| Ivermectin (IVM), a broad-spectrum anti-parasitic drug, is amember of theavermectins, a family of macrolidescompounds isolated fromthe fermentationproducts of Streptomycesavermitilis， and is applied as an anthelmintic andantiectoparasitic agent in livestock, fish and pets.Ivermectin is an antiparasitc medicine widely used in aquaculture. Threeexperimental groups with different IVM concentrations of7,14,21μg/L and acontrol group with2.1‰ethanol were set to study the toxic effects of IVM onDanio rerio. In the96-hours’ static acute toxicity test，indices of physiologicaland biochemical characteristics such as the activities of Lactate Dehydrogenase(LDH)，Acetylcholin esterase (AChE), Alkaline Phosphatase (ALP) in the head，and Superoxide Dismutase (SOD), Malonaldehyde(MDA), ALP in muscle weredetected. Compared with the control group, the effects of IVM on SOD activitiy inDanio rerio muscle showed the trend of inhibition at low concentration level, whilethe SOD activity increased firstly and then decreased at higher IVM concentration.During the first12hours, MDA content in fish muscle of7μg/L group wassignificantly higher than that in control group(p＜0.05), while MDA contents in fish muscle of group14μg/L and21μg/L were inhibited significantly andalthough a trend of recovery was observed, the contents were still lower than thatin control group. Overall, The effect of IVM on AChE activity has no significantdifference compared with control group in the short term, but the AChE activity inDanio rerio head of the highest concentration group（21μg/L）was significantlyinhibited after96h and the inhibition ratio was55.2%.LDH activity of headfluctuated after8h to24h, then showed a trend of recovery. The ALP activity ofhead in the14μg/L and21μg/L group were significantly inhibited after12h to24h(p＜0.05) and there was no significant difference compared with control groupin muscle（p＞0.05），which indicated that the activity of ALP in head was moresensitive than that in muscle.The effects of ivermectin on the physiological and biochemical characteristicfeatures of liver and plasma in tilapia（GIFT, Oreochromis niloticus）was studiedfollowing a single intramuscular administration. The dose of group C, D, E were0.1mg/kg,0.5mg/kg and1.0mg/kg respectively and group B was administratedwith pure ethanol and group A as the control.The result showed that MDA contentof liver in tilapia were not significantly changed except the group1.0mg/kg, and ingroup E, the MDA content was significantly increased when administrated IVMafter4h,16h and24h. In group C with the low dose, the SOD activity increasedsignificantly while the SOD activity in group D were not abviously affected.Similar affected to MDA content in group E, SOD activity in this group alsoincreased significantly at4h,16h and24h. AST and ALT activity of liver in tilapia were abviously affected by IVM, especially in group E, with the significantdecreasing of AST and ALT activity. On the contrary, the AST activity in plasmashowed difference with liver in that it increased obviously sometimes while theALT in plasma was not affected The ALP activity in liver decreased significantly inall the administed group B, C, D and E, but were not abviously affected inplama,so the changes of ALP in liver might be affected by pure ethanol and notIVM. Compared to control groups, TP contents in plasma were higher in group Cat96h,480h,600h and group E at0.5h,1.5h,4h,96h,480h,600h respectively, butno evident changing rule was observed. ALB content in plasma has the samechanging rule with TP; TG contents in liver of administed groups lowersignificantly than those in control group during the period of4h~16h and whilethose in group E were abviously affected until384h. TG contents in plasma wereaffected by IVM and the values in group D were lower than those in control groupduring the period of4h~24h.The effects of ivermectin on indexes of hemotology include parameter ofblood cell and plasma inorganic constituents in tilapia（GIFT, Oreochromisniloticus）was studied following a single intramuscular administration.The doses ofC, D and E were0.1mg/kg,0.5mg/kg and1.0mg/kg respectively, Group B wasadministrated with pure ethanol and group A was set as the control.The resultshowed that white blood cell count (WBC), blood lymphocytes count (Lymph),blood mononuclear cell (Mon), blood neutrophils count (Gran), red blood cellcount(RBC),hemoglobin content (HGB), hematocrit level (HCT), meancorpuscular volume(MCV),mean corpuscular hemoglobin(MCH), mean corpuscularhemoglobin concentration (MCHC), Red cell distribution width coefficient ofvariation (RDW) and serum magnesium ions (Mg2+), plasma calcium (Ca2+),inorganic phosphorus (P) were not obviously affected by IVM.Pharmacokinetics of ivermectin in tilapia (GIFT, Oreochromis niloticus) wascarried out following a single intramuscular administration at dose of1mg/kg. Theresults showed that after intramuscular administration, the pharmacokinetic modelof blood, muscle, kidney and spermary were best defined as two-compartmentalopen model; and the the pharmacokinetic mode of liver were best defined asone-compartmental open model.The pharmacokinetics equation in blood, muscle,kidney, spermary and liver were as following respectively:Blood: C（t-0.22）4（t-0.22）1=0.215e-0.016＋0.198e0－0.413e-1.29；Muscle: C2=4.219e-0.037t＋0.217e-0.004t－4.436e-0.049t；Kidney:C-0.005t-0.031t3=0.001e＋0.713e-0.004t－0.714e；Spermary: C-0.119t4=3.479e-0.096t＋0.25e-0.003t－3.729e；Liver:C0.004t5=1.764（e-－e-0.132t）After intramuscular administration, non-compartmental pharmacokineticsparameters in blood, muscle, kidney, spermary and liver were as followingrespectively. Cmaxwere0.424mg/L,0.757mg/kg,0.618mg/kg,0.571mg/kg,1.514mg/kg respectively, And Tmaxwere8h,24h,8h,16h and24h respectively.AUC were506.1mg/(L h),89.4mg/(L h),143.8mg/(L h),99.8mg/(L h) and508mg/(L h) respectively. MRT were1811h,177h,195h,312h and260h respectively. t1/2were1208h,155h,67h,231h and166h respectively. ThePharmacokinetic characteristics of IVM in tilapia (GIFT, Oreochromis niloticus)could be explaned as fast absorption, wide distribution and slow elimination.Whenwater temperature was （26±1）℃, drug withdrawal times in muscle was25dfollowing a single intramuscular administration at dose of1mg/kg. |
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