Elimination kinetics of synthetic interferon inducer tilorone in experimental animals

Abstract

Żuk M, Sumriy SK, Zhuk OV. Elimination kinetics of synthetic interferon inducer tilorone in experimental animals. J Pre-Clin Clin Res. 2017; 11(2) 3 H]-I in rats and mice was studied following a single oral and intravenous administration. The excretion mass balance was monitored in the faeces and urine of rats and mice for 5 and 10 days, respectively. Radioactivity was determined in the samples of excreta using a liquid scintillation counter. Results. In rats, [3 H]-I were nearly fully (~80%) eliminated with excreta in 5 days, indicating a lack of any significant accumulation of the drug in the body. Faecal excretion of tilorone predominated (69.0% ± 2.8%), while the elimination in urine was less significant (9.8%8 ± 1.2%). A different pattern of elimination kinetics was observed in mice as excretion proceeded with equal efficiency in urine (27.85-28.9%) and faeces (26.45-24.4 %), regardless of the route of administration of the substance and at a substantially slower rate compared to rats: only 57.35-52.68% of total radioactivity was eliminated over 10 days following oral and intravenous administration of tilorone, respectively. MRT of tilorone in rats was 36 h and in mice 120-150 h. Conclusion. Parameters for the excretion of tilorone showed significant differences between the 2 groups of animals. Using the example of tilorone excretion kinetics validates the presented novel modified approach to determine the mean residence time (MRT) and amount of drug eliminated from the body during an infinitely long experimental period. This approach can be generally applied for interpretation of nonlinear elimination kinetics of xenobiotics.