Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data

Eur J Pharm Sci. 1999 Apr;8(1):57-65. doi: 10.1016/s0928-0987(98)00061-x.


Thioctic acid (TA), a racemate of R-(+)- and S-(-)-enantiomers of alpha-lipoic acid, acts as a powerful lipophilic, free-radical scavenger and is used in the treatment of diabetic neuropathy. This trial investigated the dose-linearity of enantiomer pharmacokinetics following the oral administration of single doses of 50 to 600 mg TA (formulation provided by ASTA (Medica)) in healthy volunteers. TA enantiomer concentrations in individual and pooled plasma samples were determined using enantioselective, high-performance liquid chromatography. TA was rapidly absorbed (tmax, 0.5 to 1 h). Maximum plasma concentrations (Cmax) of the R-(+)-enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg: 135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA, 978.20 ng/ml S-(-)-TA; geometric means). The decline observed in the plasma concentration was steep (t1/2, 0.5 h). The dose-linearity and proportionality of pharmacokinetic parameters could be demonstrated on an intra-individual basis and for the group geometric means. An analysis of pooled plasma samples proved to be a suitable means for deriving reliable first-sight results prior to individual assessments.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Free Radical Scavengers / administration & dosage*
  • Free Radical Scavengers / adverse effects
  • Free Radical Scavengers / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Regression Analysis
  • Stereoisomerism
  • Thioctic Acid / administration & dosage*
  • Thioctic Acid / adverse effects
  • Thioctic Acid / pharmacokinetics*


  • Free Radical Scavengers
  • Thioctic Acid