Pharmacokinetics And Pharmacodynamics Of Clindamycin In Swines And Its Clinical Application

Clindamycin hydrochloride is a semisynthetic lincosaminide that inhibits bacterial growth through impaired ribosomal protein synthesis .It has proved useful for the treatment of infections caused by Staphylococcus spp.and most anaerobic organisms.Currently clindamycin is approved for veterinary use in the United States only in dogs,although it is approved in some European countries for use in cats.But in our country clindamycin has not be collected into veterinary medicine dictionary. This paper dealt with efficacy evaluation of Clindamycin in swines.In vitro Inhibitory tests showed that the MICs of Clindamycin Lincomycin-. Ciprofloxacin and Gentamicin for Streptococcus C55121 respective were 0.01 6mg/L0.032mg7L arid 1.01 lmgIL and 8.7rng/L .Then the therapeutic trials ofClindamycin(Smg/kg 11 mg/kg2omg/kg),Lincomycin( 11 mg/kg)agains t experimentally induced Streptococcosis were carried out in swines following intramuscular administration for six days (only once daily), the curative rates of the infected swines were 0%-. 83.3%-. 100% 66.6%,respectively.The mortality of the infected and untreated group was 87.5%. In order to prepare a contagious disease model for pharmacokinetic and pharmacodymamics studies in swine ,96 hybrid pigs were used to develop a typical acute Streptococcosis suum by inoculating Subcutaneouisly 0.35 billion of pure living Streptococcus suis (C55121) to each animal for per weight.Just at the 1st day after conticnously than uninfected.The present model has theoretical and practical significances for the pharmacologists to investigate the disposition of drugs in infected swine,demonstrate the principles of the effects of contagious disease on pharmacokinetics of drugs and guide veterinarians how to use drugs reasonably in clmics,because it has the same general natures as other infectious diseases of swine clinically and pathologically,and also its development is reliable and repetitious under the same experimental conditions.A plasma sample (lml) was pipetted into OasisTMHLB spiked34with 1 Oul of internal standard,and loaded onto the silica extraction column.Each extraction column was preconditioned with one volume of methanol (about 1 ml) and one volume of deionized water (about lml).After loading the sample,the column was washed with lml solution of 5m1 methanol and 95m1 deionized which was added dropwise. The elutriates were collected when 1 ml methanol be used to wash and evaporated to dryness in a gentle stream of nitrogen.The presidue was reconstituted with 100 ul of mobile phase. An aliquot (20 ul ) was injected for HPLC analysis. Elution was achieved at ambient temperature with acetonitrile . tetrahydrofuran and 0.05M phosphate bulfer as the mobile phase .The flow-rate was set to 1 .Oml/min, UV-detector was operated at 2OSnnt. The pharmacokinetic of clindamycin was carried out in 5 healthy pigs and 5 infected pigs single IM administration at the dose of 11mg/kg body weight and the plasma concentration of clindamycin were determined in the conditions.The main pharmacokinetics parameters after IM administraiion were as follows in healthy pigs ~ 54643 ?0. 2242mg/L, T723. 21069h, AUC17. 86572?1. 2546mg/L ?h, T,,,~,2.18796?. 4437h0 In infected pigs Ce>,. 2. 55689?. 1245mg/L, T122.69123?. 8952h, AUC 12.00654?.2546mg?h/L, Tm~,, 1. 16176?.5436h0 So when a Streptococcosis disease be treated we should use a dose of 20mg/kg body weight.