Assessing the role of polyethylene microplastics as a vector for organic pollutants in soil: Ecotoxicological and molecular approaches.

Microplastics (MPs), pharmaceuticals and pesticides are emerging pollutants with proposed negative impacts on the environment. Rising interest in investigations of MPs is likely related to their potential to accumulate in agricultural systems as the base of the food chain. We applied an integrated approach using classic bioassays and molecular methods to evaluate the impact associated with a mixture of three types of polyethylene (PE) microbeads, namely, white (W), blue (B), and fluorescent blue (FB), and their interactions with pollutants (OCs), including ibuprofen (IB), sertraline (STR), amoxicillin (AMX) and simazine (SZ), on different soil organisms. PE-MPs exhibited different abilities for the adsorption of each OC; W selectively adsorbed higher amounts of SZ, whereas B and FB preferably retained AMX. Standard soil was artificially contaminated with OCs and MPs (alone or combined with OCs) and incubated for 30 days. The presence of MPs or MPs and OCs (MIX) in soil did not produce any effect on Caenorhabditis elegans endpoint growth, reproduction, or survival. Inhibition of leaf growth in Zea mays was detected, but this negative effect declined over time, while the inhibition of root growth increased, especially when OCs (32%) or MIX (47%) were added. Moreover, the expression of the antioxidant genes CAT 1, SOD-1A and GST 1 on plants was affected by the treatments studied. The addition of MPs or MIX significantly affected the soil bacterial phylogenetic profile, which selectively enriched members of the bacterial community (particularly Proteobacteria). The predicted functional profiles of MP/MIX samples indicated a potential impact on the carbon and nitrogen cycle within the soil environment. Our results indicate that MPs and their capability to act as pollutant carriers affect soil biota; further studies should be carried out on the bioavailability of OCs adsorbed by microplastics and how long it takes to leach these OCs into different organisms and/or ecosystems.

Pharmacokinetic Behaviour of Enrofloxacin after Single Intramuscular Dosage in American Black Vultures (Coragyps atratus).

The aim of the study was to investigate the intramuscular pharmacokinetics of enrofloxacin in black vultures (Coragyps atratus). The pharmacokinetics of a single intramuscular dose (10 mg/kg) of enrofloxacin was studied in six vultures. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high-performance liquid chromatography (HPLCuv). Pharmacokinetic parameters were estimated using non-compartmental and compartmental analysis. After intramuscular administration, enrofloxacin showed a rapid and complete absorption, reaching a Cmax value of 3.26 ± 0.23 µg/mL at 1.75 ± 0.53 h. A long terminal half-life of 19.58 h has been observed. Using previously published MIC values to perform a PK/PD analysis, cumulative fraction responses obtained after Monte Carlo simulation for AUC/MIC > 30, 50 and 125 were 72.93%, 72.34% and 30.86% for E. coli and 89.29%, 88.89% and 58.57% for Mycoplasma synoviae, respectively. Cumulative fraction responses obtained for Cmax/MIC index were 33.93% and 40.18% for E. coli and M. synoviae, respectively. The intramuscular administration of 10 mg/kg could be appropriate to treat infectious diseases caused by gram-positive bacteria with MIC value lower than 1 µg/mL; however, although enrofloxacin showed a slow elimination in black vultures, plasma concentrations were insufficient to reach the gram-negative stablished breakpoints.

Antimicrobial resistance in Galapagos tortoises as an indicator of the growing human footprint.

Antimicrobial resistance has become one of the main public health threats worldwide with anthropogenic activities driving the spread of resistance. Understanding and combatting the spread of resistant bacteria is a top priority for global health institutions, and it is included as one of the main goals of the One Health initiative. Giant tortoises (Chelonoidis spp.), some of the most iconic species on Earth, are widely distributed across the Galapagos archipelago and are thus perfect candidates to test the hypothesis that wildlife species in the Galapagos carry antimicrobial resistant genes (ARGs) associated with human activities. We sampled a total of 200 free-living Galapagos tortoises from western Santa Cruz Island (C. porteri), the most human-populated island of the archipelago, and 70 tortoises (C. vandenburghi) from the isolated Alcedo Volcano on Isabela Island, a natural area with minimal human presence. Fecal samples were analyzed by quantitative PCR for a panel of 21 ARGs conferring resistance for eight antimicrobial classes. We found ARGs in both Santa Cruz and Alcedo Volcano giant tortoises; however, both qualitative and quantitative results showed higher loads of ARGs in tortoises inhabiting the human modified environments of Santa Cruz. Moreover, Santa Cruz tortoises sampled in higher human-modified landscapes (i.e., farmlands and urban areas) presented a higher number of ARGs, antimicrobial classes, and multi-resistant microbiomes than those from less anthropized areas within the same island. Our findings suggest that human activities in Galapagos have a negative impact on ecosystem health through ARG dispersal. This research highlights a new threat for the health and conservation of the unique wildlife of the Galapagos, their ecosystems, and the humans inhabiting this World Heritage Site. Our recommendation to local policy makers is to control and reduce the use of antibiotics in both human and animal health, thus helping enforce antimicrobial regulations.

Effect of chemically modified tetracycline-8 (CMT-8) on hematology, blood chemistry, cytokines and peripheral blood lymphocyte subsets of healthy dogs.

Tetracyclines are antibiotics widely used in human and veterinary medicine. Effects on the immune system and inflammatory response, including effects on blood leukocytes proliferation and function and in cytokines synthesis, have been described. Chemically modified tetracyclines (CMT) have lost their antimicrobial activity, but maintain these other properties. This study analyzes the effect of chemically modified tetracycline-8 (CMT-8) on the evolution of complete blood count, blood chemistry, the mRNA expression of selected cytokines and peripheral blood lymphocyte subpopulations distribution in healthy dogs. CMT-8 at a dose of 10 mg/kg once daily was administered per os to six healthy dogs. A control group of five healthy dogs, living in the same conditions than dogs treated with CMT-8, received placebo with an identical therapeutic regimen. When given at the doses used in this study, no side effects of CMT-8 were detected, suggesting a good tolerance and a limited toxicity of the drug. Dogs treated with CMT-8 showed a gradual increase in mean corpuscular hemoglobin. The administration of CMT-8 in healthy dogs did not affect blood mRNA expression of IFN-γ, TNFα, IL-4, IL-6, IL-10, IL-12 p40 and IL-13. However, the lymphocytes expressing class II MHC on their surface decreased during the first two weeks of CMT-8 treatment and subsequently increased for the next three months. Considering the absence of antimicrobial properties of the drug, the effects of CMT-8 detected in this study seem to be unrelated to the classical antimicrobial activity attributed to tetracyclines.

Agreement between noninvasive oscillometric and invasive blood pressure measurements in isoflurane-anesthetized guinea pigs (Cavia porcellus).

OBJECTIVE: To assess the agreement between an oscillometric device and invasive blood pressure (IBP) measurements in anesthetized healthy adult guinea pigs. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of eight adult Hartley guinea pigs. METHODS: All animals were anesthetized; a carotid artery was surgically exposed and catheterized for IBP measurements. A size 1 cuff placed on the right thoracic limb was connected to an oscillometric device for noninvasive blood pressure (NIBP) assessment. Concurrent pairs of systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures were recorded simultaneously with both methods every 3 minutes for 30 minutes. Agreement between IBP and NIBP measurements was determined using the Bland-Altman method, considering the recommended standards for the validation of NIBP measurement devices proposed by the American College of Veterinary Internal Medicine (ACVIM). RESULTS: The bias and the 95% limits of agreement were: -14 (-31 to 3) mmHg, -2 (-14 to 10) mmHg and -1 (-13 to 11) mmHg for SAP, DAP and MAP, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The oscillometric device used in this study to measure NIBP did not meet ACVIM criteria for validation. It showed good agreement for DAP and MAP but not for SAP measurements. Considering the small size of these animals and the resulting difficulty in performing percutaneous arterial catheterization, this device might be a useful tool to assess MAP and DAP during anesthetic procedures in adult guinea pigs.

Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs.

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p < 0.01) or rK39 (p < 0.01) as the target antigen. In addition, all dogs were classified as parasite negative based on Leishmania nested PCR and quantitative real time PCR tests and as well as an inability to culture of promastigote parasites from lymph nodes and bone marrow tissue samples taken at day 90 post-treatment. However, treatment did not cure the dogs as parasites were detected at 10 months post-treatment, indicating that a different dosing regimen is required to cause long term cure or prevent relapse.

Pharmacokinetics of doxycycline after oral administration of multiple doses in dogs.

The aim of this study was to determine the pharmacokinetic parameters of doxycycline in dogs and assess the efficacy of an oral drug dosage regimen of 10 mg/kg daily for 28 days through Pharmacokinetic/Pharmacodynamic (PK/PD) target analysis based on Monte Carlo simulation, using previously published data for the zoonotic pathogen Staphylococcus pseudintermedius. After a multiple-dosage regimen, the accumulation index was 1.88 ± 0.82. The Cmaxss and Cminss values were 5.18 ± 1.81 µg/ml and 1.91 ± 1.35 µg/ml, respectively. There were statistically significant differences for Cmax, Cmin at 24 hr, MRTt, AUCt and AUC∞ between days 1 and 28. The Cminss value was over the MIC of the principal pathogens, and Cmaxss was higher than the resistance values (>2 µg/ml). For AUC/MIC indices of 12, 25 and 40, the cumulative fraction responses (CFR) were 94.01%, 69.55% and 60.86%, respectively; for an MIC value of 2 µg/ml, the corresponding probability of target attainment (PTA) was 99.94%, 84.78% and 45.16%, respectively. Doxycycline was used against numerous localized infections in different organs and tissues. For the strains with MIC < 1 µg/mL, PTA was close to 100%, even for the most demanding ones, specifically 94.98% for an index of 40% and 99.9% for an index of 25.

Pododermatitis in raptors admitted in a wildlife rehabilitation centre in central spain.

Pododermatitis is a chronic and progressive bacterial infectious disease of birds´ footpads, especially associated with captivity, which could represent an important problem in wildlife rehabilitation centres, delaying the release of the birds to the environment and harming their conservation. The objectives of the present study were i) to estimate the incidence rate of pododermatitis, ii) to analyse the influence of environmental, physiological, and pathological factors which may influence the onset of the infection in raptors after their admission to a rehabilitation centre, and iii) to follow up the evolution and macroscopic characteristics of the lesion. An observational retrospective study was carried out on clinical cases of raptors (n = 2004) admitted in a rehabilitation centre in central Spain from 2009 to 2015. The proportion of pododermatitis was 6.9%, with an incidence density of 6.8 cases/100 bird-years at risk. Our results showed that the disease was more likely to occur in birds staying longer (P < 0.001). According to Cox analysis, the variables 'raptor family' (P < 0.001) and 'age' (P = 0.002) may have significant effects on pododermatitis development. Raptors from the Falconidae and Strigidae families were less likely to develop pododermatitis than those from the Accipitridae family, with a hazard ratio (HR) of 0.31 and 0.13, respectively. Regarding age, fully feathered raptors had a three-fold higher risk of having pododermatitis than non-fully feathered birds. Survival analysis of time of pododermatitis development revealed significant differences associated with the variables 'raptor family' (P < 0.03); 'age' (P < 0.001) and 'cause of admission' (P = 0.001). Duration of the pathology (P < 0.05) and lesion location (P < 0.001) seemed to be phylogenetic dependent. Injuries were primarily located in the toes area or the whole footpad of birds belonging to the Accipitridae or Falconidae families, respectively (P = 0.003).

Evaluation of allometric scaling as a tool for extrapolation of the enrofloxacin dose in American black vultures (Coragyps atratus).

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species. ANIMALS: 6 healthy adult American black vultures. PROCEDURES: Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed. RESULTS: Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Levels of blood lead in Griffon vultures from a Wildlife Rehabilitation Center in Spain.

Lead is considered a highly toxic contaminant with important impacts to bird wildlife. Griffon vultures (Gyps fulvus) are a sensitive indicator of the level of environmental contamination due to their position at the top of the food chain and their dependence on human activities. The aim of this study was to assess susceptibility to lead intoxication in Griffon vultures admitted to Wildlife Rehabilitation Centers (WRC), measuring blood lead levels and determining if blood lead concentrations are related to clinical signs, hematological, biochemical or radiographic findings. Also, the influence of age, gender, body condition, season and primary cause of admission were evaluated. This study was realized in all Griffon vultures admitted during a period of one year in the Rehabilitation Center GREFA. Blood lead levels are measured by using anodic stripping voltammetry. In Griffon vultures, we observed that 26% of the analyzed birds presented lead levels above 20µg/dL with 74% below 20µg/dL ([Pb]<20 =9.34±5.60µg/dL). In our study, statistically significant differences were found for lead according to sex, season of admission to the center and body condition. A negative correlation was found between levels of metal and hematocrit. No association was found between clinical signs and blood lead levels in Griffon vultures, except for digestive signs as stasis and weight loss. On numerous occasions, the intoxication in this specie is related to ingestion of lead ammunition; however, we have not detected radiographic lead in our vultures. Compared with other studies, we generally found low levels of lead in blood of Griffon vultures but the blood of all birds admitted to WRC presented detectable lead concentrations. This species apparently presents a higher sensibility to the toxic effects of this metal than that described by other authors. It have been observed that there is some evidence that suggests that subclinical levels of lead could be related with a predisposition to injury or diseases, even though these birds might be admitted for other causes. The detection of levels of blood lead in animals that are admitted to a recovery center will give valuable information which could be used to monitor spatial and temporal variations and provide a clearer picture of temporal levels of this contaminant in this emblematic avian specie.

Pharmacokinetic behavior of enrofloxacin and its metabolite ciprofloxacin in urutu pit vipers (Bothrops alternatus) after intramuscular administration.

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 microg/ml. The long half-life during the terminal elimination phase (t1/2 lambda = 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 microg/ml at 13.45 hr, and the fraction of enrofloxacin metabolized to ciprofloxacin was 13.06%. If enrofloxacin's minimum inhibitory concentration (MIC90) values of 0.5 microg/ml were used, the ratios AUC(e+c): MIC90 (276 +/- 67 hr) and Cmax(e+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 < or = 0.5 microg/ml. For less susceptible bacteria, a dose increase and/or an interval reduction should be evaluated.

Pharmacokinetic and pharmacodynamic properties of enrofloxacin in southern crested caracaras (Caracara plancus).

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 x 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 microg x 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 (C(max)) was 3.92 microg/mL. Values of minimum inhibitory concentration (MIC), C(max), and AUC have been used to predict the clinical efficacy of a drug in treating bacterial infections, with a C(max)/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 microg/mL, values of C(max)/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 < or = 0.25 microg/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 < or = 0.25 microg/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.

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

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 microg/mL and 3.75 +/- 0.56 microg x 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 microg/mL or 0.2 microg/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 microg/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.

Disposition of marbofloxacin in vulture (Gyps fulvus) after intravenous administration of a single dose.

The pharmacokinetics properties of marbofloxacin were studied in adult Eurassian Griffon vulture after single-dose intravenous (IV) administration of 2mg/kg. Drug concentration in plasma was determined by high-performance liquid chromatography and the data obtained were subjected to compartmental and non-compartmental kinetic analysis. Marbofloxacin presented a volume of distribution at steady-state (Vdss) of 1.51±0.22L and total plasma clearance (Cl) of 0.109±0.023L/hkg. The permanence of this drug was long in vultures (T(1/2)(λ)=12.51±2.52h; MRT(∞)=13.54±2.29h). The optimal dose of marbofloxacin estimated is 2.73mg/kg per day for the treatment of infections in vultures with MIC(90)=0.2µg/mL.

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 micro 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 micro g x 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.

Effects of age on the pharmacokinetics of single dose sulfamethazine after intravenous administration in cattle.

Sulphonamides are still being used widely, influenced by the low cost and the efficacy against many common bacterial infections, since they present a broad spectrum of activity. The aim of this study was to determine the effect of age on the pharmacokinetic/pharmacodynamics (PK/PD) integration of intravenous sulfamethazine (60 mg/kgbw) in cattle, and the possible therapeutic outcomes. Six healthy female calves, at the age of one, three, seven and fifteen weeks were used. Normality analysis was assessed with the Shapiro-Wilk test. Non-parametric tests for paired data were used. Plasma concentrations were quantified using HPLC/uv. Differences were found between one-three-weeks-old calves and seven-fifteen-weeks-old calves, in pharmacokinetic parameters (clearance, area under the concentration-time curve and elimination half-life) and in the PK/PD integration. The ratios obtained in PK/PD integration (T>MIC, WAUC) confirm that it is necessary to apply twice the dose of sulfamethazine in > or = 7 weeks-old cattle to reach a satisfactory dosage regimen (MIC > or = 32 microg/mL).

Pharmacokinetics and pharmacodynamics of chlorpyrifos in male and female cattle after topical administration.

The aim of this work was to study the pharmacokinetic behaviour and the inhibitory effect on acetylcholinesterase and butyrylcholinesterase activities of chlorpyrifos in male and female cattle after pour-on administration. Determination of cholinesterase activity in plasma and erythrocyte was carried out according to Ellman kinetic method. The mean baseline activities were 9338.39 +/- 1331.61 and 13220.69 +/- 2274.18 to acetylcholinesterase and 624.65 +/- 39.32 and 641.68 +/- 88.08 IU/L to butyrylcholinesterase in females and males, respectively. Acetylcholinesterase was the predominant form of cholinesterase analyzed, with low levels of butyrylcholinesterase. The basal acetylcholinesterase activities of the bulls were significantly greater than those of cows. The inhibitory effect of topical chlorpyrifos administration was lower on butyrylcholinesterase than on acetylcholinesterase. Chlorpyrifos peak plasma concentration (male:10.920 +/- 4.18; female:12.12 +/- 3.88 microg/L) were reached at 11.92 +/- 9.19 and 8.17 +/- 7.67 h in male and female, respectively. The values of area under curve were 185.96 +/- 168.45 and 278.89 +/- 270.00 microg h/L and mean residence time were 13.95 +/- 8.10 and 14.90 +/- 9.80 h in male and female, respectively.

Pharmacokinetic behaviour of enrofloxacin in greater rheas following a single-dose intramuscular administration.

The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats.

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.

The pharmacokinetic behaviour of marbofloxacin in Eurasian buzzards (Buteo buteo) after intraosseous administration.

This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.