Impaired absorption of oral levodopa: a major cause for response fluctuations in Parkinson's disease
- PMID:9007159
Impaired absorption of oral levodopa: a major cause for response fluctuations in Parkinson's disease
Abstract
Most patients with Parkinson's disease develop response fluctuations after several years of chronic treatment with levodopa. Accumulating evidence suggest that pharmacokinetic mechanisms are the cause of some subtypes of response fluctuations, especially the "delayed-on" and "no-on" phenomena. Evaluation of gastric emptying in Parkinson patients with and without response fluctuations revealed that those with fluctuations had a significant delay in gastric emptying compared to patients without fluctuations. Treatment with cisapride, a prokinetic drug, causes amelioration of these fluctuations. The optimal solution is to bypass the stomach completely and deliver levodopa parenterally. This was done by levodopa ethylester injections, which reduced latency to "on" and prolonged "on" duration in patients with severe response fluctuations. These data emphasize the role of the stomach as one of the causes for deterioration in Parkinson's disease.
Similar articles
- Effect of cisapride on response fluctuations in Parkinson's disease.Djaldetti R, Koren M, Ziv I, Achiron A, Melamed E.Djaldetti R, et al.Mov Disord. 1995 Jan;10(1):81-4. doi: 10.1002/mds.870100113.Mov Disord. 1995.PMID:7885359Clinical Trial.
- Irregular gastrointestinal drug absorption in Parkinson's disease.Nyholm D, Lennernäs H.Nyholm D, et al.Expert Opin Drug Metab Toxicol. 2008 Feb;4(2):193-203. doi: 10.1517/17425255.4.2.193.Expert Opin Drug Metab Toxicol. 2008.PMID:18248312Review.
- Levodopa ethylester: a novel rescue therapy for response fluctuations in Parkinson's disease.Djaldetti R, Melamed E.Djaldetti R, et al.Ann Neurol. 1996 Mar;39(3):400-4. doi: 10.1002/ana.410390321.Ann Neurol. 1996.PMID:8602763Clinical Trial.
- Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses.Okereke CS, Kirby L, Kumar D, Cullen EI, Pratt RD, Hahne WA.Okereke CS, et al.Br J Clin Pharmacol. 2004 Nov;58 Suppl 1(Suppl 1):41-9. doi: 10.1111/j.1365-2125.2004.01799.x.Br J Clin Pharmacol. 2004.PMID:15496222Free PMC article.Clinical Trial.
- [Optimisation of treatment of Parkinson's disease with levodopa].Białecka M, Adamiak U, Gawrońska-Szklarz B.Białecka M, et al.Neurol Neurochir Pol. 2009 Sep-Oct;43(5):446-59.Neurol Neurochir Pol. 2009.PMID:20054747Review.Polish.
Cited by
- Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease.Anderson G, Noorian AR, Taylor G, Anitha M, Bernhard D, Srinivasan S, Greene JG.Anderson G, et al.Exp Neurol. 2007 Sep;207(1):4-12. doi: 10.1016/j.expneurol.2007.05.010. Epub 2007 May 18.Exp Neurol. 2007.PMID:17586496Free PMC article.
- Early identification of drug-induced impairment of gastric emptying through physiologically based pharmacokinetic (PBPK) simulation of plasma concentration-time profiles in rat.Peters SA, Hultin L.Peters SA, et al.J Pharmacokinet Pharmacodyn. 2008 Feb;35(1):1-30. doi: 10.1007/s10928-007-9073-1. Epub 2007 Oct 26.J Pharmacokinet Pharmacodyn. 2008.PMID:17963025
- Ghrelin prevents levodopa-induced inhibition of gastric emptying and increases circulating levodopa in fasted rats.Wang L, Murphy NP, Stengel A, Goebel-Stengel M, St Pierre DH, Maidment NT, Taché Y.Wang L, et al.Neurogastroenterol Motil. 2012 May;24(5):e235-45. doi: 10.1111/j.1365-2982.2012.01904.x. Epub 2012 Mar 23.Neurogastroenterol Motil. 2012.PMID:22443313Free PMC article.
- Parkinson's disease is not associated with gastrointestinal myenteric ganglion neuron loss.Annerino DM, Arshad S, Taylor GM, Adler CH, Beach TG, Greene JG.Annerino DM, et al.Acta Neuropathol. 2012 Nov;124(5):665-80. doi: 10.1007/s00401-012-1040-2. Epub 2012 Sep 2.Acta Neuropathol. 2012.PMID:22941241Free PMC article.
- Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease.Greene JG, Noorian AR, Srinivasan S.Greene JG, et al.Exp Neurol. 2009 Jul;218(1):154-61. doi: 10.1016/j.expneurol.2009.04.023. Epub 2009 May 3.Exp Neurol. 2009.PMID:19409896Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Medical