Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers.

Objective: Thymosin α1, an immunomodulatory endogenous peptide, has been shown to be effective in the treatment of chronic hepatitis B and C. In this study, single-and 5-day multiple-dose pharmacokinetics were characterized in nine Caucasian volunteers after subcutaneous administration of 900 μg/m 2 thymosin α1. Methods: Using a randomized, 3-way crossover design three available drug formulations were compared: Zadaxin (SciClone), Timosina (Sclavo), and Thymosin α1 (Tα1-HLR; Hoffmann La Roche). AUC, C max , t max , t 1/2 , Cl/f, and the volume of distribution, V Z /f, were derived by model-independent methods. Results: Endogenous serum concentrations were below the limit of quantification (0.10 μg/l) of the enzyme-linked immunosorbent assay method in most subjects. Thymosin α1 was well absorbed with a mean t max between 1 - 2 hours from all galenic formulations. C max concentrations of 30 to 80 μg/l and AUC 0- ∞ from 95 to 267 μg x h/l did not differ between single-and multiple-dose administration of all drugs. This apparent lack of accumulation was supported by the short elimination half-life of less than 3 hours. As indicated by a V Z /f in the range of 30 - 40 1, thymosin at appears to distribute within the extracellular volume. AUC and C max were similar for Zadaxin and Tα1-HLR, but higher after administration of Timosina. Conclusion: Thymosin α1 kinetics from this study are comparable to those previously obtained in Japanese volunteers or cancer patients, but may be influenced by the drug formulation used.