Pharmacokinetics of a Long-Acting Formulation of Azithromycin in Pigs

The pharmacokinetics (PK) of a long acting 20% solution of azithromycin (AZ-LA) in pigs after a single peri-caudal injection at 10 and 20 mg/kg body weight was determined, using an aqueous formulation of the drug administered IV as reference, HPLC was used as analytical method. C-max was 1.4 and 2.5 mu g/mL, and T-max was 3.1 and 3.4 h, respectively for 10 and 20 mg/kg. Both preparations had 99.5% purity. Values for MRT were longer in the 10 mg/kg dose group (18.2 h) as compared to the 20 mg/kg group (16.5 h). Yet T1/2 beta was comparable between both dose levels (8.5 h vs. 7.2 h, for 10 and 20 mg/kg, respectively). No linear increments linked to dose were found in variables such as relative bioavailability, C-max and apparent volume of distribution. Values for relative bioavailability (Fr) of the higher dose as compared to the lower were 86.81% and absolute bioavailability (F) was 110.5 for the lower dose and 115.9% for the higher. Best PK/PD ratios for clinical efficacy of azithromycin describe this antibacterial drug as time-dependent. Considering pig's serum concentrations of the AZ-LA preparation here studied after its peri-caudal injection and based on a theoretical minimal therapeutic concentration in plasma of 0.1 mu g/mL based on bacteriological testing, a dose-interval of up to 48 h can be achieved. The suitability of this preparation to treat pig respiratory diseases is addressed. (C) 2014 PVJ. All rights reserved