The influence of growth and E. coli endotoxaemia on amoxicillin pharmacokinetics in turkeys.

1. This experiment aimed to determine if the pharmacokinetics of amoxicillin (AMO) was affected by rapid growth or intravenous (i.v.) injection of Escherichia coli lipopolysaccharide (LPS). 2. Turkeys of 2.0, 5.5 and 12.0 kg were administered i.v. or orally with AMO sodium at the dose of 15 mg/kg. Another group (5.7 kg) was treated with LPS prior to i.v. AMO administration. Plasma drug concentrations were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using a non-compartmental model. To assess the haemodynamic effects of endotoxaemia, turkeys were subjected to echocardiography. 3. During growth from 2.0 to 5.5 kg, the area under the drug concentration-time curve after i.v. AMO administration increased from 9.37 ± 2.43 to 21.29 ± 5.49 mg×h/ml. Total body clearance decreased from 1.72 ± 0.55 to 0.75 ± 0.12 l/h/kg. Growth to 12.0 kg did not further affect these parameters. Mean residence time and elimination half-life gradually increased. Pharmacokinetics of orally administered drug followed a similar pattern. LPS injection affected stroke volume, heart rate and resistance index. However, it did not affect the pharmacokinetic profile of AMO in survivors. 4. It is concluded that rapid growth in turkeys affects AMO pharmacokinetics. Endotoxaemia, on the other hand, does not affect AMO elimination if compensatory mechanisms develop.