J. J. De Lucas

Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration

The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.

Pharmacokinetics of a single intravenous dose of marbofloxacin in adult donkeys

Six donkeys each received 2 mg/kg marbofloxacin as a 10 per cent aqueous solution administered intravenously. Principal pharmacokinetic parameters were determined and two efficacy indices were computed by using pharmacokinetic parameters and selected mic90 values of marbofloxacin against pathogenic equine strains to predict the efficacy of the drug at this dose. The pharmacokinetics of marbofloxacin in donkeys was characterised by a large mean volume of distribution at a steady state (1·15 [0·09] l/kg) and a long mean (sd) elimination half-life of 9·24 (1·96) hours. It was also characterised by a relatively slow total body clearance of 0·10 (0·02) l/kg/hour, slower than in horses. Using mic90 values of marbofloxacin against pathogenic equine strains with a daily dose of 2 mg/kg, appropriate values of efficacy indicators were obtained only for Enterobacteriaceae. Daily intravenous doses of 0·33, 2·62 and 20 mg/kg were calculated for evaluation in clinical trials of infections due to Enterobacteriaceae, Staphylococcus aureus and Streptococci, respectively.

Pharmacokinetics of enrofloxacin after multiple subcutaneous and intramuscular administrations in adult ostriches

1. The objective of the study was to evaluate the comparative pharmacokinetic behaviour of enrofloxacin in adult ostriches after single and multiple intramuscular (IM) and subcutaneous (SC) administrations. In addition, tissue tolerance was evaluated. 2. Enrofloxacin was well absorbed, but showed a short permanence after both administration routes. After multiple dose administrations the maximum and minimum peak plasma concentrations were very similar for both routes, obtaining a steady state phase from the second dose that extended until the last evaluated administration. 3. There was no significant accumulation after multiple IM or SC doses; however, there were differences in a fluctuation index after multiple intramuscular administrations that could be related to muscle damage. 4. The different microbiological efficacy indicators (PK/PD indices) obtained, the pharmacokinetic behaviour and CK serum concentrations suggest that subcutaneous enrofloxacin administration of 15 mg/kg every 12 h produce and maintain an efficient concentration of antibiotic that is a safer and more effective therapeutic option than intramuscular administration.

Ivermectin Residue Depletion in Food Producing Species and its Presence in Animal Foodstuffs With a View to Human Safety

From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 μg·kg(-1) in fat and liver and 30 μg·kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products.

Pharmacokinetics of marbofloxacin, after single intravenous administrations, in buffaloes calves

Abstract Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group which acts by inhibition of DNA gyrase and those acts by concentration dependant killing mechanism, so high plasma concentration initially is important. This drug is a fluoroquinolone developed exclusively for veterinary use, and exhibit high bactericidal activity against a broad spectrum of aerobic gram-negative, some gram-positive bacteria and Mycoplasma spp. The pharmacokinetic behaviour of marbofloxacin was investigated after intravenous (2 mg/kg) in five clinically healthy buffaloes (10 days-old). Plasma concentrations of the marbofloxacin were determined by a HPLC/ u.v. method. After intravenous administration, marbofloxacin in buffaloes was characterized by a AUC = 8,42±3,71 μg·h/ml, a large volume of distribution (Vss=1.59±0.55 L/kg) and a long persistence with an elimination half-life (t½λ) of 4.6±0,31 h, and MRT5,90±0,57h. Furthermore, marbofloxacin in buffaloes was characterized by a relatively low total body clearance (Cl) of 0.28±0.12 L/kg·h.

Pharmacokinetic interactions of marbofloxacin with anti-inflammatory drugs in buffalo calves

ANTIMICROBIAL agents are usually combined with NSAIDs to treat various systemic infections accompanied by fever and other inflammatory conditions. They can also be administered with steroidal anti-inflammatory drugs (SAIDs) to relieve suffering caused by inflammation. A pharmacological interaction between the two types of drug has been described in previous studies (Post and others 2002, 2003, Sidhu and others 2010, Ogino and others 2005). The combined use of anti-inflammatory and antimicrobial drugs is common clinical practice in young buffaloes due to enteric and respiratory infections, which are a significant problem and usually result in economic losses in nursing calves (Bukhari and others 2010). This short communication aimed to establish, in this species, the serum concentration-time profile and pharmacokinetic parameters of marbofloxacin (MBF), after intramuscular administration alone and in combination with intramuscular administration of ketoprofen (KPF), flunixin meglumine (FM) or dexamethasone (DXM), and to integrate pharmacokinetic/pharmacodynamic (PK/PD) data. Twenty-four, seven- to 15-day-old clinically healthy buffalo calves (mean [sd] weight 60.43 [6.75] kg) were included in the study and randomly allocated to one of four treatment groups. A parallel design was used, taking into account the age of the selected animals. All groups received a 2 mg/kg dose of MBF intramuscularly in the semitendinous muscle. The first group received only MBF, while the other three groups also received a dose of one of three drugs: 3 mg/kg KPF (MBF+KTF), 2.5 mg/kg FM (MBF+FM) or 0.1 mg/kg DXM (MBF+DXM) intramuscularly in the opposite semitendinous muscle. The study was approved by the Animal Experimentation Ethics Committee at the School of Veterinary Medicine, Universidad Nacional del Litoral, Argentina. Serum MBF concentrations were quantified using HPLC/ultraviolet (Waxman and others 2001). The quantification limit was 0.025 µg/ml and the method was linear up to 15 µg/ml. The mean (sd) precision …

Pharmacokinetics of marbofloxacin, after one bolus oral administration in buffaloes calves: Preliminary study.

Abstract Buffalo breeding system has a great economic importance in South-America, principally in marginal or sub-tropical lands. The therapeutic recommendations applied to a single ruminant species are extrapolated to others but important differences among those were recognized. Marbofloxacin bolus is indicated in the treatment of neonatal gastroenteritis caused by Escherichia coli, in calves (25-50kg). The aim of this study was determined the pharmacokinetic behaviour of marbofloxacin after oral administration, as bolus, following the label approved recommendations to cattle. One bolus (50 mg) was administered in two clinically healthy buffaloes (two days-old, 48-50kg). Plasma concentrations of the marbofloxacin were determined by a HPLC/u.v. method. After oral administration, the values obtained were: tmax=0.5-6h, Cmax= 1.19-0.04μg/mL, AUCt=1.57-0.38μg·h/mL and MRTt= 3.34-6.92h, for calves 1 and 2 respectively. Fluoroquinolones act by concentration dependant killing mechanism, so high plasma concentration initially is important. For this reason, the recommended dose of 1mg/kg is inadequate in buffaloes.