Comparing the pharmacokinetics of a fourth generation cephalosporin in three different age groups of New Forest ponies

Abstract

REASONS FOR PERFORMING STUDY To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. METHODS Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. RESULTS Both foal age groups had comparable pharmacokinetic data except for the volume of distribution at a steady-state (Vss), total body clearance (CIB) and mean residence time (MRT). Both ClB and MRT decreased as the age of the foals increased. Values of area under the curve increased, in a dose dependent manner, with significant increases for all age groups following administration of 4.5 mg/kg bwt q. 12 h. Total body clearance did not have comparable dose dependency. CONCLUSIONS Cefquinome can be given at a dose of 1 mg/kg bwt q. 12 h for the treatment of infections caused by susceptible pathogens with MIC <0.125 microg/ml. A higher dose of 4.5 mg/kg bwt q. 12 h is recommended for the treatment of bacterial pathogens with minimal inhibitory concentration (MIC) 0.125-0.5 microg/ml. POTENTIAL RELEVANCE Commonly used dosing regimens should be critically evaluated in neonatal foals due to the higher volume of distribution of less lipophilic drugs in this age group.