Manuel I. San Andrés

HEMATOLOGICAL, PROTEIN ELECTROPHORESIS AND CHOLINESTERASE VALUES OF FREE-LIVING NESTLING PEREGRINE FALCONS IN SPAIN

Protein electrophoresis, hematological and cholinesterase values were determined in 32 nestling free-living peregrine falcons (Falco peregrinus) (15- to 27-days-old) in order to establish normal reference values for this population. The following values (mean ± SD) were observed: prealbumin 0.31 ± 0.04 g/dl, albumin 1.25 ± 0.06 g/dl, α1 and α2-globulin 0.23 ± 0.02 and 0.16 ± 0.02 g/dl respectively, β-globulin 1.02 ± 0.05 g/dl, γ-globulin 0.060 ± 0.08 g/dl, total protein 3.79 ± 0.18 g/dl, 21.26 ± 1.30 white blood cells/μl (1 × 103), 2.17 ± 0.07 red blood cells/μl (1 × 106), packed cell volume 37.58 ± 0.82%, hemoglobin 20.96 ± 0.29 g/dl, heterophils 61.14 ± 2.50% and cholinesterase 1,184 ± 75 IU/L. There were no difference in any of these parameters among males and females. The hematological values obtained could be considered as representative values in free-living nestling peregrine falcons.

Hematologic, protein electrophoresis, biochemistry, and cholinesterase values of free-living black stork nestlings (Ciconia nigra).

Hematologic, protein electrophoresis, serum biochemistry, and cholinesterase values were determined in 36 free-living black stork nestlings (Ciconia nigra) between 25 and 53 days of age in order to establish normal reference values for this population. The following values were evaluated: white blood cell counts, red blood cell counts, packed cell volume, hemoglobin, heterophils, lymphocytes, monocytes, eosinophils, prealbumin, albumin, α -globulin, β-globulin, γ-globulin, total protein, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, calcium, phosphorus, iron, cholesterol, glucose, triglycerides, uric acid, urea, creatinine, total solids, bile acids, and butyrylcholinesterase. Sex-dependent differences were observed in hemoglobin, prealbumin, albumin, γ-globulin, total protein, alkaline phosphatase, and triglycerides. Packed cell volume, butyrylcholinesterase, aspartate aminotransferase, creatine kinase, and creatinine increased with age, whereas albumin, mean cell volume, calcium, phosphorus, cholesterol, and total solids decreased with age. These hematologic and serum biochemistry values can be used as reference ranges in free-living black stork nestlings.

Pharmacokinetic profile of ivermectin in cattle dung excretion, and its associated environmental hazard.

Ivermectin is a worldwide used antiparasitic compound acting against both endo- and ecto parasites of livestock. Ivermectin can reach the environment through the direct emission of dung from livestock on pasture and via manure application on agricultural lands. Due to its very high acute toxicity to many invertebrates, especially to D. magna, the excretion profile of ivermectin in dung after application is essential for assessing its potential effects on terrestrial and aquatic ecosystems. The aim of this article is to characterize the excretion profile, comparing plasma and dung levels, after a single subcutaneous dose to cattle, to be used in environmental risk assessment. The cumulative curve of excreted ivermectin was used to calculate the PEC dung in manure to be used as fertilizer. The potential hazard for dung fauna, aquatic and soil organism is presented through the combination of toxicity and excretion levels. Three hazard levels, offering the relevant information to veterinarians prescribing the drug, are presented.

Pharmacokinetics of Marbofloxacin After Oral Administration to Eurasian Buzzards (Buteo buteo)

Abstract Marbofloxacin is a bactericidal fluoroquinolone developed exclusively for veterinary medicine. The pharmacokinetic disposition of this drug was studied after oral administration of a single dose (10 mg/kg) to 8 adult Eurasian buzzards (Buteo buteo). Plasma concentrations of marbofloxacin were measured during the 48-hour period after drug administration. A maximum plasma concentration of 3.70 μg/ml was achieved at 2.92 hours. Marbofloxacin was relatively slowly absorbed after oral administration (absorption half-life of 1.57 hours) and demonstrated a high bioavailability (92.15%). The elimination half-life was 9.48 hours, and the mean residence time was 10.65 hours. When using a minimum inhibitory concentration (MIC) breakpoint of 0.25 μg/ml, the calculated antimicrobial efficacy of orally administered marbofloxacin was higher than the range considered optimal for a dosing regimen against pathogens with an equivalent MIC. A dosage of 10 mg/kg administered once daily appears to be appropriate for the treatment of most infections with gram-negative bacteria that affect Eurasian buzzards.

Marbofloxacin disposition after intravenous administration of a single dose in wild mallard ducks (Anas platyrhynchos).

Abstract Marbofloxacin, a fluoroquinolone developed specifically for veterinary use, has demonstrated considerable pharmokinetic variation among avian species. The goal of this study was to determine the disposition kinetics of marbofloxacin in mallard ducks (Anas platyrhynchos) after a single intravenous injection. Six wild mallard ducks were used in the study. Marbofloxacin was injected at a dose of 2 mg/kg into the basilic vein, and blood was subsequently collected at regular intervals from each bird. Plasma marbofloxacin concentrations were determined by using high-performance liquid chromatography. The volume of distribution at steady state was 1.78 ± 0.37 L/kg, and the total plasma clearance was 0.59 ± 0.08 L/kg per hour. Marbofloxacin had a relatively short permanence, with a elimination half-life of 2.81 ± 1.20 hours, a terminal half-life of 2.43 ± 0.61 hours, and a mean residence time of 2.99 ± 0.52 hour. The maximum observed concentration (Cmax) and area under the curve (AUC) were 1.34 ± 0.27 µg/mL and 3.75 ± 0.56 µg · h/mL, respectively. Values of minimum inhibitory concentration (MIC), Cmax, and AUC have been used to predict the clinical efficacy of a drug in treating bacterial infections, with a Cmax ∶ MIC value of 10 and an AUC ∶ MIC ratio of 125–250 associated with optimal bactericidal effects. By using the study data and MIC breakpoints of 0.125 µg/mL or 0.2 µg/mL, values derived for Cmax ∶ MIC were 9.37 ± 0.99 and 5.85 ± 0.62, respectively, and for AUC ∶ MIC were 29.99 ± 4.51 and 18.74 ± 2.82, respectively. By using MIC values of 0.125 and 0.2 µg/mL and a target AUC ∶ MIC  =  125, the calculated optimal daily marbofloxacin dosages for mallard ducks were 9.24 and 14.78 mg/kg, respectively. These results suggest that, primarily because of the high total plasma clearance observed, the marbofloxacin dose for treatment of bacterial diseases in mallard ducks should be increased after intravenous administration. Intravenous doses of 10–15 mg/kg should be assessed by studying their potential toxicity and efficacy in sick birds.

Pharmacokinetic and Pharmacodynamic Properties of Enrofloxacin in Southern Crested Caracaras (Caracara plancus)

Abstract: To determine the dosage of enrofloxacin in southern crested caracaras (Caracara plancus), plasma concentrations of enrofloxacin were measured by high-performance liquid chromatography after intravenous (IV) (5 mg/kg) and intramuscular (IM) (10 mg/kg) administration. This compound presented a relatively high volume of distribution (2.09 L/kg), a total body clearance of 0.24 L/kg·h, and a long permanence as shown by an elimination half-life of 7.81 hours after IV administration and a terminal half-life of 6.58 hours after IM administration. The areas under the concentration-time curves (AUC) were 21.92 and 34.38 μg·h/mL for IM and IV administration, respectively. Enrofloxacin was rapidly absorbed after IM administration with a time to reach maximum concentration of 0.72 hours and bioavailability of 78.76%. After IM administration, the peak drug concentration (Cmax) was 3.92 μg/mL. Values of minimum inhibitory concentration (MIC), Cmax, and AUC have been used to predict the clinical efficacy of a drug in treating bacterial infections, with a Cmax/MIC value of 10 and an AUC/MIC ratio of 125–250 associated with optimal bactericidal effects. By using the study data and a MIC breakpoint of 0.25 μg/mL, values of Cmax/MIC were 13.74 and 15.94 and for AUC/MIC were 90.73 and 139.63, for the IV and IM routes respectively. For the treatment of infectious diseases caused by microorganisms with MIC ≤0.25 μg/mL, the calculated optimal dosages were 7.5 and 9.5 mg/kg q24h by the IV and IM routes, respectively. For less susceptible bacteria, a dose increase should be evaluated. To treat caracara by the IV route against microorganisms with MIC ≤0.25 μg/mL, the dose should be higher than the 5 mg/kg used in our study, but possible side effects derived from an increase in the IV dose and efficacy in sick birds should be assessed.

Use of cholinesterase activity in monitoring chlorpyrifos exposure of steer cattle after topical administration

The aim of this work was to study the pharmacokinetic behavior and the inhibitory effect of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of chlorpyrifos (CPF) in steer cattle after pour-on administration. Determination of cholinesterase activity in plasma and erythrocyte was carried out according to Ellman kinetic method. CPF was analyzed by gas chromatography. AChE was the predominant form of cholinesterase analyzed, with low levels of BChE in plasma. Following the treatment with CPF, the maximum inhibitory effect on AChE or BChE were 50.88 ± 11.57 and 42.66 ± 12.01%, respectively. The chlorpyrifos plasma concentrations observed were low and they presented a high variability. Chlorpyrifos peak plasma concentration (10.42 ± 4.76 μ g/L) was reached at 8.42 ± 13.97 h. The pesticide was not detected in plasma after 48 h post treatment. The values of area under the curve (AUC) were 118.48 ± 87.46 μ g· h/L and mean resistance time (MRT) were 13.38 ± 10.41 h. The pour-on exposure to the organophosphate chlorpyrifos significantly reduced AChE and BChE activity in steer cattle and the recovery was not reached on 50 days post-treatment.

PHARMACOKINETIC BEHAVIOR OF ENROFLOXACIN AND ITS METABOLITE CIPROFLOXACIN IN URUTU PIT VIPERS (BOTHROPS ALTERNATUS) AFTER INTRAMUSCULAR ADMINISTRATION

Abstract: Enrofloxacin is widely used in veterinary medicine and is an important alternative to treating bacterial infections, which play an important role as causes of disease and death in captive snakes. Its extralabel use in nontraditional species has been related to its excellent pharmacokinetic and antimicrobial characteristics. This can be demonstrated by its activity against gram-negative organisms implicated in serious infectious diseases of reptile species with a rapid and concentration-dependent bactericidal effect and a large volume of distribution. Pharmacokinetic parameters for enrofloxacin were investigated in seven urutu pit vipers (Bothrops alternatus), following intramuscular injections of 10 mg/kg. The plasma concentrations of enrofloxacin and its metabolite, ciprofloxacin, were measured using high-performance liquid chromatography. Blood samples were collected from the ventral coccygeal veins at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 108, and 168 hr. The kinetic behavior was characterized by a relatively slow absorption (time of maximal plasma concentration = 4.50 ± 3.45 hr) with peak plasma concentration of 4.81 ± 1.12 μg/ml. The long half-life during the terminal elimination phase (t1/2λ = 27.91 ± 7.55 hr) of enrofloxacin after intramuscular administration, calculated in the present study, could suggest that the antibiotic is eliminated relatively slowly and/or the presence of a slow absorption in urutu pit vipers. Ciprofloxacin reached a peak plasma concentration of 0.35 μg/ml at 13.45 hr, and the fraction of enrofloxacin metabolized to ciprofloxacin was 13.06%. If enrofloxacins minimum inhibitory concentration (MIC90) values of 0.5 μg/ml were used, the ratios AUCe+c : MIC90 (276 ± 67 hr) and Cmaxe+c : MIC90 (10 ± 2) reach the proposed threshold values (125 hr and 10, respectively) for optimized efficacy and minimized resistance development when treating infections caused by Pseudomonas. The administration of 10 mg/kg of enrofloxacin by the i.m. route should be considered to be a judicious choice in urutu pit vipers against infections caused by microorganisms with MIC values ≤0.5 μg/ml. For less susceptible bacteria, a dose increase and/or an interval reduction should be evaluated.

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 …

Comparison of pharmacokinetics of marbofloxacin after subcutaneous administration of various multiple-dose regimens to water buffalo calves (Bubalus bubalis).

OBJECTIVE To determine pharmacokinetics of marbofloxacin in water buffalo calves (Bubalus bubalis) after multiple SC administrations and to assess differences in regimen efficacy. ANIMALS 18 healthy buffalo calves. PROCEDURES Calves (n = 6 calves/group) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages (2 mg/kg, q 24 h for 6 days [regimen 1]; 4 mg/kg, q 48 h for 6 days [regimen 2]; and 4 mg/kg, q 24 h for 3 days [regimen 3]). Serum marbofloxacin concentrations were analyzed. Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica. RESULTS Mean ± SD area under the concentration-time curve was 5.92 ± 0.40 μg•h/mL for regimen 1, which differed significantly from that for regimens 2 (14.26 ± 0.92 μg•h/mL) and 3 (14.17 ± 0.51 μg•h/mL). Mean residence time and mean elimination half-life for regimen 2 (9.93 ± 0.20 hours and 8.77 ± 0.71 hours) both differed significantly from those for regimens 1 (721 ± 0.11 hours and 5.71 ± 0.38 hours) and 3 (759 ± 0.13 hours and 737 ± 1.19 hours). Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility (low, medium, and high) of the strains. CONCLUSIONS AND CLINICAL RELEVANCE Regimen 3 had the most favorable indices, and it would be conducive for owner compliance and require less handling of animals.