Abstract
SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13–19 μM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.
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Acknowledgements
The authors’ work reported herein was supported by Fundamental Research Grant Scheme (FRGS) (04-01-015-1674 FR) which was awarded by the Malaysia Ministry of Higher Education (MOHE) and a grant (BMRC/09/1/21/19/595) from the BioMedical Research Council of Singapore.
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F.W.S.W., J.C.W.L. and J.S. conceived and designed research. J.C.W.L. and S.R.S. conducted experiments. J.C.W.L., A.C.H.Y., F.W.S.W. and J.S. contributed new reagents or analytical tools. S.M.S., F.W.S.W., J.C.W.L. and J.S. analysed data. J.C.W.L. wrote the manuscript. All authors read and approved the manuscript. All data were generated in-house and that no paper mill was used in the main manuscript.
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S.M. Sidik Deceased 18 March 2019.
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Lim, J.C.W., Sagineedu, S.R., Yong, A.C.H. et al. Toxicological and pharmacokinetic analysis at therapeutic dose of SRS27, an investigational anti-asthma agent. Naunyn-Schmiedeberg's Arch Pharmacol 394, 95–105 (2021). https://doi.org/10.1007/s00210-020-01966-3
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DOI: https://doi.org/10.1007/s00210-020-01966-3