Pharmacokinetics of danofloxacin following intravenous and intramuscular administration in donkeys

Abstract

Danofloxacin (DNF) is a synthetic antibacterial agent of thefluoroquinolone group, developed specifically for use in veteri-nary medicine. The drug possesses good in vitro activity against avariety of pathogens, including gram-positive and gram-negativebacteria, mycoplasmas, and intracellular pathogens, such asBrucella and Chlamdia species; but it has poor activity againstanaerobes (Wolfson & Hooper, 1985; Neu, 1987; McKellar et al.,1998; Aliabadi et al., 2003a).Danofloxacin shares with other fluoroquinolones, such asenrofloxacin and ciprofloxacin, a wide spectrum of activity, alarge volume of distribution and activity at low concentrations(Van Cutsem et al., 1990; Spreng et al., 1995; Brown et al.,1996). Pharmacokinetic properties of different fluoroquinol-ones have been extensively studied on several animal species(Knoll et al., 1999; Atef et al., 2001; Fernandez-Varon et al.,2006). In addition, some fluoroquinolones, such as DNF,moxifloxacin, marbofloxacin and enrofloxacin, are being usedwidely in horses (Bertone et al., 2000; Carretero et al., 2002;Gardner et al., 2004). Pharmacokinetic disposition of DNF hasbeen evaluated in many animal species including cattle, goats,sheep, camels, rabbit, chickens, turkeys, pig and horses (Knollet al., 1999; McKellar et al., 1999; Lindecrona et al., 2000;Atef et al., 2001; Aliabadi et al., 2003a,b; Shojaee Aliabadi L Haritova et al., 2006; Fernandez-Varon et al.,2006, 2007).There is a paucity of data available on the pharmacokineticsof drugs used in donkeys including antibiotics, as donkeys areoften neglected species in domestic animals. Different classes ofdrugs used in horses and ruminants are commonly extrapo-lated to donkeys without optimization of dosing regimens anddetermination of pharmacokinetic and pharmacodynamicproperties. Because of the lack of registered drugs for donkeys,antimicrobials licensed for horses or ruminants are used fortreatment of bacterial infections in this species with same doserates. In the literature, data are available only on thepharmacokinetics of gentamicin, sulfamethoxazole with tri-methoprim and marbofloxacin in donkeys (Welfare et al.,1996; Peck et al., 2002; Gonza´lez et al., 2007). It has beenreported that donkeys have a greater capacity to metabolizecertain drugs compared with horses; thus higher dosage orshorter intervals are required for maintaining effective con-centrations (Welfare et al., 1996; Matthews et al., 1997Coakley et al., 1999; Peck et al., 2002). Therefore, the aimof the present study was to determine the pharmacokineticproperties of DNF in donkeys following intravenous (i.v.) andintramuscular (i.m.) administration at single dose of1.25 mg⁄kg bodyweight.Six native breed donkeys (Equus asinus) which ranged in agefrom 2 to 5 years and weighted 90–125 kg were used in thisstudy. The animals were kept indoors and had clover hay andwater available ad libitum throughout the course of the study.This study was approved by Animal Ethic Committee ofUniversity of Adnan Menderes. The animals were allocated intotwo groups of three such that the mean weight of animals ineach group was similar and the donkeys were identified byunique freeze brand or natural markings. Danofloxacin wasadministered according to a two-phase crossover design proto-col. In phase I, group I received i.v. the commercially availableinjectable solution of DNF (Advocin , 2.5% w⁄v, Pfizer, Turkey)at a dose of 1.25 mg⁄kg bodyweight and group II received i.m.the same formulation at the same dose rate into gluteal muscle.A 2-week washout period was allowed between the two phases.Heparinized blood samples (5 mL) were collected 1 h prior todrug administration and 5, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6,8, 12, 24, 32, 36 and 48 h post-treatment. Blood samples werecentrifuged at 5000 g for 20 min and plasma was transferred toplastic tubes. All the plasma samples were stored at )20 C untilthe determination of drug concentration. In addition, serumsamples were also collected to determine creatin kinase (CK)activity after i.m. administration. The samples were stored at4 C for 2 h until CK activity (expressed in U⁄L), which wasmeasured preinjection and after i.m. injection using a commer-cial available kit (CK EE547; Linear Chemicals , Barcelona,Spain).