S184–95

    Article  PubMed  CAS  Google Scholar 

  12. Agid Y. Levodopa: is toxicity a myth? Neurology 1998; 50: 858–63

    Article  PubMed  CAS  Google Scholar 

  13. Blin J, Bonnet AM, Agid Y. Does levodopa aggravate Parkinson’s disease? Neurology 1988; 38: 1410–6

    Article  PubMed  CAS  Google Scholar 

  14. Cohen G. The pathobiology of Parkinson’s disease: biochemical aspects of dopamine neuron senescence. J Neural Transm 1983; Suppl. 19: 89–103

    Google Scholar 

  15. Mann DMA, Yates PO. Possible role of neuromelanin in the pathogenesis of Parkinson’s disease. Mech Ageing Dev 1983; 21: 193–203

    Article  PubMed  CAS  Google Scholar 

  16. Graham DG. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978; 14: 633–43

    PubMed  CAS  Google Scholar 

  17. Fahn S. The endogenous toxin hypothesis of the etiology of Parkinson’s disease and a pilot trial of high dosage antioxidants in an attempt to slow the progression of the illness. Ann N Y Acad Sci 1989; 570: 186–96

    Article  PubMed  CAS  Google Scholar 

  18. Olanow CW. Oxidation reactions in Parkinson’s disease. Neurology 1990; 40:Suppl. 13: 32–7

    PubMed  Google Scholar 

  19. Jenner P. Oxidative stress as acause of Parkinson’s disease. Acta Neurol Scand Suppl 1991; 136: 6–15

    Article  PubMed  CAS  Google Scholar 

  20. Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992; 32: 804–12

    Article  PubMed  CAS  Google Scholar 

  21. Mytilineou C, Han S-K, Cohen G. Toxic and protective effects of L-DOPA on mesencepahlic cell cultures. J Neurochem 1993; 61: 1470–8

    Article  PubMed  CAS  Google Scholar 

  22. Spina MB, Cohen G. Exposure of striatal synaptosomes to l-dopa elevates levels of oxidated glutathione. J Pharmacol Exp Ther 1988; 247: 502–7

    PubMed  CAS  Google Scholar 

  23. Spencer Smith T, Parker Jr WD, Bennett JP. L-DOPA increases nigral productions of hydroxyl radicals in vivo: potential L-DOPA toxicity? Neuroreport 1994; 5: 1009–11

    Article  Google Scholar 

  24. Spencer JPE, Jenner A, Aruoma OI, et al. Intense oxidative DNA damage promoted by L-DOPA and its metabolites: implications for neurodegenerative disease. FEBS Lett 1994; 353: 246–50

    Article  PubMed  CAS  Google Scholar 

  25. Poskanzer DC, Schwab RS. Cohort analysis of Parkinson’s syndrome: evidence for a single etiology related to subclinical infection about 1920. J Chronic Dis 1963; 16: 961–73

    Article  PubMed  CAS  Google Scholar 

  26. Ward CD, Duviosin RC, Ince SE, et al. Parkinson’s disease in 65 pairs of twins and in a set of quadruplets. Neurology 1983; 33: 815–24

    Article  PubMed  CAS  Google Scholar 

  27. Johnson WG, Hodge SE, Duvoisin R. Twin studies and the genetics of Parkinson’s disease: areappraisal. MovDisord 1990; 5: 187–94

    Article  CAS  Google Scholar 

  28. Rajput AH, Offord KP, Beard CM, et al. Epidemiology of parkinsonism: incidence, classification, and morality. Ann Neurol 1984; 16: 278–82

    Article  PubMed  CAS  Google Scholar 

  29. Tanner CM, Chen B, Wang W-Z, et al. Environmental factors in the etiology of Parkinson’s disease. Can J Neurol Sci 1987; 14: 419–23

    PubMed  CAS  Google Scholar 

  30. Stern M, Dulaney E, Gruber SB, et al. The epidemiology of Parkinson’s disease: a case-control study of young-onset and old-onset patients. Arch Neurol 1991; 48: 903–7

    Article  PubMed  CAS  Google Scholar 

  31. Calne DB, Langstem JW. Aetiology of Parkinson’s disease. Lancet 1983; II: 1457–9

    Article  Google Scholar 

  32. Jenner P, Shapira AHV, Marsden CD. New insights into the cause of Parkinson’s disease. Neurology 1992; 42: 2241–50

    Article  PubMed  CAS  Google Scholar 

  33. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993; 90: 7915–22

    Article  PubMed  CAS  Google Scholar 

  34. Simonian NA, Coyle JT. Oxidative stress in neurodegenerative diseases. Ann Rev Pharmacol Toxicol 1996; 36: 83–106

    Article  CAS  Google Scholar 

  35. Cross CE. Oxygen radicals and human disease. Ann Intern Med 1987; 107: 526–45

    PubMed  CAS  Google Scholar 

  36. Southorn PA, Powis G. Free radicals in medicine: 1. Chemical nature and biological reactions. Mayo Clin Proc 1988; 63: 381–9

    PubMed  CAS  Google Scholar 

  37. Oreland L. Monoamine oxidase, dopamine and Parkinson’s disease. Acta Neurol Scand 1991; 81Suppl. 136: 60–5

    Article  Google Scholar 

  38. Olanow CW, Youdim MHB. Iron and neurodegeneration: prospects for neuroprotection. In: Olanow CW, Jenner P, Youdim MHB, editors. Neurodegeneration and neuroprotection in Parkinson’s disease. London: Academic Press, 1996: 55–67

    Chapter  Google Scholar 

  39. Graham DG. On the origin and significance of neuromelanin. Arch Pathol Lab Med 1979; 103: 359–62

    PubMed  CAS  Google Scholar 

  40. Youdim MBH, Ben-Schachar D, Riederer P. Is Parkinson’s disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? Acta Neurol Scand 1989; 80Suppl. 126: 47–54

    Article  Google Scholar 

  41. Perry TL, Godin DV, Hansen S. Parkinson’s disease: a disorder due to nigral glutathione deficiency. Neurosci lett 1982; 33: 305–10

    Article  PubMed  CAS  Google Scholar 

  42. Sofic E, Lange KW, Jellinger K, et al. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 1992; 142: 128–30

    Article  PubMed  CAS  Google Scholar 

  43. Sian J, Dexter DT, Lees AJ, et al. Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 1994; 36: 348–55

    Article  PubMed  CAS  Google Scholar 

  44. Dexter DT, Sian J, Rose S, et al. Indices of oxidative stress and mitrochondrial function in individuals with incidental Lewy body disease. Ann Neurol 1994; 35: 38–44

    Article  PubMed  CAS  Google Scholar 

  45. Pardo B, Mena MA, de Yebenes JG. L-DOPA inhibits complex IV of the electron transport chain in catecholamine-rich human neuroblastoma NB69 cells. J Neurochem 1995; 64: 576–82

    Article  PubMed  CAS  Google Scholar 

  46. Ben-Shachar D, Zuk R, Glinka Y. Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 1995; 64: 718–23

    Article  PubMed  CAS  Google Scholar 

  47. Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by MPP+, a metabolite of the neurotoxin MPTP. Life Sci 1985; 36: 2503–8

    Article  PubMed  CAS  Google Scholar 

  48. Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease [letter]. Lancet 1989; I(8649): 1269

    Article  Google Scholar 

  49. Schapira AH, Mann VM, Cooper JM, et al. Anatomic and disease specificity of NADH CoQ reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 1990; 55: 2142–5

    Article  PubMed  CAS  Google Scholar 

  50. Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990; 54: 823–7

    Article  PubMed  CAS  Google Scholar 

  51. Predborski S, Jackson-Lewis V, Methune U, et al. Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity. Ann Neurol 1993; 34: 715–23

    Article  Google Scholar 

  52. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 1972; 26: 238–57

    Article  Google Scholar 

  53. Mochizuki H, Goto K, Mori H, et al. Histochemical detection of apoptosis in Parkinson’s disease. J Neurol Sci 1996; 2(137): 120–3

    Article  Google Scholar 

  54. Ziv I, Zilkha-Falb R, Offen D, et al. Levodopa induces apoptosis in cultured neuronal cells: a possible accelerator of nigrostriatal degeneration in Parkinson’s disease. Mov Disord 1997; 12: 17–23

    Article  PubMed  CAS  Google Scholar 

  55. Walkinshaw G, Waters CM. Induction of apoptosis in catecholaminergic PC 12 cells by L-DOPA: implications for the treatment of Parkinson’s disease. J Clin Invest 1995; 95: 2458–64

    Article  PubMed  CAS  Google Scholar 

  56. Ziv I, Offen D, Barzilay A, et al. The protooncogene Bcl-2, a novel cellular protective mechanism against dopamine toxicity: possible implications for Parkinson’s disease [abstract]. Neurology 1995; 45Suppl. 4: A279

    Google Scholar 

  57. Masserana JM, Gong L, Kulaga H, et al. Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system. Mol Pharmacol 1996; 50: 1309–15

    Google Scholar 

  58. Michel PP, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res 1990; 26: 428–35

    Article  PubMed  CAS  Google Scholar 

  59. Pardo B, Mena MA, Fahn S, et al. Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. Mov Discord 1993; 8: 278–84

    Article  CAS  Google Scholar 

  60. Pardo B, Mena MA, Casarejos MJ, et al. Toxic effects of L-dopa on mesencephalic cell cultures: protection with antioxidants. Brain Res 1995; 682: 133–43

    Article  PubMed  CAS  Google Scholar 

  61. Cedarbaum JM. Clinical pharmacokinetics of anti-parkinsonian drugs. Clin Phamacokinet 1987; 13: 141–78

    Article  CAS  Google Scholar 

  62. Pelton EW, Kimelberg HK, Shipherd SV, et al. Dopamine and norepinephrine uptake and metabolism by astroglial cells in culture. Life Sci 1981; 28: 1655–63

    Article  PubMed  CAS  Google Scholar 

  63. Desagher S, Glowinski J, Premont J. Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 1996; 16: 2553–62

    PubMed  CAS  Google Scholar 

  64. Mena MA, Casarejos MJ, Carazo A, et al. Glia conditioned medium protects fetal rat midbrain neurones in culture from L-dopa toxicity. Neuroreport 1996; 7: 441–5

    Article  PubMed  CAS  Google Scholar 

  65. Han SK, Mytilineou C, Cohen G. L-dopa up-regulates glutathione and protects mesencephalic cultures against oxidative stress. J Neurochem 1996; 66: 501–10

    Article  PubMed  CAS  Google Scholar 

  66. Mena MA, Davila V, Sulzer D. Neurotrophic effects of L-dopa in postnatal midbrain dopamine/cortical astrocyte cocultures. J Neurochem 1997; 69: 1398–408

    Article  PubMed  CAS  Google Scholar 

  67. Perry TL, Yong VW, Ito M, et al. Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of L-DOPA and carbidopa chronically. J Neurochem 1984; 43: 990–3

    Article  PubMed  CAS  Google Scholar 

  68. Cotzias GC, Miller ST, Tang LC, et al. Levodopa, fertility, and longevity. Science 1977; 196: 549–51

    Article  PubMed  CAS  Google Scholar 

  69. Hefti F, Melamed E, Bhawan J, et al. Long-term administration of L-DOPA does not damage dopaminergic neurons in the mouse. Neurology 1981; 31: 1194–5

    Article  CAS  Google Scholar 

  70. Melemed E, Rosenthal J. Can chronic levodopa therapy accelerate degeneration of dopaminergic neurons and progression of Parkinson’s disease? In: Nagtsu T, Fisher A, Yoshida M, editors. Basic, clinical, and therapeutic aspects of Alzheimer’s and Parkinson’s diseases. New York: Plenum Press, 1990: 253–6

    Chapter  Google Scholar 

  71. Loeffler DA, DeMaggio AJ, Juneau PL, et al. Effects of enhanced striatal dopamine turnover in vivo on glutathione oxidation. Clin Neuropharmacol 1994; 17: 370–9

    Article  PubMed  CAS  Google Scholar 

  72. Steece-Collier K, Yurek DM, Collier TJ, et al. Chronic levodopa impairs morphological development of grafted embryonic dopamine neurons. Exp Neurol 1990; 110: 201–8

    Article  PubMed  CAS  Google Scholar 

  73. Steece-Collier K, Yurek DM, Collier TJ, et al. The detrimental effect of levodopa on behavioral efficacy of fetal dopamine neuron grafts in rats is reversible following prolonged withdraw of chronic dosing. Brain Res 1995; 676: 404–8

    Article  PubMed  CAS  Google Scholar 

  74. Blunt SB, Jenner P, Marsden CD. Suppressive effect of L-DOPA on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine. Mov Disord 1993; 8: 129–33

    Article  PubMed  CAS  Google Scholar 

  75. Murer MG, Dziwczapolsik G, Menalled LB, et al. Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery in rats with moderate nigrostriatal lesions. Ann Neurol 1998; 43: 561–75

    Article  PubMed  CAS  Google Scholar 

  76. Quinn N, Parkes D, Janoto J, et al. Preservation of the substantia nigra and locus ceruleus in a patient receiving levodopa plus decarboxylase inhibitor over a four-year period. Mov Disord 1986; 1: 65–8

    Article  PubMed  CAS  Google Scholar 

  77. Rajput AH, Fenton ME, Dhand A. Is levodopa toxic to nondegenerating substantia nigra cells? Clinical evidence [abstract]. Neurology 1996; 46 Suppl.: A371

    Google Scholar 

  78. Rajput AH, Fenton ME, Birdi S, et al. Is levodopa toxic to human substantia nigra? Mov Disord 1997; 12: 634–8

    Article  PubMed  CAS  Google Scholar 

  79. Yahr MD, Wolf A, Antunes JL, et al. Autopsy findings in parkinsonism following treatment with levodopa. Neurology 1970; 6 Suppl.: 55–6

    Google Scholar 

  80. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967; 17: 427–42

    Article  PubMed  CAS  Google Scholar 

  81. Yahr MD. Evaluation of long-term therapy in Parkinson’s disease: mortality and therapeutic efficacy. In: Birkmayer W, Hornykiewicz O, editors. Advances in parkinsonism. Basel: Editiones Roche, 1976: 444–5

    Google Scholar 

  82. Hoehn MMM. Parkinsonism treated with levodopa: progression and mortality. J Neural Transm 1983; 19 Suppl.: 253–64

    Google Scholar 

  83. Scigliano G, Musicco M, Soliveri P, et al. Mortality associated with early and late levodopa therapy initiation in Parkinson’s disease. Neurology 1990; 40: 265–9

    Article  PubMed  CAS  Google Scholar 

  84. Clarke CE. Does levodopa therapy delay death in Parkinson’s disease? A review of the evidence. Mov Disord 1995; 10: 250–6

    Article  PubMed  CAS  Google Scholar 

  85. Louis ED, Marder K, Cote L, et al. Age at death is significantly younger in patients with Parkinson’s disease who have dementia and severe extrapyramidal signs [abstract]. Neurology 1996; 46: A377

    Article  Google Scholar 

  86. Kordower JH, Freeman TB, Snow BJ, et al. Neuropathological evidence of graft survival and striatal reinnvervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med 1995; 332: 1118–24

    Article  PubMed  CAS  Google Scholar 

  87. Waters CH. Managing the late complications of Parkinson’s disease. Neurology 1997; 49Suppl. 1: S49–57

    Article  PubMed  CAS  Google Scholar 

  88. Lesser RP, Fahn S, Snider SR, et al. Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29: 1253–60

    Article  PubMed  CAS  Google Scholar 

  89. Olanow CW. Arationale for dopamine agonists as primary therapy for Parkinson’s disease. Can J Neurol Sci 1992; 19: 108–12

    PubMed  CAS  Google Scholar 

  90. Caraceni T, Scigliano G, Mussico M. The occurrence of motor fluctuations in parkinsonian patients treated long-term with levodopa: role of early treatment and disease progression. Neurology 1991; 41: 380–4

    Article  PubMed  CAS  Google Scholar 

  91. Mouradian MM, Heuser DE, Baronti F, et al. Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson’s disease. Ann Neurol 1990; 27: 18–23

    Article  PubMed  CAS  Google Scholar 

  92. Rinne UK. Dopamine agonists in the treatment of Parkinson’s disease. In: Rinne UK, Yanagisawa N, editors. Controversies in treatment of Parkinson’s disease. Tokyo: PMSI, 1992: 49–60

    Google Scholar 

  93. Standaert DG, Stern MB. Update on the management of Parkinson’s disease. Med Clin North Am 1993; 77: 169–81

    PubMed  CAS  Google Scholar 

  94. Rascol A, Guiraud-Chaumeil B, Montrastruc JL, et al. Long-term treatment of Parkinson’s disease with bromocriptine. J Neurol Neurosurg Psychiatry 1979; 42: 143–50

    Article  PubMed  CAS  Google Scholar 

  95. Kurth MC, Tetrad JW, Tanner CM, et al. Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa cabidopa in Parkinson’s disease patients with on-off fluctuations. Neurology 1993; 43: 1698–703

    Article  PubMed  CAS  Google Scholar 

  96. Bredberg E, Nilsson D, Johansson K, et al. Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson’s disease. Eur J Clin Pharmacol 1993; 45: 117–22

    Article  PubMed  CAS  Google Scholar 

  97. Roberts JW, Cora-Locatelli G, Bravi D, et al. Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonism patients. Neurology 1994; 44: 2685–8

    Google Scholar 

  98. Mannisto PT, Kaakkola S. Rationale for selective COMT inhibitors as adjuncts in the drug treatment of Parkinson’s disease. Pharmacol Toxicol 1990; 66: 317–23

    Article  PubMed  CAS  Google Scholar 

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  1. University of Pennsylvania School of Medicine, Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA

    Tanya Simuni & Matthew B. Stern

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Simuni, T., Stern, M.B. Does Levodopa Accelerate Parkinson’s Disease?. Drugs & Aging 14, 399–408 (1999). https://doi.org/10.2165/00002512-199914060-00001

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