Pharmacokinetics of a combination preparation of ampicillin and sulbactam in turkeys

Abstract

Objective - To investigate the disposition kinetics of ampicillin and sulbactam after IV and IM administration of an ampicillin-sulbactam (2:1) preparation and determine the bioavailability of the combined preparation after IM administration in turkeys. Animals - 10 healthy large white turkeys. Procedure - In a crossover study, turkeys were administered the combined preparation IV (20 mg/kg) and IM (30 mg/kg). Blood samples were collected before and at intervals after drug administrations. Plasma ampicillin and sulbactam concentrations were measured by use of high-performance liquid chromatography; plasma concentration-time curves were analyzed via compartmental pharmacokinetics and noncompartmental methods. Results - The drugs were distributed according to an open 2-compartment model after IV administration and a 1-compartment model (first-order absorption) after IM administration. For ampicillin and sulbactam, the apparent volumes of distribution were 0.75 ± 0.11 L/kg and 0.74 ± 0.10 L/kg, respectively, and the total body clearances were 0.67 ± 0.07 L·kg-1·h-1 and 0.56 ± 0.06 L·kg-1·h-1, respectively. The elimination half-lives of ampicillin after IV and IM administration were 0.78 ± 0.12 hours and 0.89 ± 0.17 hours, respectively, whereas the corresponding half-lives of sulbactam were 0.91 ± 0.12 hours and 0.99 ± 0.16 hours, respectively. Bioavailability after IM injection was 58.87 ± 7.65% for ampicillin and 53.75 ± 5.35% for sulbactam. Conclusions and Clinical Relevance - Results indicated that a regimen of loading and maintenance doses of 300 mg of the ampicillin-sulbactam (2:1) combination/kg every 8 hours could be clinically useful in turkeys. This dosage regimen maintained plasma concentrations of ampicillin > 0.45 μg/mL in turkeys.