Acute-phase Response Alters the Disposition Kinetics of Cefepime following Intravenous Administration to Rabbits

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 × 10⁸ cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 μg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1^°C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level–time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V _dss) and body clearance (CL_tot) were affected in febrile as compared to healthy animals. The mean values of V _dss and CL_tot of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V _dss (0.917 L/kg) and CL_tot (0.205 L/kg per h) of cefepime were significantly lower, whereas t _1/2λ, MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.     

Influence of <Emphasis Type="Italic">E. coli</Emphasis> lipopolysaccharide induced fever on the plasma kinetics of cefepime in cross-bred calves

The pharmacokinetic behavior of cefepime was studied in healthy and febrile cross-bred calves after single intravenous administration (10 mg/kg). The fever was induced with E. coli lipopolysaccharide (1 μg/kg, IV). The drug concentration in plasma was detected by microbiological assay method using E. coli (MTCC 739) test organism. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by 2 compartment open model. At 1 min the concentration of cefepime in healthy and febrile animals were 55.3 ± 0.54 μg/ml and 50.0 ± 0.48 μg/ml, respectively and drug was detected up to 12 h. The elimination half-life of cefepime was increased from 1.26 ± 0.01 h in healthy animals to 1.62 ± 0.09 h in febrile animals. Drug distribution was altered by fever as febrile animals showed volume of distribution (0.27 ± 0.02 L/kg) higher than normal animal (0.19 ± 0.01 L/kg). Total body clearances in healthy and febrile animals were 104.4 ± 2.70 and 114.2 ± 1.20 ml/kg/h, respectively. To maintain minimum therapeutic concentration of 1 μg/ml, a satisfactory dosage regimen of cefepime in healthy and febrile cross-bred calves would be 15.5 mg/kg and 8.2 mg/kg body weight, respectively, to be repeated at 8 h intervals. The T>MIC values (8 h) of cefepime suggested that this agent is clinically effective in the treatment of various infections.     

Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).     

Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits

Gentamycin sulphate ( ) and gentamycin oleate ( ) were encapsulated in liposomes composed of phosphatidylcholine ( ) and cholesterol ( ) (molar ratio 7:7:2 and 5:5:l, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg⁻¹ of i.v., 3 mg kg⁻¹ of i.m., 3 mg kg⁻¹ of liposome-containing gentamycin sulphate ( ) i.m., 3 mg kg⁻¹ of i.m., and 3 mg kg⁻¹ of liposome-containing gentamycin oleate ( ) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of ; the peak plasma concentration ( _max) showed an eight-fold decrease with , and the area under the concentration-time curve ( ) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of showed a three-fold increase compared with values calculated for free . After the administration of the same dose of , _max obtained showed a 2·5-fold decrease in relation to peak concentrations of free , and the apparent β-half life of encapsulated showed a three-fold increase compared with i.m. . Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.     

Quantitation of meloxicam in the plasma of koalas (Phascolarctos cinereus) by improved high performance liquid chromatography

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C₁₈ 4-µm (300 × 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r² > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-µL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.     

Pharmacokinetics and bioavailability of chloramphenicol in normal and febrile goats

The effect of induced fever on the plasma concentrations and disposition kinetics of chloramphenicol (CHPC) was studied in adult goats. Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.1 microgram/kg, i.v.) and repeating it at half the dose (0.05 microgram/kg) 8 h later. Pharmacokinetics of CHPC was studied in both normal (n = 6) and febrile (n = 6) animals following intravenous administration of CHPC Na-succinate (25 mg/kg). Intramuscular bioavailability of the drug was also investigated in both normal and febrile animals. Pharmacokinetics of CHPC following intravenous administration could be described by a two-compartment open model in both normal and febrile animals. In normal animals the half-life of CHPC was 73.0 +/- 4.95 min and the volume of distribution was 2.217 +/- 0.24 l/kg. These and other pharmacokinetic parameters did not differ significantly (P less than 0.05) between normal and febrile animals, except for Cop and A. Absorption of CHPC following intramuscular administration was good as indicated by its high bioavailability in both normal (83.34%) and febrile (81.98%) animals. Volume of distribution is usually expected to change when the febrile state is induced. Lack of such an effect in the present study could be due to high individual variation, or to the fact that CHPC already has a relatively large volume of distribution, which is less likely to be altered by a febrile state of short duration.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats

The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t_1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd_(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd_(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 µg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.     

Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs

The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs. Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs. Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse-phase high-performance liquid chromatography (HPLC). Cefepime concentrations in both groups of animals were described by a two-compartment pharmacokinetic model with elimination half-lives of 1.65 and 1.09 h for the foal and dog, respectively. We tested whether or not pharmacokinetic parameters for cefepime could be scaled across species using principles of allometry. The parameters of elimination half-life (t(1/2)beta), apparent volume of distribution (VDarea), and systemic clearance (CL) were scaled linearly to body weight on a double logarithmic plot with allometric exponents for body weight of 0.26, 1.08 and 0.72, respectively. This study further determined doses for cefepime, a potentially useful antibiotic for neonatal foals and dogs, from the pharmacokinetic values. An i.v. dose of cefepime estimated from this study for treating sensitive bacteria was 11 mg/kg every 8 h for neonatal foals and 40 mg/kg every 6 h for dogs.     

Effects of Alkalinization and Rehydration on Plasma Potassium Concentrations in Neonatal Calves with Diarrhea

Background

Increased plasma potassium concentrations (K⁺) in neonatal calves with diarrhea are associated with acidemia and severe clinical dehydration and are therefore usually corrected by intravenous administration of fluids containing sodium bicarbonate.

Objectives

To identify clinical and laboratory variables that are associated with changes of plasma K⁺ during the course of treatment and to document the plasma potassium‐lowering effect of hypertonic (8.4%) sodium bicarbonate solutions.

Animals

Seventy‐one neonatal diarrheic calves.

Methods

Prospective cohort study. Calves were treated according to a clinical protocol using an oral electrolyte solution and commercially available packages of 8.4% sodium bicarbonate (250–750 mmol), 0.9% saline (5–10 L), and 40% dextrose (0.5 L) infusion solutions.

Results

Infusions with 8.4% sodium bicarbonate solutions in an amount of 250–750 mmol had an immediate and sustained plasma potassium‐lowering effect. One hour after the end of such infusions or the start of a sodium bicarbonate containing constant drip infusion, changes of plasma K⁺ were most closely correlated to changes of venous blood pH, plasma sodium concentrations and plasma volume (r = −0.73, −0.57, −0.53; P < .001). Changes of plasma K⁺ during the subsequent 23 hours were associated with changes of venous blood pH, clinical hydration status (enophthalmos) and serum creatinine concentrations (r = −0.71, 0.63, 0.62; P < .001).

Conclusions and Clinical Importance

This study emphasizes the importance of alkalinization and the correction of dehydration in the treatment of hyperkalemia in neonatal calves with diarrhea.     

The construction and application of a population physiologically based pharmacokinetic model for methadone in Beagles and Greyhounds

Methadone is an opioid analgesic in veterinary and human medicine. To help develop appropriate pain management practices and to develop a quantitative model for predicting methadone dosimetry, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model for methadone in dogs constructed with Berkeley Madonna? was developed. The model accounts for intravenous (IV), subcutaneous (SC), and oral administrations, and compartmentalizes the body into different components. This model was calibrated from plasma pharmacokinetic data after IV administration of methadone in Beagles and Greyhounds. The calibrated model was evaluated with independent data in both breeds of dogs. One advantage of this model is that most physiological parameter values for Greyhounds were taken directly from the original literature. The developed model simulates available pharmacokinetic data for plasma concentrations well for both breeds. After conducting regression analysis, all simulated datasets produced an R ² > 0.80 when compared to the measured plasma concentrations. Comparative analysis of the dosimetry of methadone between the breeds suggested that Greyhounds had ~50% lower 24‐hr area under the curve (AUC) of plasma or brain concentrations than in Beagles. Furthermore, population analysis was conducted with this study. This model can be used to predict methadone concentrations in multiple dog breeds using breed‐specific parameters.     

Pathogen translocation and histopathological lesions in an experimental model of Salmonella Dublin infection in calves receiving lactic acid bacteria and lactose supplements

The purpose of this study was to evaluate the capacity of a lactic acid bacteria (LAB) inoculum to protect calves with or without lactose supplements against Salmonella Dublin infection by evaluating histopathological lesions and pathogen translocation. Fifteen calves were divided into three groups [control group (C-G), a group inoculated with LAB (LAB-G), and a group inoculated with LAB and given lactose supplements (L-LAB-G)] with five, six, and four animals, respectively. The inoculum, composed of Lactobacillus (L.) casei DSPV 318T, L. salivarius DSPV 315T, and Pediococcus acidilactici DSPV 006T, was administered with milk replacer. The LAB-G and L-LAB-G received a daily dose of 10⁹ CFU/kg body weight of each strain throughout the experiment. Lactose was provided to the L-LAB-G in doses of 100 g/day. Salmonella Dublin (2 × 10¹⁰ CFU) was orally administered to all animals on day 11 of the experiment. The microscopic lesion index values in target organs were 83%, 70%, and 64.3% (p < 0.05) for the C-G, LAB-G, and L-LAB-G, respectively. Administration of the probiotic inoculum was not fully effective against infection caused by Salmonella. Although probiotic treatment was unable to delay the arrival of pathogen to target organs, it was evident that the inoculum altered the response of animals against pathogen infection.     

Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs

Background

Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications.

Hypothesis/Objectives

To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs.

Animals

Eight healthy research dogs.

Methods

Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H₂O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling.

Results

Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H₂O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H₂O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects.

Conclusions and Clinical Importance

The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H₂O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration.     

Myeloid differentiation factor 88 is required for resistance to Neospora caninum infection

Neospora caninum is an intracellular parasite that causes major economic impact on cattle raising farms, and infects a wide range of warm-blooded hosts worldwide. Innate immune mechanisms that lead to protection against this parasite are still unknown. In order to investigate whether myeloid differentiation factor 88 (MyD88) is required for resistance against N. caninum, genetically deficient mice (MyD88^−/−) and wild type littermates were infected with live tachyzoites and the resistance to infection was evaluated. We found that sub-lethal tachyzoite doses induced acute mortality of MyD88^−/− mice, which succumbed to infection due to uncontrolled parasite replication. Higher parasitism in MyD88^−/− mice was associated with the lack of IL-12 production by dendritic cells, delayed IFN-γ responses by NKT, CD4⁺ and CD8⁺ T lymphocytes, and production of high levels of IL-10. MyD88^−/− mice replenished with IL-12 and IFN-γ abolished susceptibility as the animals survived throughout the experimental period. We conclude that protective IFN-γ-mediated immunity to N. caninum is dependent on initial MyD88 signaling, in a mechanism triggered by production of IL-12 by dendritic cells. Further knowledge on Toll-like receptor recognition of N. caninum antigens is encouraged, since it could generate new prophylactic and therapeutic tools to control parasite burden.     

Efficacy of strain RB51 vaccine in protecting infection and vertical transmission against Brucella abortus in Sprague-Dawley rats

Immunizing animals in the wild against Brucella (B.) abortus is essential to control bovine brucellosis because cattle can get the disease through close contact with infected wildlife. The aim of this experiment was to evaluate the effectiveness of the B. abortus strain RB51 vaccine in protecting infection as well as vertical transmission in Sprague-Dawley (SD) rats against B. abortus biotype 1. Virgin female SD rats (n = 48) two months of age were divided into two groups: one group (n = 24) received RB51 vaccine intraperitoneally with 3 × 10¹⁰ colony forming units (CFU) and the other group (n = 24) was used as non-vaccinated control. Non-vaccinated and RB51-vaccinated rats were challenged with 1.5 × 10⁹ CFU of virulent B. abortus biotype 1 six weeks after vaccination. Three weeks after challenge, all rats were bred. Verification of RB51-vaccine induced protection in SD rats was determined by bacteriological, serological and molecular screening of maternal and fetal tissues at necropsy. The RB51 vaccine elicited 81.25% protection in SD rats against infection with B. abortus biotype 1. Offspring from rats vaccinated with RB51 had a decreased (p < 0.05) prevalence of vertical transmission of B. abortus biotype 1 compared to the offspring from non-vaccinated rats (20.23% and 87.50%, respectively). This is the first report of RB51 vaccination efficacy against the vertical transmission of B. abortus in the SD rat model.     

Plasma drug concentrations and clinical effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in horses sedated with detomidine

ObjectiveTo investigate plasma drug concentrations and the effect of MK-467 (L-659′066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.Study designExperimental randomized blinded crossover study.AnimalsSix healthy horses.MethodsDetomidine (10 μg kg^?1 IV) was administered alone (DET) and in combination with MK-467 (250 μg kg^?1 IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUC_sed) and pharmacokinetic parameters. Significance was set at p < 0.05.ResultsA significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUC_sed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.Conclusions and clinical relevanceMK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.     

Reliability of the i‐STAT for the determination of blood electrolyte (K+, Na+, and CI−) concentrations in cattle

Background

Rapid determination of blood electrolyte concentrations can help determine electrolyte status and delivery of effective volume of electrolyte solutions in field conditions.

Objective

To evaluate reliability of the i‐STAT, a point‐of‐care (POC) device, in measuring blood K⁺, Na⁺, and CI ⁻ concentrations in cattle.

Animals

Ninety‐eight cattle with various diseases.

Methods

In this prospective study, blood samples collected from the jugular vein were processed for determination of K⁺, Na⁺, and CI ⁻ concentrations in blood and plasma using the i‐STAT and auto‐analyzer (Cobas C501), respectively. Blood and plasma electrolyte data were subjected to student t‐test for comparison, the concordance analysis for agreement, accuracy, and precision, the Passing‐Bablok regression and the Bland‐Altman plot for reliability, and receiver operating characteristics curves for sensitivity (Se) and specificity (Sp).

Results

Plasma concentrations of K⁺ (4.39 versus 4.2 mmol/L; P < .0001) and CI ⁻ (100.30 versus 99.4 mmol/L; P < .04) were greater than their concentrations in blood. Plasma and blood Na⁺ concentrations were similar (136.95 versus 136.8 mmol/L). The i‐STAT results were highly correlated with the Cobas C501 results (r = 0.970, 0.922, and 0.866 for K⁺, Na⁺, and CI ⁻, respectively). Regression equations fitting blood (Y) and plasma (X) concentration did not deviate from the identity line for K⁺ (Y = −0.10 + 0.98 × X), Na⁺ (Y = X), and CI ⁻ (Y = 3.04 + 0.96 × X). The mean bias (blood concentration ‐ plasma concentration) was −0.20 for K⁺ (P = .03), −0.16 for Na⁺ (P = .12), and −0.87 for CI ⁻ (P = .93). The i‐STAT had 76–100% Se and 87.7–100% Sp for assessing electrolyte statuses.

Conclusions and Clinical Importance

The i‐STAT yielded results that were in agreement with the auto‐analyzer, with negligible biases in measurement of plasma K⁺, Na⁺, and CI ⁻ concentrations. The i‐STAT is a reliable POC device and can be used in field condition to assess electrolyte status in cattle.     

Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t _1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t _1/2el), mean residence time, and maximum plasma concentration ( C _max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C _max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.     

Leishmania infantum in wild animals in endemic areas of southern Italy

Leishmania infantum infection in wildlife is increasingly reported in Europe, but scant data are available in Italy so far. This study aimed to investigate the circulation of L. infantum among sylvatic hosts in Sicily (southern Italy), a highly endemic area for canine leishmaniosis, through serological and molecular tools. Target tissues (skin, spleen, lymph nodes) collected from 71 European rabbits, 2 European hares, 7 red foxes, 11 European wildcats and 1 pine marten, were qPCR analysed for the detection of L. infantum DNA. Additionally, 40 rabbits, older than one year, were serologically screened for specific anti-Leishmania antibodies. Leishmania infantum was molecularly diagnosed in 5.4% (n = 5) of the examined animals (3/71 European rabbits, 2/7 red foxes). In many of the qPCR positive animals (4/5), the parasite DNA was more prevalent in visceral than cutaneous tissues. None of the positive animal showed signs of disease and/or macroscopic alterations of organs; low parasitic burden in all positive tissue samples was also recorded. Only one rabbit serum (i.e., 2.5%) tested positive for anti-Leishmania antibodies. The seropositive rabbit was in good health status and no amastigotes were observed in lymph-node aspirate and blood smears.This study provides first evidence of L. infantum infection in wild animals from Sicily (southern Italy). Despite the low prevalence of infection here reported, the circulation of the Leishmania in wild reservoirs in Sicily remains worthy of future investigations for a better understanding of their role in the epidemiology of the disease as well as to fine-tune control strategies in the area.     

Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at ?24, ?16, and ?0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non‐compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half‐life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day^?1 ml^?1), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.