J. Pharm. Pharmacogn. Res., vol. 13, no. 4, pp. 1288-1298, Jul-Aug 2025.

DOI: https://doi.org/10.56499/jppres24.2038_13.4.1288

Original Article

Influence of iodine-containing complex on the toxicity of drugs used for the treatment of acute respiratory viral diseases and influenza virus in combined application

[Influencia del complejo que contiene yodo en la toxicidad de los medicamentos utilizados para el tratamiento de enfermedades virales respiratorias agudas y del virus de la influenza en aplicación combinada]

Lyudmila Ivanova*, Ilya Korotetskiy, Bahkytzhan Kerimzhanova, Sergey Shilov, Natalya Zubenko, Tatyana Kuznetsova, Raikhan Parenova, Alexandr Ilin

JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan.

*E-mail: lyudmila_69.69@mail.ru, l.ivanova@scaid.kz

Abstract

Context: One approach to assessing pharmacodynamic drug interactions is the practical application of the Chou-Talalay theory and its combination index theorem. The algorithm for studying and analysing the effects of combinations, according to Chou-Talalay, allows for the calculation of the direction and strength of pharmacodynamic interactions using the combination index (CI) values and to establish the dose reduction index (DRI) for each component of the combination. The algorithm allows for the analysis of combinations of different qualitative and quantitative compositions and calculates the result of interaction at any level of toxicological effect in laboratories engaged in drug development and research.

Aims: To evaluate the effect of FS-1 on the toxicity of rimantadine, oseltamivir, and acetylsalicylic acid (ASA) in combined in vitro experiments.

Methods: The combined cytotoxicity effect of drugs was evaluated using neutral red on MDCK cells. The type of drug interaction was determined using the principle of median-effect and CI by correlation of doses and effects, the ratio of the value of programmed cell death to the value of actual cell death using the Chou-Talalay method.

Results: It was found that the combination FS-1/rimantadine, FS-1/oseltamivir, and FS-1/ASA can significantly reduce their toxic properties. The CI of the combined use of FS-1/rimantadine was CI = 2.018; FS-1/oseltamivir CI = 13.726, and FS-1/ASA CI = 1.518.

Conclusions: The use of Chou-Talalay algorithm makes it possible to develop recommendations for the rational use and dosing of drug combinations in clinical practice, as well as to assess the prospects for the development of new combined therapeutic technologies.

Keywords: algorithm, drug toxicity; antagonism; Chou-Talalay modeling method; combined use; combination index.

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Resumen

Contexto: Un enfoque para evaluar las interacciones farmacodinámicas de los fármacos es la aplicación práctica de la teoría de Chou-Talalay y su teorema del índice de combinación. El algoritmo para estudiar y analizar los efectos de las combinaciones según Chou-Talalay permite calcular la dirección y la intensidad de las interacciones farmacodinámicas mediante los valores del índice de combinación (IC) y establecer el índice de reducción de dosis (IRD) para cada componente de la combinación. El algoritmo permite analizar combinaciones de diferentes composiciones cualitativas y cuantitativas y calcula el resultado de la interacción a cualquier nivel de efecto toxicológico en laboratorios dedicados al desarrollo e investigación de fármacos.

Objetivos: Evaluar el efecto de FS-1 sobre la toxicidad de rimantadina, oseltamivir y ácido acetilsalicílico (AAS) en experimentos in vitro combinados.

Métodos: Se evaluó el efecto citotóxico combinado de los fármacos utilizando rojo neutro en células MDCK. El tipo de interacción farmacológica se determinó mediante el principio de mediana-efecto y el IC mediante la correlación de dosis y efectos, la razón entre el valor de la muerte celular programada y el valor de la muerte celular real mediante el método de Chou-Talalay.

Resultados: Se observó que la combinación de FS-1/rimantadina, FS-1/oseltamivir y FS-1/AAS puede reducir significativamente sus propiedades tóxicas. El IC del uso combinado de FS-1/rimantadina fue de 2,018; el de FS-1/oseltamivir fue de 13,726 y el de FS-1/AAS fue de 1,518.

Conclusiones: El uso del algoritmo de Chou-Talalay permite desarrollar recomendaciones para el uso racional y la dosificación de combinaciones de fármacos en la práctica clínica, así como evaluar las perspectivas de desarrollo de nuevas tecnologías terapéuticas combinadas.

Palabras Clave: algoritmo, toxicidad farmacológica; antagonismo; método de modelado de Chou-Talalay; uso combinado; índice de combinación.

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Citation Format: Ivanova L, Korotetskiy I, Kerimzhanova B, Shilov S, Zubenko N, Kuznetsova T, Parenova R, Ilin A (2025) Influence of iodine-containing complex on the toxicity of drugs used for the treatment of acute respiratory viral diseases and influenza virus in combined application. J Pharm Pharmacogn Res 13(4): 1288–1298. https://doi.org/10.56499/jppres24.2038_13.4.1288
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