Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy subjects

Eur J Pharm Biopharm. 1998 Sep;46(2):223-8. doi: 10.1016/s0939-6411(98)00022-8.

Abstract

A multiple-dose study was performed to assess the pharmacokinetic profile of a new levodopa/benserazide dual-release formulation (DRF) in comparison with a conventional slow-release formulation (SRF). The study was of an open label, randomized, two-way cross-over design and was conducted in 18 subjects. Assessment of the two formulations was at day 1 (single-dose) and at day 7 after a 5-day t. i.d. pre-treatment (100 mg levodopa and 25 mg benserazide) in fasting state. The pharmacokinetic parameters reflecting bioavailability, accumulation and metabolism of levodopa were determined. The levodopa pharmacokinetics of the new DRF showed rapid absorption (tmax=1.1 h), followed by sustained levodopa plasma concentrations, similar to the SRF. Following multi-dose administration, the peak plasma concentration of the new DRF was 90% higher compared to the SFR (Cmax=2.1 and 1.1 microg/ml, respectively). The bioavailability was significantly increased by 40% (AUC0-infinity=6.1 and 4.3 microg x h/ml, respectively). The new DFR was well tolerated as shown by the low incidence of mild side effects. In conclusion, the results of this study confirmed the levodopa dual-release properties of this new levodopa/benserazide formulation.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Benserazide / administration & dosage
  • Benserazide / blood
  • Benserazide / pharmacokinetics*
  • Biological Availability
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Drug Combinations
  • Fasting
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / blood
  • Levodopa / pharmacokinetics*
  • Metabolic Clearance Rate
  • Time Factors
  • Tyrosine / analogs & derivatives*
  • Tyrosine / blood
  • Tyrosine / pharmacokinetics

Substances

  • Delayed-Action Preparations
  • Drug Combinations
  • Tyrosine
  • Levodopa
  • Benserazide
  • 3-methoxytyrosine