Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa

Int J Pharm. 2008 Nov 19;364(1):54-63. doi: 10.1016/j.ijpharm.2008.08.016. Epub 2008 Aug 22.

Abstract

In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers. Two concepts of sustained-release floating minitablets--Levo-Form 1 (matrix) and 2 (coated)--were evaluated and compared to the marketed product Prolopa HBS 125. All the floating forms were radiolabelled with (111)In in order to evaluate their gastric residence time using gamma-scintigraphy. It was shown that the three formulations offered almost the same mean gastric residence time, which was about 240 min. Prolopa HBS 125 and Levo-Form 2 presented intragastric disintegration, which can lead to a more pronounced "peak & valley" effect on the plasma concentration-time profile of levodopa. In contrast, the plasma concentration-time profile of levodopa following the administration of Levo-Form 1 was more evenly distributed. Moreover, Levo-Form 1 provided the lowest variations between men and women in terms of AUC and C(max) values. Finally, when the same amount of inhibitors of extracerebral dopa decarboxylase--carbidopa and benserazide--had been administrated, the mean AUC, C(max) and T(max) values obtained for benserazide were lower than those obtained for carbidopa.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacokinetics*
  • Area Under Curve
  • Carbidopa / administration & dosage*
  • Carbidopa / adverse effects
  • Carbidopa / pharmacokinetics*
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Drug Combinations
  • Female
  • Half-Life
  • Humans
  • Indium Radioisotopes
  • Isotope Labeling
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Levodopa / pharmacokinetics*
  • Male
  • Powders
  • Radionuclide Imaging
  • Tablets
  • Tissue Distribution
  • Young Adult

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Drug Combinations
  • Indium Radioisotopes
  • Powders
  • Tablets
  • Levodopa
  • Carbidopa