Pharmacokinetic changes of several antibiotics in chickens during induced fatty liver

Abstract

The concentrations of five antibiotics (erythromycin, lincomycin, penicillin G, streptomycin and oxytetracycline) were determined in chicken serum before and after induced fatty liver. The pharmacokinetic variables were calculated according to the obtained data. The crossover trial design involved 10 chickens for each antibiotic. The fatty liver was produced by oestradiol-dipropionate injections and monitored by serum malic enzyme activity determinations. Protein binding of the respective antibiotics was determined in vitro in the serum obtained from normal and oestrogen-treated birds. Induction of fatty liver caused several changes in the determined variables. The measured peak concentrations were higher for lincomycin and erythromycin and lower for penicillin and oxytetracycline while streptomycin remained unchanged. The peak concentration of streptomycin appeared earlier and the peak of oxytetracycline later than in the normal chickens. The elimination half-lives were shorter for erythromycin, lincomycin and streptomycin and increased for penicillin and oxytetracycline. The area under the concentration curve (AUC) decreased for erythromycin, penicillin and streptomycin, increased for oxytetracycline and remained unchanged for lincomycin. The body clearance (ClB/f) and the apparent specific volume of distribution (Vd(area'/f) were considerably changed in association with fatty liver induction. Since the fraction of the drug absorbed (f) is not known, it can only be speculated that changes in distribution rather than reduced liver function altered the kinetics. The protein binding was decreased for all the antibiotics, but this did not seem to be the reason for changes in kinetics, except perhaps in the case of penicillin.