Evaluation of pharmacokinetics and efficacy of ivermectin following oral administration in dogs against experimental infection of Ctenocephalides felis felis and Rhipicephalus sanguineus

Abstract

With the increasing number of pets in home the human-animal relationship is increasingly close and care about control disease growing. Ivermectin (IVM) is frequently used because its proven safety. IVM is recommended for the treatment of demodectic scabies and prevention of heartworm in dogs, but informally is extremely used to control of Ctenocephalides felis felis and Rhipicephalus sanguineus. The aim of this study is evaluate the use of IVM in dogs, by the oral route at 0.6μg/kg dose, against experimental infection of these parasites using the construction of the plasma concentration curve and efficacy study. A IVM quantification method in canine plasma using HPLC-FL was developed and validated based on RE n°899/03 ANVISA. The samples collected during the efficacy test was analyzed by this validated method and prove C of 350ng/mL at 4h (t) and AUC of 8411ng/h/mL. Spite of formulation have shown good absorption, the highest efficiency values found for Rhipcephalus sanguineus and Ctenocephalides felis felis were very low, 35% and 67% respectively, demonstrating this not be the most appropriate treatment for the control of these parasites.

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

“…ng/ml and 137 ng/ml, respectively. When AUC and C max values were normalized to same dose, our parameters were similar to previously reported values in Beagle dogs at different doses (0.069-0.3 mg/ kg) (Al-Azzam, Fleckenstein, Cheng, Dzimianski, & McCall, 2007;Dunn et al, 2011;Walther, Allan, & Roepke, 2015), but lower than in cross-bred dogs at 0.2 mg/kg dose (Gokbulut, Karademir, Boyacioglu, & McKellar, 2006) and in Beagle dogs at 0.6 mg/kg dose (Magalhães et al, 2016) after oral administration. Significant differences of the AUC in these studies may be related to the affinity to fatty tissues due to high lipophilicity of ivermectin, P-pg transport F I G U R E 1 Comparative mean (± SD) plasma concentration profiles for ivermectin (IVM) obtained after its administration (0.4 mg/kg) either alone or co-administered with praziquantel (PZQ, 10 mg/kg) both given by the oral route to dogs (n = 6) TA B L E 1 Plasma pharmacokinetic parameters obtained after the oral administration of ivermectin (0.4 mg/kg) to dogs either alone or co-administered with praziquantel (10 mg/kg) (mean ± SD, n = 6) b…”

“…ng/ml and 137 ng/ml, respectively. When AUC and C max values were normalized to same dose, our parameters were similar to previously reported values in Beagle dogs at different doses (0.069–0.3 mg/kg) (Al‐Azzam, Fleckenstein, Cheng, Dzimianski, & McCall, ; Dunn et al., ; Walther, Allan, & Roepke, ), but lower than in cross‐bred dogs at 0.2 mg/kg dose (Gokbulut, Karademir, Boyacioglu, & McKellar, ) and in Beagle dogs at 0.6 mg/kg dose (Magalhães et al., ) after oral administration. Significant differences of the AUC in these studies may be related to the affinity to fatty tissues due to high lipophilicity of ivermectin, P‐pg transport activity, and entering the enterohepatic circulation (Canga et al., ; Hennessy & Alvinerie, ).…”

“…Mealey and Meurs (2008) have reported a relatively high percentage of mixed-breed dogs with the ABCB1 mut/ mut (7/238 [3%]) or ABCB1 mut/wt (19/238 [8%]) genotype. The T max and t 1/2λz (14.0 and 110 hr, respectively) were determined considerably longer in our study than previously reported values in dogs for ivermectin (Al-Azzam et al, 2007;Dunn et al, 2011;Gokbulut et al, 2006;Magalhães et al, 2016;Walther et al, 2015). This can be explained by the formulation of ivermectin.…”

“…Plasma pharmacokinetics of ivermectin (Gokbulut, Karademir, & Boyacioglu, ; Gokbulut et al., ; Lanusse et al., ; Magalhães et al., ; Mestorino, Turic, Pesoa, Echeverría, & Errecalde, ) and praziquantel (Giorgi et al., ; Hong et al., ; Qian, Wei, Hao, & Tang, ; Sun & Bu, ) have been determined for different administration routes in some species. Although there are several commercial products combining the two drugs together for dogs, no data on the combination pharmacokinetics of ivermectin and praziquantel in dogs following oral administration were reported.…”

“…Plasma pharmacokinetics of ivermectin (Gokbulut, Karademir, & Boyacioglu, 2007;Gokbulut et al, 2010;Lanusse et al, 1997;Magalhães et al, 2016;Mestorino, Turic, Pesoa, Echeverría, & Errecalde, 2003) and praziquantel (Giorgi et al, 2003;Hong et al, 2003;Qian, Wei, Hao, & Tang, 2017;Sun & Bu, 2012) have been determined for different administration routes in some species.…”