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

Abstract

OBJECTIVE:

Thymosin alpha1, 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 microg/m2 thymosin alpha1.

METHODS:

Using a randomized, 3-way crossover design three available drug formulations were compared: Zadaxin (SciClone), Timosina (Sclavo), and Thymosin alpha1 (Tal-HLR; Hoffmann La Roche). AUC, Cmax, 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 microg/l) of the enzyme-linked immunosorbent assay method in most subjects. Thymosin alpha1 was well absorbed with a mean t(max) between 1-2 hours from all galenic formulations. Cmax concentrations of 30 to 80 microg/l and AUC(0-infinity) from 95 to 267 microg 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 l, thymosin alpha1 appears to distribute within the extracellular volume. AUC and Cmax were similar for Zadaxin and T alpha1-HLR, but higher after administration of Timosina.

CONCLUSION:

Thymosin alpha1 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.

• Authors: K L Rost, W Wierich, F Masayuki, C W Tuthill, D L Horwitz, W M Herrmann
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 37 Issue 1 Pg. 51-7 (Jan 1999) ISSN: 0946-1965 [Print] Germany
• PMID: 10027483 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Adjuvants, Immunologic
• Thymosin

Topics

• Adjuvants, Immunologic (blood, pharmacokinetics)
• Administration, Cutaneous
• Adult
• Cross-Over Studies
• Enzyme-Linked Immunosorbent Assay
• Half-Life
• Humans
• Male
• Thymosin (adverse effects, blood, pharmacokinetics)
• Time Factors