Transl Clin Pharmacol.  2016 Sep;24(3):137-142. 10.12793/tcp.2016.24.3.137.

Comparison of R(+)-α-lipoic acid exposure after R(+)-α-lipoic acid 200 mg and 300 mg and thioctic acid 600 mg in healthy Korean male subjects

• Yoon J
• Moon SJ
• Lee KO
• Yoon SH
• Jang IJ
• Yu KS
• Lee S

• KMID: 2351800
• DOI: http://doi.org/10.12793/tcp.2016.24.3.137

Abstract

Alpha-lipoic acid, a physiological form of thioctic acid, is a strong antioxidant that relieves diabetic neuropathic symptoms. R(+)-α-lipoic acid shows superior antioxidative effects to its racemate. We compared the pharmacokinetics (PKs) and tolerability of R(+)- and S(-)-α-lipoic acid after a single oral dose of R(+)-α-lipoic acid, Dexid®, and its racemate, thioctic acid in healthy male subjects. We used an open-label, randomized, single-dose, three-treatment, parallel study design to compare the PK exposure of the active form, R(+)-α-lipoic acid. Thirty subjects completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean±SD) of R(+)-α-lipoic acid after doses of R(+)-α-lipoic acid 200 mg, 300 mg and thioctic acid 600 mg were 4186.8±1956.7, 6985.6±3775.8 and 6498.4±3575.6 µg/L, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC(last)) were 1893.6±759.4, 3575.2±1149.2 and 3790.0±1623.0 µg·h⁻¹·L⁻¹, respectively. The geometric mean ratio and 90% confidence intervals of R(+)-α-lipoic acid 200 mg to thioctic acid 600 mg for the C(max) and AUC(last) were 0.71 (0.43-1.15) and 0.51 (0.37-0.70), respectively. The corresponding R(+)-α-lipoic acid 300 mg to thioctic acid 600 mg values were 1.11 (0.68-1.80) and 0.97 (0.71-1.34), respectively. In conclusion, R(+)-α-lipoic acid 300 mg showed PK characteristics similar to those of thioctic acid 600 mg and both formulations were well tolerated.

Keyword

pharmacokinetics; racemate; R(+)-α-lipoic acid; thioctic acid; tolerability

MeSH Terms

Humans
Male*
Pharmacokinetics
Plasma
Thioctic Acid*
Thioctic Acid

Figure

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  Figure 1. Disposition of the study subjects.

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  Figure 2. Mean plasma concentration-time profiles of R(+)-α-lipoic acid after a single oral administration of R(+)-α-lipoic acid 200 mg or 300 mg or thioctic acid 600 mg. Inset shows profile by log-linear scale. Bars represent SD. (∗ N=2 for R(+)-α-lipoic acid 200 mg, N=7 for R(+)-α-lipoic acid 300 mg and thioctic acid 600 mg)

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  Figure 3. Comparison of peak concentration (Cmax, upper) and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast, lower) of R(+)-α-lipoic acid after a single oral administration of R(+)-α-lipoic acid 200 mg or 300 mg or thioctic acid 600 mg. Boxes indicate interquartile range and whisker bars indicate 10th and 90th percentiles. Horizontal bars locate in the middle of the boxes represent median and the long-dashed line shows mean.

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