Kinetic disposition, systemic bioavailability and tissue distribution of apramycin in broiler chickens

Apramycin was administered to chickens orally, intramuscularly and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. Single doses of apramycin at the rate of 75 mg kg⁻¹ body weight were given to broiler chickens by intracrop, i.m. and i.v. routes. The highest serum concentrations of apramycin were reached 0·20 and 0·76 hours after the oral and i.m. doses with an absorption half-life () of 0·10 and 0·19 hours and an elimination half life () of 1·22 and 2·31 hours respectively. The systemic bioavailability was 2·0 and 58 per cent after intracrop and i.m. administration, respectively, indicating poor absorption of the drug when given orally.Following i.v. injection, the kinetics of apramycin was described by a two-compartment open model with a () of 1·5 hours, () of 2·1 hours, V_d(ss) (volume of distribution) of 4·82 litre kg⁻¹ and C1_(B) (total body clearance) of 1·88 litre kg⁻¹ hour⁻¹. The serum protein-binding of apramycin was 26 per cent.The highest tissue concentrations of apramycin were present in the kidneys and liver. No apramycin residues were detected in tissues after six hours except in the liver and kidneys following intracrop dosing and kidneys following i.m. administration.     

Estimating relative risk of disease from outputs of logistic regression when the disease is not rare

Many epidemiologic studies in the veterinary field aim to quantify the relationships between risk factors and the occurrence of diseases. The strength of the association between a factor and a disease can be measured by (i) a relative risk (RR), or (ii) an odds ratio (OR) which is widely used because it is directly derived from the estimates of logistic regression. RR directly provides the relative increase in the probability of disease occurrence in case of exposure. OR is often interpretated as a multiplicative factor of the risk of disease occurrence when exposed, although it is not a good approximation of RR when the disease is not rare. The objective of this paper is to propose a method to estimate RR of disease from adjusted odds ratios derived from logistic regression when the disease is not rare.The method of estimation is developed for three different cases: (i) the factor and the outcome are dichotomous; (ii) the factor has more than two classes, and the outcome is dichotomous; and (iii) the factor and the outcome both have more than two classes. In all cases, the principles of estimation are the same: in a subpopulation including individuals diseased at level j (D_j) and not diseased (D₀), when exposed to level i (F_i) or not exposed to the factor (F₀), can be calculated with adjusted , and the frequencies of individuals exposed to level i (n_i&;j), of those not exposed (n_0&;j) and of those diseased (n_i&;j) among the individuals exposed to level i and not exposed. is the positive solution of the formula:

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A comparative study between mature ostriches (Struthio camelus) and adult cockerels with respect to true and apparent metabolisable energy values for maize,barley, oats and triticale

1. In three successive trials with cockerels and mature ostrich males the apparent and true metabolisable energy values, corrected for nitrogen retention (AME_n and TME_n) were determined by a balance method for malting barley, oats, triticale and yellow maize. All these ingredients were used as sole dietary components with the exception of triticale for ostriches which was diluted with 440 g/kg lucerne meal. The balance trial lasted for 5 d after an adaption period of 7 d for ostriches, and 3 d after an adaption period of one day for cockerels.

2. AME_n values for cockerels of malting barley, oats, triticale and maize were 11.6, 10.48, 11.44 and 14.42 MJ/kg respectively. Significantly higher values of 14.21, 12.65, 12.60 and 14.89 MJ/kg were determined for malting barley, oats, triticale and maize for ostriches.

3. TME_n values determined by regression yielded values in ostriches of 13.92, 12.27, 13.21 and 15.22 MJ/kg for malting barley, oats, triticale and maize respectively. The corresponding TME_n values in cockerels were 11.33, 10.63, 11.82 and 14.07 MJ/kg.

4. The ostrich is capable of utilising fibre more efficiently than poultry. The higher energy values observed for the various ingredients also indicated that the non‐starch polysaccharides such as ß‐glucans and arabinoxylans in the more fibrous energy sources had little if any effect on the available energy of these ingredients as found with poultry.

5. The potential of ostriches to utilise the more fibrous energy sources like barley, oats and triticale allows for their economical use in diet formulation. This possibility may result in markedly lower food costs for ostriches.     

Blood buffering in sedentary miniature horses after administration of sodium bicarbonate in single doses of varying amounts

Blood acid-base and electrolyte status was studied in four sedentary Miniature Horses treated with 200, 300, 400 and 500 mg of sodium bicarbonate (NaHCO₃) per kg of body weight (BW). Arterial blood was collected before treatment with NaHC0₃ and each hour for 5 h after treatment. All treatments resulted in an increase in blood pH, bicarbonate (HCO₃⁻) concentration and base excess (BE) by 1 h post-dosage, which continued through the 5th hour (P < .05). Treatment with 200 mg NaHC0₃/kg BW resulted in less elevated blood HCO₃⁻ concentrations (P < .03) and BE values (P < .01) when compared to the other treatments. Following dosing with NaHCO₃, plasma Na⁺ concentrations increased among all treatments but declined to initial values by 3 h post-treatment. The 200 mg NaHCO₃/kg BW dosage resulted in the smallest increases in plasma Na⁺ concentrations (P < .03). Both plasma K⁺ and Ca⁺⁺ concentrations were lower (P < .05) among all treatment groups 1 h post-dosage but returned to initial values by 5 h and 3 h posttreatment, respectively, with no differences (P >.05) among treatments. All NaHCO₃ dosages increased blood buffering capacity as indicated by increased blood pH, HCO₃⁻ concentration and BE. Maximum blood pH, HCO⁻₃ concentration and BE was reached using a dosage of 300 mg NaHCO₃/kg BW. Also, all treatments altered the plasma electrolyte concentrations.     

A comparative study between mature ostriches (Struthio camelus) and adult cockerels with regard to the true and apparent digestibilities of amino acids

1. A study was conducted to compare apparent and true digestibility of amino acids in a high protein experimental diet between young ostriches (7 months of age) and cockerels.

2. A mean value for true digestibility of amino acids (TAAD) of 0.837 ± 0.0073 (range 0.780 to 0.862) was derived for ostriches, compared with a mean value of 0.795 ± 0.0258 (range 0.723 to 0.825) for cockerels.

3. True retention of dietary protein was 0.646 ±0.0114 and 0.609 ±0.0643 for ostriches and cockerels respectively.

4. Results in the present study produced evidence that the method for determining metabolisable energy values of ingredients for ostriches is also suitable for measuring the digestibility of amino acids.

5. It was concluded that accurate diet formulation for ostriches requires the assessment of amino acid digestibilities for individual ingredients, because values derived from poultry would underestimate digestibilities for ostriches.     

Pharmacokinetic and pharmacodynamic interactions of tolfenamic acid and marbofloxacin in goats

Pharmacokinetic and pharmacodynamic properties in goats of the non-steroidal anti-inflammatory drug tolfenamic acid (TA), administered both alone and in combination with the fluoroquinolone marbofloxacin (MB), were established in a tissue cage model of acute inflammation. Both drugs were injected intramuscularly at a dose rate of 2 mg kg⁻¹. After administration of TA alone and TA + MB pharmacokinetic parameters of TA (mean values) were C_max = 1.635 and 1.125 μg ml⁻¹, AUC = 6.451 and 3.967 μg h ml⁻¹, t_1/2K₁₀ = 2.618 and 2.291 h, Vdarea/F = 1.390 and 1.725 L kg⁻¹, and ClB/F = 0.386 and 0.552 L kg⁻¹ h⁻¹, respectively. These differences were not statistically significant. Tolfenamic acid inhibited prostaglandin (PG)E₂ synthesis in vivo in inflammatory exudate by 53-86% for up to 48 h after both TA treatments. Inhibition of synthesis of serum thromboxane (Tx)B₂ ex vivo ranged from 16% to 66% up to 12 h after both TA and TA + MB, with no significant differences between the two treatments.From the pharmacokinetic and eicosanoid inhibition data for TA, pharmacodynamic parameters after dosing with TA alone for serum TxB₂ and exudate PGE₂ expressing efficacy (E_max = 69.4 and 89.7%), potency (IC₅₀ = 0.717 and 0.073 μg ml⁻¹), sensitivity (N = 3.413 and 1.180) and equilibration time (t_1/2K_e0 = 0.702 and 16.52 h), respectively, were determined by PK-PD modeling using an effect compartment model. In this model TA was a preferential inhibitor of COX-2 (COX-1:COX-2 IC₅₀ ratio = 12:1). Tolfenamic acid, both alone and co-administered with MB, did not affect leucocyte numbers in exudate, transudate or blood. Compared to placebo significant attenuation of skin temperature rise over inflamed tissue cages was obtained after administration of TA and TA + MB with no significant differences between the two treatments. Marbofloxacin alone did not significantly affect serum TxB₂ and exudate PGE₂ concentrations or rise in skin temperature over exudate tissue cages. These data provide a basis for the rational use of TA in combination with MB in goat medicine.     

Pharmacokinetics and bioavailability of moxifloxacin in buffalo calves

The pharmacokinetics of moxifloxacin were investigated in buffalo calves following a single intravenous and intramuscular administration of moxifloxacin (5 mg kg⁻¹ body wt.). Moxifloxacin concentrations in plasma and urine were determined by microbiological assay. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by a two compartment open model, whereas intramuscular administration data were best described by a one compartment open model. Following intravenous administration, the elimination half life (t_1/2β), volume of distribution (Vd_(area)) and total body clearance were 2.69 ± 0.14 h, 1.43 ± 0.08 L kg⁻¹ and 371.2 ± 11.2 ml kg⁻¹ h⁻¹, respectively. Following intramuscular administration, the absorption half life (t_1/2ka) was 0.83 ± 0.20 h. The systemic bioavailability (F) of moxifloxacin in buffalo calves was 80.0 ± 4.08%. Urinary excretion of moxifloxacin was less than 14% after 24 h of administration of drug. In vitro binding of moxifloxacin to plasma proteins of buffalo calves was 28.4 ± 3.77%. From the data of surrogate markers (AUC/MIC, C_max/MIC), it was determined in the buffalo calves that when administered by intravenous or intramuscular route at 5 mg kg⁻¹, moxifloxacin is likely to be effective against bacterial isolates with MIC ? 0.1 μg ml⁻¹.     

A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs

The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n = 6, (2.0 mg kg⁻¹), hydromorphone, n = 6, (0.2 mg kg⁻¹) or a placebo of blank liposomes, n = 3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in P_aCO₂, P_aO₂, (HCO₃-), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in P_aCO₂ (maximum (mean + SD] 44.4 + 1.1 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 82.4 + 4.7 mm of Hg) and pH (minimum (mean + SD) 7.31 + 0.01) compared with baseline. Administration of LEH resulted in significant increases in P_aCO₂ (maximum (mean + SD) 44.6 + 0.9 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 84.8 + 2.6 mm of Hg) and pH (minimum (mean + SD) 7.34 + 0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in P_aCO₂, P_aO₂, and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.     

Variability in tumor necrosis factor-α, nitric oxide,and xanthine oxidase responses to endotoxin challenge in heifers: Effect of estrous cycle stage

The severity of host response to some disease agents differs between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. Our objective was to determine in heifers whether the phase of estrous cycle affected immune response mediators after endotoxin challenge (LPS, 2.5 μg/kg BW, i.v.). Sixteen beef heifers (426 ± 9 kg) were reproductively synchronized with the two-injection protocol of dinoprost tromethamine (Lutalyse^®, Pfizer) to establish diestrus and estrus stages of the estrous cycle. Heifers were challenged with LPS on day 3 (E, estrus; n = 8) or day 10 (D, diestrus, n = 8) after the last i.m. injection of Lutalyse^®. In all heifers, plasma concentrations of tumor necrosis factor-α (TNF-α) peaked 2 h after LPS treatment (P < 0.01) and returned to basal level by 7 h. However, the integrated TNF-α response (area under the time × concentration curve, AUC) was greater in E than in D (P < 0.05). Plasma concentrations of nitrate + nitrite (NO_x, an estimate of NO production) increased (P < 0.01) in all heifers at 7 and 24 h after LPS; plasma NO_x AUC after LPS was greater in E than D (P < 0.01). Plasma xanthine oxidase activity (XO, a mediator of superoxide production) responses were also greater in E than D (P < 0.05). A companion LPS challenge study in steers validated that the protocol for and use of Lutalyse^® did not affect any of the immune parameters studied in heifers in response to LPS. Results indicate that the underlying physiological attributes of the estrus and diestrus phases of the estrous cycle constitute a major source of variability in the magnitude of proinflammatory response to bacterial toxins like LPS.     

Quantitative Accuracy of the Simplified Strong Ion Equation to Predict Serum pH in Dogs

Background

Electrochemical approach to the assessment of acid‐base states should provide a better mechanistic explanation of the metabolic component than methods that consider only pH and carbon dioxide.

Hypothesis/Objectives

Simplified strong ion equation (SSIE), using published dog‐specific values, would predict the measured serum pH of diseased dogs.

Animals

Ten dogs, hospitalized for various reasons.

Methods

Prospective study of a convenience sample of a consecutive series of dogs admitted to the Massey University Veterinary Teaching Hospital (MUVTH), from which serum biochemistry and blood gas analyses were performed at the same time. Serum pH was calculated (Hcal+) using the SSIE, and published values for the concentration and dissociation constant for the nonvolatile weak acids (A_tot and K _a), and subsequently Hcal+ was compared with the dog''s actual pH (Hmeasured+). To determine the source of discordance between Hcal+ and Hmeasured+, the calculations were repeated using a series of substituted values for A_tot and K _a.

Results

The Hcal+ did not approximate the Hmeasured+ for any dog (P = 0.499, r ² = 0.068), and was consistently more basic. Substituted values A_tot and K _a did not significantly improve the accuracy (r ² = 0.169 to <0.001). Substituting the effective SID (Atot−[HCO3−]) produced a strong association between Hcal+ and Hmeasured+ (r ² = 0.977).

Conclusions and clinical importance

Using the simplified strong ion equation and the published values for A_tot and K _a does not appear to provide a quantitative explanation for the acid‐base status of dogs. Efficacy of substituting the effective SID in the simplified strong ion equation suggests the error lies in calculating the SID.     

Plasma viscosity values and the relationship with age and sex in normal commercial broiler and layer strains of chickens

1. The plasma viscosity values of normal commercial broiler and layer strains of chicken were measured in relation to age and sex.

2. In both broilers and layers plasma viscosity values decreased at 2 weeks of age; probably reflecting the period of change from maternal plasma protein to the bird's self‐synthesised proteins.

3. There was a progressive rise in plasma viscosity in both strains and sexes with age. The increase was greatest in female layers at 17 weeks of age before lay.

4. There was no overall significant difference in viscosity values between fresh and frozen‐stored plasma samples.     

Evaluation of the Total Carbon Dioxide Apparatus and pH Meter for the Determination of Acid-Base Status in Diarrheic and Healthy Calves

Three simple tests of acid-base status were evaluated for field use. Blood samples were collected from 20 diarrheic and 24 healthy calves less than six weeks of age. One sample was collected anaerobically and immediately analyzed on a blood gas analyzer. The other samples were used for measurement of blood and serum pH using a pH meter and pH paper, and for serum total carbon dioxide (TCO₂) using a TCO₂ apparatus. The TCO₂ apparatus gave the best results and would be useful in the field. TCO₂ apparatus measurements had a high correlation, r=0.91, with blood gas analyzer blood bicarbonate values. Healthy calves have a serum TCO₂ content of 30 mmol/L and bicarbonate requirements for correcting metabolic acidosis in diarrheic calves can be calculated:

Bicarbonate required (mmol) = (30-TCO₂) × Body Weight × 0.6 This can be converted to grams of sodium bicarbonate by dividing by 12.

     

Pharmacokinetics of florfenicol after intravenous and intramuscular administration in New Zealand White rabbits

The pharmacokinetic disposition and bioavailability of florfenicol (FF) were determined after single intravenous (i.v.) and intramuscular (i.m.) administrations of 25 mg/kg b.w. to ten healthy New Zealand White rabbits. Plasma FF concentrations were determined by high-performance liquid chromatography (HPLC). The plasma pharmacokinetic values for FF were best described by a one-compartment open model. The elimination half-life (t_1/2β) was different (p < 0.05) however, the area under curve (AUC) was similar (p > 0.05) after i.v. and i.m. administrations. FF was rapidly eliminated (t_1/2β 1.49 ± 0.23 h), slowly absorbed and high (F, 88.75 ± 0.22%) after i.m. injection. In addition, FF was widely distributed to the body tissues (V_ss 0.98 ± 0.05 L/kg) after i.v. injection. In this study the time that plasma concentration exceeded the concentration of 2 μg/mL was approximately 6 h. For bacteria with MIC of 2 μg/mL, frequent administration at this dose would be needed to maintain the concentration above the MIC. However, it is possible that rabbit pathogens may have MIC values less than 2 μg/mL which would allow for less frequent administration. Further studies are necessary to identify the range of MIC values for rabbit pathogens and to identify the most appropriate PK-PD parameter needed to predict an effective dose.     

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.     

The role of backyard poultry flocks in the epidemic of highly pathogenic avian influenza virus (H7N7) in the Netherlands in 2003

In recent years, outbreaks of highly pathogenic avian influenza (HPAI) viruses have caused the death of millions of poultry and of more than 200 humans worldwide. A proper understanding of the transmission dynamics and risk factors for epidemic spread of these viruses is key to devising effective control strategies. The aim of this study was to quantify the epidemiological contributions of backyard flocks using data from the H7N7 HPAI epidemic in the Netherlands in 2003. A dataset was constructed in which flocks in the affected area were classified as susceptible (S), infected but not yet infectious (E), infectious (I), and removed (R). The analyses were based on a two-type SEIR epidemic model, with the two types representing commercial poultry farms and backyard poultry flocks. The analyses were aimed at estimation of the susceptibility (g) and infectiousness (f) of backyard flocks relative to commercial farms. The results show that backyard flocks were considerably less susceptible to infection than commercial farms (), while estimates of the relative infectiousness of backyard flocks varied widely (). Our results indicate that, from an epidemiological perspective, backyard flocks played a marginal role in the outbreak of highly pathogenic avian influenza in the Netherlands in 2003.     

Haematology and blood composition at two ambient temperatures in genetically fat and lean adult broiler breeder females fed ad libitum or restricted throughout life

1. Genetically fat and lean adult broiler breeder females were fed ad libitum or restricted throughout life. At one year of age, comparisons of blood viscosity and haematology and changes in blood chemistry after exposure to thermal stress were conducted.

2. Whole blood viscosity was more than twice as high, and plasma triglyc‐eride and haemoglobin concentrations were over 30% higher in fat line than in lean line females fed ad libitum or in restricted birds of both genotypes.

3. Mean cell haemoglobin concentration was higher and mean cell volume lower in fat compared with lean line females.

4. Food restriction was associated with lower plasma triglyceride concentrations, lower numbers of heterophils and monocytes and a lower heterophil‐lymphocyte ratio.

5. Fat line birds had a higher blood pCO₂ and lower pH than lean line birds.

6. Thermal stress was associated in ad libitum‐fed birds with a rise in blood pH and a decrease in pCO₂, and in restricted birds with a decline in blood pH and an increase in pCO₂.

7. Blood creatine kinase activity increased in all groups under thermal stress.     

Effects of dietary copper supplementation on production performance and plasma biochemical parameters in broiler chickens

1. A study was conducted to estimate the effect of copper (Cu) supplementation on growth performance and biochemical profiles of blood and meat in broiler chickens.

2. A total of 240?d-old broiler chicks (Vencobb-100) were randomly divided into 12 groups, each of 20 chicks (4 treatments?×?3 replicates).

3. The basal diet (T₁) contained 215?g?kg^?1 crude protein (CP), 12·76?MJ?kg^?1 ME, 32?g?kg^?1 total calcium and 5?g?kg^?1 total phosphorus. T_2, T₃ and T₄ were formulated to contain an additional 75, 150 and 250?mg?Cu?kg^?1 diet, respectively. Copper sulphate pentahydrate (CuSO₄, 5H₂O) was used as the source of Cu.

4. Significant reductions in plasma total cholesterol and triglyceride, and an elevated concentration of HDL-cholesterol, were observed in the chickens fed with 250?mg?Cu?kg^?1 (T₄) of feed at the 3rd and 6th week of the experiment. Total cholesterol in meat decreased significantly in the birds fed with dietary Cu at 250?mg?kg^?1 (T₄) of feed.

5. Growth performance was measured in terms of live weight gain, cumulative feed intake and feed conversion ratio at the end of d 21 and d 42 of the experiment, and the result was found to be commercially beneficial for the chickens receiving 150?mg?Cu?kg^?1 (T₃) of diet. The concentration of Cu in breast muscle and liver increased significantly at the end of experiment.

6. From this study it can be concluded that supplementation with dietary Cu may be beneficial for production performance and plasma biochemical characteristics of broiler chickens.     

PK-PD integration and modeling of marbofloxacin in sheep

The fluoroquinolone antimicrobial drug, marbofloxacin, was administered intravenously (IV) and intramuscularly (IM) to sheep at a dose rate of 2 mg kg⁻¹ in a 2-period cross-over study. Using a tissue cage model of inflammation, the pharmacokinetic properties of marbofloxacin were established for serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). For serum, after IV dosing, mean values for pharmacokinetic parameters were: clearance 0.48 L kg⁻¹ h⁻¹; elimination half-life 3.96 h and volumes of distribution 2.77 and 1.96 L kg⁻¹, respectively, for V_darea and V_ss. After IM dosing mean values for pharmacokinetic variables were: absorption half-time 0.112 h, time of maximum concentration 0.57 h, terminal half-life (T½el) 3.65 h and bioavailability 106%. For exudate, mean T½el values were 12.38 and 13.25 h, respectively, after IV and IM dosing and for transudate means were 13.39 h (IV) and 12.55 h (IM).The in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and ex vivo time-kill curves for marbofloxacin in serum, exudate and transudate were established against a pathogenic strain of Mannheimia haemolytica. Integration of in vivo pharmacokinetic data with MIC determined in vitro provided mean values of area under curve (AUC)/MIC ratio for serum, exudate and transudate of 120.2, 156.0 and 156.6 h after IV dosing and 135.5, 165.3 and 146.2 h after IM dosing, respectively. After IM administration maximum concentration (C_max)/MIC ratios were 21.1, 6.76 and 5.91, respectively, for serum, exudate and transudate. The ex vivo growth inhibition data after IM administration were fitted to the sigmoid E_max (Hill) equation to provide values for serum of AUC_24 h/MIC producing, bactericidal activity (22.51 h) and virtual eradication of bacteria (35.31 h). It is proposed that these findings might be used with MIC₅₀ or MIC₉₀ data to provide a rational approach to the design of dosage schedules which optimise efficacy in respect of bacteriological as well as clinical cures.     

Environmental Exposures and Airway Inflammation in Young Thoroughbred Horses

Background

Inflammatory airway disease (IAD) in horses is a widespread, performance‐limiting syndrome believed to develop in response to inhaled irritants in the barn environment.

Objectives

To evaluate changes in bronchoalveolar lavage fluid (BALF) cytology and exposure to particulates, endotoxin, and ammonia during horses'' first month in training.

Animals

Forty‐nine client‐owned 12‐ to 36‐month‐old Thoroughbred horses entering race training.

Methods

In this prospective cohort study, a convenience sample of horses was assigned to be fed hay from a net (n = 16), whereas the remaining horses were fed hay from the ground (n = 33). BALF was collected at enrollment and after 14 and 28 days in training. Respirable particulate, inhalable particulate, respirable endotoxin, and ammonia concentrations were measured at the breathing zone of each horse weekly.

Results

Median respirable particulates were significantly higher when horses were fed from hay nets than when fed hay from the ground (hay net 0.28 mg/m³, no hay net 0.055 mg/m³, P < .001). Likewise, inhalable particulate (hay net 8.3 mg/m³, no hay net 3.3 mg/m³, P = .0064) and respirable endotoxin (hay net 173.4 EU/m³, no hay net 59.2 EU/m³, P = .018) exposures were significantly higher when horses were fed from hay nets. Feeding hay from a net resulted in significantly higher BALF eosinophil proportions over time (P < .001). BALF eosinophils were significantly related to respirable particulate exposure (14 days in training r _s = 0.37, P = .012, 28 days in training, r _s = 0.38, P = .017).

Conclusions and Clinical Importance

Pulmonary eosinophilic inflammation develops in response to respirable particulate exposure in young Thoroughbreds, indicating a potential hypersensitivity to inhaled particulate allergens.