Pharmacokinetics Of Compound Ivermectin Injection In Pigs

In this research,preparing compound ivermectin injection,determining the content of principal agents in compound ivermectin injection and studying its stability were all performed.The research has established the method of detection ivermectin(IVM) and albendazole sulphoxide hydrochloride(ABZSO) after extraction from plasma of pigs, using reversed-phase high performance liquid chromatography(RP-HPLC).Separation was achieved on an Agilent TC-C₁₈ reversed-phase analytical column(5μm,6×150mm, I.D.).An Agilent TC-C₁₈ guard column(5μm,4.6×12.5mm,I.D.) was used to protect the analytical column.The mobile phase I for the analysis of IVM was methanol:water (90:10,v/v),at a flow rate of 1.0 mL/min,the injection volume was 20μL,elution was performed at an oven temperature of 30℃and IVM was determined by HPLC with UV detection at 245 nm.The mobile phaseâ…¡for the analysis of ABZSO was a solution of 1.25%triethylamine in acetonitrile:methanol:water(13:15:72,v/v/v),pH was adjusted to 3.1 using 85%o-phosphoric acid,at a flow rate of 1.0 mL/min,the injection volume was 20μL,elution was performed at an oven temperature of 40℃and IVM was determined by HPLC with UV detection at 290nm.Pharmacokinetics of IVM and ABZSO were investigated,following a single intramuscular administration at dose of 0.3mg/kg b.w. (28.94±2.67kg) in healthy pigs(n=6).The result showed that IVM concentration-time data was fitted to a one-compartment model with first order absorption.The absorption rate constant(K_a) of IVM was calculated to be 1.56±0.10d^-1,and the elimination half-life (t1/2ke) of the drug was 2.30±0.16d.The area under the serum concentration-time curve (AUC) was 120.86±6.98ng.mL^-1·d.The distribution volume(V_d/F) of lVM was computed to be 8.22±0.12L/kg.The total clearance of IVM(CL_b) was estimated to be 2.49±0.15L·d^-1·kg^-1 and the maximal plasma concentration(C_max) was calculated as 1.31±0.079d and 24.57±0.15ng/mL.Besides,the result showed that ABZSO concentration-time data was fitted to a two-compartment model with first order absorption.The absorption rate constant(K_a) of ABZSO was calculated to be K_a 0.43±0.09h^-1,and the elimination half-life(t1/2β) of the drug was 3.85±0.70h.The area under the serum concentration-time curve(AUC) was 24.37+3.62μg.mL^-1·h.The distribution volume(V_a/F) of ABZSO.was computed to be 1.18±0.17L/kg.The total clearance of ABZSO(CL_b) was estimated to be 0.21±0.03L·h^-1·kg^-1.The time-point of maximal plasma concentration of the drug(T_p) and the maximal plasma concentration (C_max) were calculated as 3.63±0.64h and 2.33±0.37μg/mL. The results of present studies revealed that IVM was absorbed fast,distributed extensively and eliminated slowly and ABZSO was absorbed fast,distributed extensively and eliminated fast in pigs.