Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs

-50- SUMMARY Comparative Plasma Dispositions of Ivermectin and Doramectin Following Subcutaneous and Orai Adrainistration in Dogs This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) follovving oral and subcutaneous administration (200 jjg/kg) över a 40-day period in dogs. A total of 20 cross-breed bitches, 2-5 years old and weighing 15-30 kg was used in the study. Twenty bitches were allocated by weight in to four groups (Group I, II, III and IV) of five animals each. Animals in the fırst 2 groups (Group I and II) received orally injectable solutions of IVM (Ivomec®, 1%) and DRM (Dectomax®, 1%), respectively. The other 2 groups (Group III and IV) received the same solutions subcutaneously at the same döşe rate. Heparinized blood samples (5 mi) were collected by cephalic venepuncture l day prior to drug administration and l, 2, 4, 8, 12, 16, 24, 32, 48, 72, 96 hours and 6, 9, 12, 15, 20 25, 30, 35 and 40 days post- treatment. No adverse response was observed for any of the treatments during the study. The parent molecule were detected in plasma between l h and either 25 days after oral administration of both molecules and subcutaneous administration of DRM, whereas the last detectable plasma concentration extended to 30 days following subcutaneous administration of IVM. The results indicated that IVM produced a significantly higher maximum plasma concentration (Cmax: 116.80±10.79 ng/ml) with slower absorption (tmax: 0.23±0.09 day) and larger area under the concentration vs. time curve (AUC: 236.79±41.45 ng.d/ml) as compared with DRM (Cmax: 86.47Ü9.80 ng/ml, tmax: 0.12±0.05 day, AUC: 183.48Ü3.17 ng.d/ml) follovving oral administration of both drugs; \vhereas no significant differences were observed on the pharmacokinetic parameters betvveen IVM and DRM after subcutaneous administrations. in addition, subcutaneously given IVM and DRM presented a significantly lower maximum-51- plasma concentration (IVM and DRM SC Cmax: 66.80±9.67 ng/ml and 54.78±11.99 ng/ml, respectively, IVM and DRM ÖR Cmax: 116.80±10.79 ng/ml and 86.47Ü9.80 ng/ml) with slower absorption (IVM and DRM SC tmax: 1.50±1.00 day and 1.70±0.76 day, respectively, IVM and DRM ÖR tmax: 0.23±0.09 day and 0.12±0.05 day) and larger area under the concentration vs. time curve (IVM and DRM SC AUC: 349.18±47.79 ng.d/ml and 292.10±78.76 ng.d/ml, respectively, IVM and DRM ÖR AUC: 236.79±41.45 ng.d/ml and 183.48±13.17 ng.d/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives (tı/zxz) and mean residence times (MRT) of both molecules. This study ivermectin and doramectin could be used by oral ör subcutaneous route for the control and treatment of parasitic infection in dogs.