Pharmacokinetics of ivermectin loaded PLA/PLGA microspheres suspension in dogs

【Objective】The pharmacokinetics of ivermectin (IVM) loaded in poly lactic acid (PLA) and Poly lactic-co-glycolic acid (PLGA) microspheres (MS) in dogs was investigated. 【Method】Eighteen healthy beagle dogs were divided into 3 groups randomly. PLA and PLGA MS suspensions (s.c) of IVM were given to the animals subcutaneously at a dosage of 3 mg·kg^-1 respectively. IVM (0.3 mg·kg^-1，s.c) was concluded in the experiment for comparison. The IVM concentration in dog plasma was determined by the reversed-phase HPLC, Pharmacokinetic parameters were estimated using the Winnonlin 5.2.1 software package.【Result and conclusion】The IVM concentration time data were fitted to noncompartment model. After subcutaneous administration of IVM（0.3 mg·kg^-1）injection the pharmacokinetic parameters were as follows: the peak concentration C_max was (44.3±5.1) ng·mL^-1, and t_max was (1.33±0.21) d; area under the curve AUC_0~∞ was (323.26±23.56) ng·mL^-1·d respectively.After subcutaneous injection of IVM-PLA-MS and IVM-PLGA-MS（3 mg·kg^-1）, area under the curve AUC_0~∞ was(1 041.47±73.73) and (1 461.77±102.54) ng·mL^-1·d respectively. PLA/PLGA MS suspensions of IVM have obviously a sustained-release property, with the plasma IVM concentration keeping in a steady state above 1 ng·mL^-1 for 140 days after administration.