PENETRATION OF AMOXICILLIN TO THE RESPIRATORY-TRACT TISSUES AND SECRETIONS IN ACTINOBACILLUS-PLEUROPNEUMONIAE INFECTED-PIGS

The pharmokinetic properties of amoxycillin, and its penetration into respiratory tract tissue, were determined in 18 Actinobacillus pleurop neumoniae infected pigs, after a single i.v. dose of 8.6 mg amoxycilli n kg(-1) bodyweight. Pleuropneumoniae was produced experimentally in p igs by an aerosol infection model. The infection created a homogenous response, characterised by depression of breathing and increased body temperature. The clinical symptoms were accompanied by increased hapto globin levels and circulating white blood cell counts. At necropsy the findings were characterised by a bilateral fibrinous pleuropneumonia. Twenty hours after infection, the pigs were administered amoxycillin i.v. The plasma concentration-time curve was described by a three comp artment open model. The mean residence time and the elimination half-l ife were 1.5 and 3.4 hours, respectively. The steady-state volume of d istribution was 0.67 litres kg(-1), and the clearance was 0.46 litres kg(-1) hour(-1). There were no significant differences between these v alues and those reported previously for healthy pigs. The concentratio n of amoxycillin in bronchial secretions, lung tissue and diseased lun g tissue peaked two hours after intravenous drug administration, while amoxycillin concentration in pleural fluid, lymph nodes and tonsil ti ssue peaked at the first sampling point one hour after drug administra tion. The concentration of amoxycillin in secretions and tissue decrea sed by a slower rate than amoxycillin concentration in plasma, resulti ng in an increasing tissue-to-plasma concentration ratio. The distribu tion ratios (AUC(tissue)/AUC(plasma)) was 0.53 for bronchial secretion s, 0.44 for pneumonic lung tissue, 0.42 for lung tissue, 1.04 for pleu ral fluid, 0.58 for lymph nodes and 0.37 for tonsil tissue. The distri bution of amoxycillin to secretions was increased compared with that p reviously reported for healthy pigs, while only minor changes were obs erved in lung tissue.