title: A pharmacokinetic study of amoxycillin in febrile beagle dogs following repeated administrations of endotoxin.
abstract: The pharmacokinetics of amoxycillin was studied in nine male beagle dogs under healthy and febrile conditions. In Period 1, dogs received 20 mg/kg of an oral suspension of amoxycillin. Intravenous doses of saline, 2 and 20 microg/kg of endotoxin (LPS from Escherichia coli serotype) were administered to dogs (three per group) prior to administration of 20 mg/kg of amoxycillin in Period 2. Rectal temperature and behavioral changes were recorded and blood samples were collected over 12 h for pharmacokinetic analysis. Amoxycillin was assessed in plasma using liquid chromatography coupled with mass spectrometry. Plasma concentrations were analysed using a one-compartment model with lag-time for absorption using an iterative two-stage method. As compared with control groups, amoxycillin clearance decreased significantly with preliminary treatments of 2 microg/kg endotoxin (0.209 vs. 0.140 L/h kg, P < 0.05) and 20 microg/kg endotoxin (0.214 vs. 0.075 L/h kg, P < 0.05). As a result of this, the area under curve for the 2 and 20 microg/kg endotoxin groups increased significantly 100.4 vs. 149.4 microg h/mL (P < 0.05) and 99.2 vs. 277.7 microg h/mL (P < 0.05), respectively. Other drugs currently used for the treatment of fever and septic shock should be re-evaluated using a febrile animal model to avoid improper dose administration.
authors.affiliation: MDS Pharma Services, Ville St-Laurent (Montreal), Quebec, Canada H4R 2N6.
authors.forename: J F
authors.initials: JF
authors.lastname: Marier
authors.forename: F
authors.initials: F
authors.lastname: Beaudry
authors.forename: M P
authors.initials: MP
authors.lastname: Ducharme
authors.forename: D
authors.initials: D
authors.lastname: Fortin
authors.forename: J P
authors.initials: JP
authors.lastname: Moreau
authors.forename: R
authors.initials: R
authors.lastname: Massé
authors.forename: P
authors.initials: P
authors.lastname: Vachon
mesh_terms: D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs / Q000378:metabolism*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D010406:Penicillins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D008070:Lipopolysaccharides; D010406:Penicillins; D000658:Amoxicillin