Intraperitoneal Administration as an Alternative to Intravenous for Classical Antitumor Cytostatics at the Preclinical Stage of Study

Background. Intraperitoneal administration of drugs is a common practice in preclinical studies using laboratory animals. The distinctive features of the intraperitoneal route of administration are ease to master, simplicity of execution, as well as the possibility of repeated use. According to the parameters of pharmacokinetics and the rate of onset of effect, this route is comparable to the intravenous route, which is mandatory in the preclinical study of drugs intended for systemic application, but is more time-consuming and limited in long-term experiments. The aim of the study. Evaluation of the possibility of using intraperitoneal administration as an alternative to intravenous in preclinical studies using the acute toxicity and antitumor efficacy of classical cytostatics as an example. Materials and methods. To confirm the use of the intraperitoneal route of administration as an alternative to intravenous, comparative experiments on the acute toxicity and antitumor efficacy of these two routes in female BDF1 mice were carried out. Contemporary anticancer drugs from different classes — doxorubicin, cyclophosphamide, and 5-fluorouracil — were used in the experiment. Litchfield and Wilcoxon method was used to assess acute toxicity. The antitumor efficacy was compared on a model of intraperitoneal transferable P388 murine lymphocytic leukemia using the treatment/control study. Results. The calculated toxic doses in the experiment to determine the acute toxicity of doxorubicin with intravenous and intraperitoneal routes of administration did not differ significantly. The parameters of acute toxicity of alkylating agents and antimetabolites, judging by the data obtained during their determination for cyclophosphamide and 5-fluorouracil, depend on the route of administration of the compounds. In the experimental determination of antitumor efficacy, intravenous and intraperitoneal routes of administration proved to be equally effective for each representative of the classes used. Conclusion. The obtained results demonstrated that the intraperitoneal method of administration is a justified alternative to the intravenous method in the experimental determination of the antineoplastic activity of alkylating agents, antitumor antibiotics, and antimetabolites. For antitumor antibiotics, the application of an intraperitoneal route of administration in determining acute toxicity is also a possible substitute for intravenous administration. The intraperitoneal route may be an alternative to the intravenous route for alkylating drugs and antimetabolites at the initial stages of pharmacological studies, but it is necessary to take into account the peculiarities of their pharmacokinetics.

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