Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data
| Autor: | Kerstin Breithaupt-Grögler, Henning Blume, Georg Niebch, Katharina Erb, Gustav G Belz, Barbara Schug, Robert Hermann, Edith Schneider |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Chromatography Cross-Over Studies Thioctic Acid Dose-Response Relationship Drug Chemistry Cmax Pharmaceutical Science Half-life Stereoisomerism Free Radical Scavengers Pharmacology Crossover study Dose–response relationship Pharmacokinetics Oral administration Area Under Curve Humans Regression Analysis Enantiomer Chromatography High Pressure Liquid Half-Life |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 8(1) |
| ISSN: | 0928-0987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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