Penetration of amoxycillin 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 pleuropneumoniae infected pigs, after a single i.v. dose of 8.6 mg amoxycillin kg(-1) bodyweight. Pleuropneumoniae was produced experimentally in pigs by an aerosol infection model. The infection created a homogeneous response, characterised by depression of breathing and increased body temperature. The clinical symptoms were accompanied by increased haptoglobin 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 compartment open model. The mean residence time and the elimination half-life were 1.5 and 3.4 hours, respectively. The steady-state volume of distribution was 0.67 litres kg(-1), and the clearance was 0.46 litres kg(-1) hour(-1). There were no significant differences between these values and those reported previously for healthy pigs. The concentration of amoxycillin in bronchial secretions, lung tissue and diseased lung tissue peaked two hours after intravenous drug administration, while amoxycillin concentration in pleural fluid, lymph nodes and tonsil tissue peaked at the first sampling point one hour after drug administration. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than amoxycillin concentration in plasma, resulting in an increasing tissue-to-plasma concentration ratio. The distribution ratios (AUCtissue/AUCplasma) was 0.53 for bronchial secretions, 0.44 for pneumonic lung tissue, 0.42 for lung tissue, 1.04 for pleural fluid, 0.58 for lymph nodes and 0.37 for tonsil tissue. The distribution of amoxycillin to secretions was increased compared with that previously reported for healthy pigs, while only minor changes were observed in lung tissue.
Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark.
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H
Agersø
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C
Friis
J P
JP
Nielsen
D000189:Actinobacillus Infections / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D016977:Actinobacillus pleuropneumoniae; D000658:Amoxicillin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D014066:Palatine Tonsil / Q000378:metabolism; D010994:Pleura; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism / Q000503:physiopathology*
D000658:Amoxicillin