Abstract
Opioid receptor antagonists are widely used for the treatment of alcohol dependence. Currently, original drug Odelepran (INN: ondelopran) with a unique binding profi le to all three types of human opioid receptors (μ, κ, δ) is being developed by R-Pharm.Aim of the study. To investigate a cancerogenic poten al of the new opioid receptor antagonist ondelopran in a twoyear study in rats Materials and methods. The study cancerogenic potencial was performed in male and female Wistar rats at the age of 8–10 weeks at the start of experiment. All animals were allocated to 8 groups. Each group consisted of 50 animals of each sex. Test item (ondelopran fi lm-coated tablets, 125 mg), was administered to the animals intragastrically as a tablets suspension in 1% starch solution daily, 5 days a week for 24 months in two doses: 10 mg/kg (equivalent therapeutic dose for humans) and 100 mg/kg. Animals of control groups were administered with placebo and vehicle (1% starch solution). Clinical observation and examination of animals were conducted weekly to detect any signs of intoxication; dynamics of the body weight and registration of animal deaths were also assessed. To assess the rate of the pathological changes, the macro- and microscopic examina on of inner organs and neoplasms was conducted.Results. During the study the mortality rates did not diff er between the groups. Clinical signs ts.and symptoms of intoxication upon administration of the tested item and placebo were not observed. Neoplasms were found in the organs of all groups of animals. More than 30 variants of neoplasms were identifi ed upon pathomorphological examination. The identifi ed tumors are typical for rats and considered as spontaneous age-related pathology. There was no statistically signifi cant diff erences between groups in the total incidence of tumors.Conclusion. To conclude the above said, the test item of the ondelopran fi lm-coated tablets, 125 mg have no carcinogenic properties.
Highlights
Data and Variations in Tumor Rates of Control Rats and Mice
Opioid receptor antagonists are widely used for the treatment of alcohol dependence
To investigate a cancerogenic potential of the new opioid receptor antagonist ondelopran in a twoyear study in rats Materials and methods
Summary
Оценка канцерогенного потенциала нового опиоидного антагониста онделопрана при введении крысам в течение двух лет. Исследование канцерогенного потенциала проводили на половозрелых самцах и самках крыс породы Wistar, в возрасте 8–10 нед к началу эксперимента. Исследуемый препарат (онделопрана таблетки, покрытые пленочной оболочкой, 125 мг) вводили животным внутрижелудочно в виде суспензии таблеточной массы в 1% растворе крахмала ежедневно, 5 дней в неделю на протяжении 24 мес в двух дозах — 10 мг/кг (эквивалентная терапевтическая доза для человека) и 100 мг/кг. Животным контрольных групп вводили плацебо (вспомогательные компоненты таблетки) и 1% раствор крахмала в качестве носителя. С целью регистрации частоты развития патологических изменений проводили макро- и микроскопическое исследование внутренних органов и новообразований. При сравнении частоты возникновения опухолей статистически значимых межгрупповых различий не выявлено. Ключевые слова: алкогольная зависимость, антагонисты опиатных рецепторов, онделопран, канцерогенность, частота возникновения опухолей, крысы. R-Pharm JSC, 111B Leninsky ave., Moscow 119421, Russian Federation
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