Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats

• Published in: Drug development research 2018-08, Vol.79 (5), p.225-233
• Main Authors: Cortés‐Moreno, Gabriela Y., Roa‐Coria, José E., Zúñiga‐Romero, Ángel, Huerta‐Cruz, Juan C., Lara‐Padilla, Eleazar, del Valle‐Laisequilla, Cecilia F., Rocha‐González, Héctor I., Reyes‐García, Juan G.
• Format: Article
• Language: English
• Subjects: Animals; anorectic; Appetite Depressants - administration & dosage; Appetite Depressants - adverse effects; Blood pressure; Blood Pressure - drug effects; Clinical trials; Confidence intervals; Dietary restrictions; diethylpropion; Diethylpropion - administration & dosage; Diethylpropion - adverse effects; Dose-Response Relationship, Drug; Drug dosages; Drug Synergism; Drugs; Effectiveness; Humans; isobologram; Male; Medical research; Milk; obesity; Rats; Rats, Wistar; Safety; Topiramate; Topiramate - administration & dosage; Topiramate - adverse effects
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21434

Preclinical Research & Development Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose‐dependent fashion in either nondeprived or 12 hr food‐deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.