TY - JOUR
T1 - Anorectic efficacy and safety of the diethylpropion-topiramate combination in rats
AU - Cortés-Moreno, Gabriela Y.
AU - Roa-Coria, José E.
AU - Zúñiga-Romero, Ángel
AU - Huerta-Cruz, Juan C.
AU - Lara-Padilla, Eleazar
AU - del Valle-Laisequilla, Cecilia F.
AU - Rocha-González, Héctor I.
AU - Reyes-García, Juan G.
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/8
Y1 - 2018/8
N2 - (Table presented.). 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.
AB - (Table presented.). 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.
KW - anorectic
KW - blood pressure
KW - diethylpropion
KW - isobologram
KW - obesity
KW - topiramate
UR - http://www.scopus.com/inward/record.url?scp=85052846493&partnerID=8YFLogxK
U2 - 10.1002/ddr.21434
DO - 10.1002/ddr.21434
M3 - Artículo
C2 - 30188585
SN - 0272-4391
VL - 79
SP - 225
EP - 233
JO - Drug Development Research
JF - Drug Development Research
IS - 5
ER -