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Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats
Journal article   Open access   Peer reviewed

Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats

Xiaodan Yang, Junjie Li, Shu Chen, Liyin Xiao, Dongmin Cao, Xiaolian Wu, Hejie Li, Guoying Ni, Tianfang Wang, Guoqiang Chen, …
Evidence-Based Complementary and Alternative Medicine, Vol.2022, pp.1-13
2022
PMCID: PMC9363195
PMID: 35958922
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Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats4.15 MBDownloadView
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https://doi.org/10.1155/2022/9869293View
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Abstract

Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the eecacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. is paper investigated the pharmaceutical kinetic proole, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. e results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (C max) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T 1/2 was 4.58 hr, and AUC 0-last was 1890 h × ng/mL. In female rats, C max was 256 ng/mL, with an average drug retention time of 2.96 hr, T 1/2 of 1.33 hr, and AUC 0-last of 740 h × ng/mL. e results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T 1/2 extended, and C max , AUC 0-last , and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. e results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.

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