To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.
This article has been cited by other articles:
LeWitt, P. A.
(2008). Levodopa for the Treatment of Parkinson's Disease. NEJM
359: 2468-2476
[Full Text]
Gunzler, S. A., Koudelka, C., Carlson, N. E., Pavel, M., Nutt, J. G.
(2008). Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study. Arch Neurol
65: 193-198
[Abstract][Full Text]
Anderson, V. C., Burchiel, K. J., Hogarth, P., Favre, J., Hammerstad, J. P.
(2005). Pallidal vs Subthalamic Nucleus Deep Brain Stimulation in Parkinson Disease. Arch Neurol
62: 554-560
[Abstract][Full Text]
Adler, C. H.
(2002). Relevance of motor complications in Parkinson's disease. Neurology
58: S51-56
[Abstract][Full Text]
Koller, W. C.
(2002). Treatment of early Parkinson's disease. Neurology
58: S79-86
[Abstract][Full Text]
Nutt, J.G., Rufener, S.L., Carter, J.H., Anderson, V.C., Pahwa, R., Hammerstad, J.P., Burchiel, K.J.
(2001). Interactions between deep brain stimulation and levodopa in Parkinson's disease. Neurology
57: 1835-1842
[Abstract][Full Text]
Olanow, C. W., Watts, R. L., Koller, W. C.
(2001). An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment. Neurology
56: S1-S88
[Full Text]
Nutt, J. G., Nygaard, T. G.
(2001). Response to Levodopa Treatment in Dopa-Responsive Dystonia. Arch Neurol
58: 905-910
[Abstract][Full Text]
Manson, A. J., Hanagasi, H., Turner, K., Patsalos, P. N., Carey, P., Ratnaraj, N., Lees, A. J.
(2001). Intravenous apomorphine therapy in Parkinson's disease: Clinical and pharmacokinetic observations. Brain
124: 331-340
[Abstract][Full Text]
Münchau, A, Bhatia, K P
(2000). Pharmacological treatment of Parkinson's disease. Postgrad. Med. J.
76: 602-610
[Full Text]
Nutt, J. G., Carter, J. H.
(2000). Apomorphine can sustain the long-duration response to L-DOPA in fluctuating PD. Neurology
54: 247-247
[Abstract][Full Text]
Pietz, K., Hagell, P., Odin, P.
(1998). Subcutaneous apomorphine in late stage Parkinson's disease: a long term follow up. J. Neurol. Neurosurg. Psychiatry
65: 709-716
[Abstract][Full Text]
Quinn, N.
(1995). Fortnightly Review: Drug treatment of Parkinson's disease. BMJ
310: 575-579
[Abstract][Full Text]
Ahlskog, J. E., Muenter, M. D., Maraganore, D. M., Matsumoto, J. Y., Lieberman, A., Wright, K. F., Wheeler, K.
(1994). Fluctuating Parkinson's Disease: Treatment With the Eong-Acting Dopamine Agonist Cabergoline. Arch Neurol
51: 1236-1241
[Abstract]
Nutt, J. G., Woodward, W. R., Carter, J. H., Gancher, S. T.
(1992). Effect of Long-term Therapy on the Pharmacodynamics of Levodopa: Relation to On-Off Phenomenon. Arch Neurol
49: 1123-1130
[Abstract]
Karstaedt, P. J., Pincus, J. H.
(1992). Protein Redistribution Diet Remains Effective in Patients With Fluctuating Parkinsonism. Arch Neurol
49: 149-151
[Abstract]
Karstaedt, P. J., Pincus, J. H., Coughlin, S. S.
(1991). Standard and Controlled-Release Levodopa/Carbidopa in Patients With Fluctuating Parkinson's Disease on a Protein Redistribution Diet: A Preliminary Report. Arch Neurol
48: 402-405
[Abstract]
Hutton, J. T., Albrecht, J. W., Roman, G. C., Kopetzky, M. T.
(1988). Prolonged Serum Levodopa Levels With Controlled-Release Carbidopa-Levodopa in the Treatment of Parkinson's Disease. Arch Neurol
45: 55-57
[Abstract]
Kurlan, R.
(1987). Dietary Therapy for Motor Fluctuations in Parkinson's Disease. Arch Neurol
44: 1119-1121
[Abstract]
Juncos, J. L., Fabbrini, G., Mouradian, M. M., Serrati, C., Chase, T. N.
(1987). Dietary Influences on the Antiparkinsonian Response to Levodopa. Arch Neurol
44: 1003-1005
[Abstract]
Pincus, J. H., Barry, K. M.
(1987). Plasma Levels of Amino Acids Correlate With Motor Fluctuations in Parkinsonism. Arch Neurol
44: 1006-1009
[Abstract]
Juncos, J. L., Fabbrini, G., Mouradian, M. M., Chase, T. N.
(1987). Controlled Release Levodopa-Carbidopa (CR-5) in the Management of Parkinsonian Motor Fluctuations. Arch Neurol
44: 1010-1012
[Abstract]
Pincus, J. H., Barry, K.
(1987). Influence of Dietary Protein on Motor Fluctuations in Parkinson's Disease. Arch Neurol
44: 270-272
[Abstract]
Melamed, E.
(1986). Initiation of Levodopa Therapy in Parkinsonian Patients Should Be Delayed Until the Advanced Stages of the Disease. Arch Neurol
43: 402-405
[Abstract]
Previous
