Preclinical Pharmacokinetic and Toxicity Studies of Anthrafuran – A New Antitumor Agent

Portnoi, Yu. A.; Довженко, С. А.; Kobrin, Mikhail B; Переверзева, Э. Р.; Трещалин, М. И.; Голибродо, В. А.; Shchekotikhin, Andrey E.; Firsov, Alexander A.

doi:10.1007/s11094-020-02164-4

Cited by 2 publications

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“…Some differences in the results of the investigations, apparently, are associated with the fact that chronic toxicity in rats was examined using the drug substance, and in the study on rabbits, a drug formulation was used. In previous pharmacokinetic researches, it was found that after oral administration of the drug formulation, AF was absorbed faster, and its maximum concentration in the blood was higher than after the administration of a substance [ 9 ]. AF substance is absorbed 2 times slower from the gastrointestinal tract into the blood; therefore, its damaging effect on the gastric and intestinal mucosa of rats is more prolonged and is manifested to a greater extent than in rabbits.…”

Section: Discussionmentioning

confidence: 99%

“…A study of the kinetics of dissolution of anthrafuran substance in bio-relevant media (for example, in artificial gastric juice at 37 °C) showed that anthrafuran refers to preparations with a low biopharmaceutical solubility (look for Biopharmaceutics Classification System, BCS) [ 8 ]. To increase biopharmaceutical solubility, an oral dosage form based on anthrafuran and liquid pharmaceutically acceptable carriers with a high release rate of the active ingredient are obtained [ 9 ]. Most anticancer drugs are applied parenterally, as this route of administration provides fast and maximal bioavailability of the agents and therefore, accurate dosing during the whole course of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

et al. 2021

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A new antitumor multi-target drug anthrafuran, with cellular targets such as topoisomerase I/II and some protein kinases, was obtained in Gause Institute of New Antibiotics and was demonstrated to have a reliable specific effect on different murine and human tumor models by oral administration. In this study, we focused on the evaluation of subchronic toxicity of oral anthrafuran drug formulation (AF) on Chinchilla rabbits. The absence of any changes in the condition or behavior of animals was shown for oral anthrafuran. Changes with reversible and dose-dependent hepato- and nephrotoxicity at low doses, as well as hemato- and gastrointestinal toxicity at high doses, were confirmed pathomorphologically. The identified toxic properties are extremely valuable, since oral anthrafuran does not have the limiting cardio- and myelotoxicity. Anthrafuran with 2 mg/kg/day or 6 mg/kg/day doses was administrated orally over 15 days. Investigations include assessment of the body weight, hematological and serum biochemical parameters and urinalysis, electrocardiography and pathomorphological evaluation of the internal organs. Quantitative data were processed statistically with Student’s t-Test, p < 0.05. Revealed during the subchronic study were the favorable toxicological properties of oral anthrafuran as opposed to clinical anthracyclines, oral idarubicin, or parenteral doxorubicin, which allows it to be considered promising for further research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

et al. 2021

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Experimental Evaluation of Anticancer Efficiency and Acute Toxicity of Anthrafuran for Oral Administration

et al. 2020

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The new antitumor agent anthrafuran has demonstrated a consistent effect in murine tumor models when administered parenterally due to the simultaneous inhibition of multiple cellular targets such as topoisomerases I/II and protein kinases. In this study, we assessed the anticancer efficiency and acute toxicity of anthrafuran administered orally. The action of anthrafuran was studied on transplanted tumor models which included P388 leukemia, Ca755 mammary adenocarcinoma, LLC lung carcinoma, and T47D human breast cancer xenografts on Balb/c nude mice. A significant antitumor efficacy of oral anthrafuran was revealed for all tested tumor models as follows: T/Cmax = 219% for P388, TGImax = 91% for Ca755, TGImax = 84% with CRmax = 54% for LLC, and T/C = 38% for T47D. The optimal treatment schedule of orally administered anthrafuran was 70–100 mg/kg given daily for five days. The LD50 value of orally administered anthrafuran (306.7 mg/kg) in mice was six times higher than that for i.p. administration (52.5 mg/kg). The rates of antitumor efficacy and acute toxicity indicate the high potential for further research on anthrafuran as a new original oral anticancer multitarget agent with an expected satisfactory tolerability and bioavailability.

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Preclinical Pharmacokinetic and Toxicity Studies of Anthrafuran – A New Antitumor Agent

Cited by 2 publications

References 4 publications

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

Experimental Evaluation of Anticancer Efficiency and Acute Toxicity of Anthrafuran for Oral Administration

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