Pharmacokinetic studies with sustained-release formulations of levodopa in healthy volunteers
On the basis of the results of a large number of studies of the correlation between plasma levodopa levels and the occurrence of mobility disorders, it was concluded that side-effects such as dyskinesia, end-of-dose, peak-dose and on-off phenomena, which occur especially during levodopa long- term treatment of Parkinson patients, may be caused by fluctuations in the plasma levodopa levels. Some preliminary trials using sustained-release formulations were not up to expectations. Still, we studied the question of whether it might not be possible after all to obtain sustained plasma levodopa levels over prolonged periods of time with levodopa sustained-release (S. R.) formulations, without causing a high initial peak. For this purpose, we compared the pharmacokinetics of six different levodopa S. R. formulations with a standard preparation in two randomized cross-over trials in healthy male volunteers.
Although the levodopa S. R. formulations prolonged the time to peak blood levels in all cases, a plateau that was constant over a longer period of time could not be obtained. However, none of the S. R. preparations studied gave rise to a high initial peak of the plasma levodopa concentration. The levodopa concentrations had again returned to endogenous levels within no more than 8 hours of administration of all six levodopa S. R. formulations.
KeywordsLevodopa Dose Levodopa Concentration Plasma Levodopa Plasma Levodopa Concentration Levodopa Level
Unable to display preview. Download preview PDF.
- Gerlach M, Gebhardt B, Kuhn W, Przuntek H (1986) Die Abhängigkeit der Resorption des L-Dopa von Galenik und veränderter Magensaftsekretion des Parkinson-Patienten. In: Fischer PA (ed) Spätsyndrome der Parkinson-Krankheit. Editiones Roche, Basel, pp 271–279Google Scholar
- Hornykiewicz O (1977) Biogenic amines in the central nervous system. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology vol 29, part 3. North-Holland, Amsterdam, pp 495–483Google Scholar
- Jenner P, Boyce S, Marsden CD (1986) Effect of repeated L-Dopa administration on striatal dopamine receptor function in the rat. In: Fahn S et al (eds) Recent developments in Parkinson’s disease. Raven Press, New York, pp 189–203Google Scholar
- Leenders K, Palmer A, Turton D, Quinn N, Firnau G, Garnett S, Nahmias C, Jones T, Marsden CD (1986) Dopa uptake and dopamine receptor binding visualized in the human brain in vivo. In: Fahn S etal (eds) Recent development in Parkinson’s disease. Raven Press, New York, pp 103–113Google Scholar
- Marion MH, Stocchi F, Quinn NP, Jenner P, Marsden CD (1986) Single-dose study of slow release preparation of levodopa and benseracide (Madopar HBS) in Parkinson’s disease. In: Yahr MD, Bergmann KJ (eds) Advances in neurology, vol 45. Raven Press, New York, pp 493–496Google Scholar
- Meier J, Rettig H, Hess H (1981) Biopharmazie-Theorie und Praxis der Pharmakokinetik. G Thieme, Stuttgart New York Mena MA, Muradas V, Bazan E, Reiviz J, de Yebenes JG (1986) Pharamcokinetics of L- Dopa in patients with Parkinson’s disease. In: Yahr MD, Bergmann KJ (eds) Advances in neurology, vol 45. Raven Press, New York, pp 481–486Google Scholar