The influence of age and body weight gain on enrofloxacin pharmacokinetics in turkeys—Allometric approach to dose optimization

Abstract

Enrofloxacin is a concentration‐dependent antimicrobial used in bacterial infections in poultry. During a few months of a turkey's life, pharmacokinetics of drugs undergoes substantial changes which may compromise their efficacy due to variability in internal exposure (measured by area under the concentration–time curve, AUC). The aim of this study was to describe the effects of age on the pharmacokinetics of a single intravenous (i.v.) and oral administration of enrofloxacin at a dose of 10 mg/kg to turkeys. It was found that during a 2.5‐month‐long period of growth from 1.4 to 14.6 kg, the AUC after i.v. administration increased almost threefold due to a significant decrease in the body clearance (from a mean of 0.76–0.28 L hr−1 kg−1). Over the same period, the mean elimination half‐life was prolonged from 2.65 to 7.03 hr. Oral administration resulted in a similar trend in pharmacokinetic parameters. For both routes, formation of the major metabolite, ciprofloxacin, was marginal. Protein binding was not age‐dependent and never exceeded 50%. Body clearance, volume of distribution and elimination half‐life were subjected to an allometric analysis and a novel, nonlinear dosage protocol has been proposed to improve the internal exposure to the drug in different age groups of turkeys.

Pharmacokinetics and tissue residue of enrofloxacin in healthy,Eimeria-infected broiler chickens and those pre-treated with amprolium and toltrazuril

“…Enrofloxacin is indicated clinically for the treatment of gastroenteric, respiratory, urogenital and skin infections in pigs, calves, cattle, and poultry [ 5 , 6 ]. Several kinds of research were carried out for pharmacokinetics pattern of enrofloxacin in different species including pigs [ 7 ], rabbits [ 8 ], sheep [ 9 , 10 ], goats [ 11 ], horses [ 12 , 13 ], poultry [ 5 , 6 , 14 , 15 ], turkey [ 16 ] and Japanese quail [ 4 ] under normal conditions. Moreover, it has been reported that pharmacokinetics of enrofloxacin is altered when concurrent administration with albendazole in calves [ 17 ].…”

Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

“…The amount of scientific evidence supporting the role of growth in the change of antimicrobial PK in broiler chickens and turkeys is extensive [ 2 , 3 , 4 , 5 , 6 , 7 ]. It is clear that the internal exposure to antimicrobials in these birds changes according to the power law relation to BW [ 20 , 21 , 22 ] and may be responsible for the suboptimal response to treatment in young individuals [ 4 ].…”

“…As a result, a significant age-dependent decrease in the capability of the clearing organs to eliminate drugs is seen. Indeed, the difference between the total body clearance (CL) in different age groups may be even three-fold as shown for metronidazole [ 2 ] or enrofloxacin [ 4 ] in turkeys. Significant age-dependent drop in CL has also been described for florfenicol in broilers [ 3 ] as well as for amoxicillin [ 5 ], doxycycline [ 6 ] and sodium salicylate [ 7 ] in turkeys.…”

“…For antimicrobials, the consequences of this change may be profound as the same drug dose (relative to BW) will result in different effects in birds of different age. In young birds which clear the drug faster, there is a high risk of subtherapeutic concentrations, treatment failure and selection of resistant strains of bacteria [ 4 ]. This may contribute to the higher incidence of antimicrobial resistance reported in young birds [ 9 ].…”

“…Since the age-dependent change in CL follows the power-law relationship with BW and is quite predictable in broilers and turkeys, the mathematical function describing this relation may be easily incorporated into the non-linear dosage protocol following the concept of intra-species scaling of the dose [ 3 ]. In a series of recent papers we developed a non-linear dosage protocol for enrofloxacin [ 4 ] and later tested it in turkeys [ 14 ] to assess if the age-related variability in the internal exposure to the drug may be eliminated by this approach. It was found that the non-linear dosage allowed to decrease this variability by more than half for the intravenous (i.v.)…”