Skip to main content
Log in

Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Motor performance of five patients with advanced Parkinson's disease was investigated during their optimum oral therapy (conventional tablets and/or depot capsules) and during a continuous duodenal infusion of levodopa. Due to the low water solubility of the drug, conventional tablets of levodopa + carbidopa (Sinemet®) were milled and dispersed in a 1.8% aqueous methylcellulose solution. The dispersion was delivered nasoduodenally by a portable pump. The effect of levodopa in the two dosing regimens was estimated optico-electronically every 15 min and was also evaluated from videorecordings every 30 min and plasma levels of levodopa was regularly measured. Each dosage regimen the was studied twice, at a 2–4 day interval.

Duodenal infusion improved motor function in all five patients and the fluctuations were reduced when compared to the oral therapy. Variation in plasma levodopa concentrations was 3–10 fold during oral therapy, while during the infusion a stable concentration was obtained. The therapeutic concentration varied from 0.3–3 μg ml−1 between patients. The relative bioavailability of levodopa in the solid preparation compared to the dispersion was in all patients 100%.

Our results encourage further development of a duodenal infusion system with a levodopa dispersion for clinical use in parkinsonian patients who show severe fluctuation.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Bredberg E, Tedroff J, Aquilonius S-M, Paalzow L (1990) Pharmacokinetics and effects of levodopa in advanced Parkinson's disease. Eur J Clin Pharmacol 39: 385–389

    Google Scholar 

  • Cedarbaum JM, Kutt H, McDowell FH (1989) A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). Neurology 39 [Suppl 2: 38–44

    Google Scholar 

  • Cedarbaum JM, Silvestri M, Kutt H (1990) Sustained enteral administration of levodopa increases and interrupted infusion decreases levodopa dose requirements. Neurology 40: 995–997

    Google Scholar 

  • Chase TN, Juncos JL, Serrati C, Fabbrini G, Bruno G (1986) Fluctuations in response to chronic levodopa therapy. Pathogenetic and therapeutic considerations. In: Yahr M, Bergman K (eds) Parkinson's disease. Raven Press, New York, pp 477–480

    Google Scholar 

  • Deleu D, Ebinger G, Michotte Y (1991) Clincial and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa. Eur J Clin Pharmacol 41: 453–458

    Google Scholar 

  • Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN (1988) (1988) Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, part 1. Ann Neurol 24: 366–371

    Google Scholar 

  • Hoehn MM, Yahr MD (1967) Parkinsonism: onset progression and mortality. Neurology 17: 427–442

    Google Scholar 

  • Ishimitsu T, Hirose S. (1985) Simultaneous assay of 3,4-dihydroxyphenylalanine, cathecholamines and O-methylated metabolites in human plasma using high-performance liquid chromatography. J Chromatogr 337: 239–248

    Google Scholar 

  • Jenner P, Boyce S, Marsden CD (1986) Effect of repeated 1-dopa administration on striatal dopamine receptor function in the rat. In: Fahn S, Marsden CD, Jenner P, Teychenne (eds) Recent developments in Parkinson's disease. Raven Press, New York, pp 189–203

    Google Scholar 

  • Johnels B, Ingvarsson PE, Thorselius M, Valls M, Steg G (1989) Disability profiles and objective quantitative assessment in Parkinson's disease. Acta Neurol Scand 79: 227–238

    Google Scholar 

  • Kurlan R, Rubin AJ, Miller C, Rivera-Calimlim L, Clarke A, Shoulson I (1986) Duodenal delivery of levodopa for on-off fluctuations in parkinsonism: preliminary observations. Ann Neurol 20: 262–265

    Google Scholar 

  • Kurlan R, Rothfield KP, Woodward WR, Nutt JG, Miller C, Lichter D, Shoulson I (1988a) Erratic gastric emptying of levodopa may cause “random” fluctuations of parkinsonian mobility. Neurology 38: 419–421

    Google Scholar 

  • Kurlan R, Nutt JG, Woodward WR, Rothfield KP, Lichter D, Miller C, Carter JH, Shoulson I (1988b) Duodenal and gastric delivery of levodopa in parkinsonism. Ann Neurol 23: 589–595

    Google Scholar 

  • Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL (1984a) The “on-off” phenomenon in Parkinson's disease: relation to levodopa absorption and transport. N Eng J Med 310: 483–484

    Google Scholar 

  • Nutt JG, Fellman JH (1984b) Pharmacokinetics of levodopa. Clin Neuropharmacol 7: 35–49

    Google Scholar 

  • Nutt JG, Woodward WR, Carter JH (1986) Clinical and biochemical studies with controlled-release levodopa/carbidopa. Neurology 36: 1206–1211

    Google Scholar 

  • Poewe WH, Lees AJ, Stern GM (1986) Treatment of motor fluctuations in Parkinson's disease with an oral sustained-release preparation of 1-dopa: clinical and pharmacokinetic observations. Clin Neuropharmacol 9: 430–439

    Google Scholar 

  • Quinn N, Parkes JD, Marsden CD (1984) Control of the on/off phenomenon by continuous intravenous infusion of levodopa. Neurology 34: 1131–1136

    Google Scholar 

  • Sage JI, Schuh L, Heikkila RE, Duvoisin RC (1988a) Continuous duodenal infusion of levodopa: plasma concentrations and motor fluctuations in Parkinson's disease. Clin Neuropharmacol 11: 36–44

    Google Scholar 

  • Sage JI, Trooskin S, Sonsalla PK, Heikkila R, Duvoisin RC (1988b) Long-term duodenal infusion of levodopa for motor fluctuations in parkinsonism. Ann Neurol 24: 87–89

    Google Scholar 

  • Shoulson I, Glaubiger GA, Chase TN (1975) On-off response: clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients. Neurology 24: 1144–1148

    Google Scholar 

  • Thorselius M, Johnels B, Ingvarsson PE, Valls M, Steg G (1989) Computer-aided analysis of a composite human movement. Technical Report No. 3: 89. Research Laboratory of Medical Electronics, Chalmers University of Technology, Göteborg, Sweden

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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 45, 117–122 (1993). https://doi.org/10.1007/BF00315491

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00315491

Key words

Navigation