LOW PREVALENCE OF HAEMOSPORIDIANS IN BLOOD AND TISSUE SAMPLES FROM HUMMINGBIRDS.

Hummingbirds are vital members of terrestrial ecosystems, and because of their high metabolic requirements, they serve as indicators of ecosystem health. Monitoring the parasitic infections of hummingbirds is thus especially important. Haemosporidians, a widespread group of avian blood parasites, are known to infect hummingbirds, but little is known about the prevalence and diversity of these parasites in hummingbirds. The prevalence of haemosporidians in several hummingbird species was examined and we compared 4 different tissue types in detecting parasites by polymerase chain reaction (PCR). Blood samples from 339 individuals of 3 different hummingbird species were tested, and 4 individuals were found positive for haemosporidian infection, a prevalence of 1.2%. Hummingbird carcasses (n = 70) from 5 different hummingbird species were also sampled to assess differences in detection success of haemosporidians in heart, kidney, liver, and pectoral muscle tissue samples. Detection success was similar among tissue types, with haemosporidian prevalence of 9.96% in heart tissue, 9.52% in kidney tissue, 10.76% in liver tissue, and 11.76% in pectoral muscle tissue. All tissue samples positive for haemosporidian infection were from the Black-chinned Hummingbird (Archilochus alexandri). Possible reasons for low prevalence of these blood parasites could include low susceptibility to insect vectors or parasite incompatibility in these hummingbirds.

Detection and prevalence of Haemoproteus archilochus (Haemosporida, Haemoproteidae) in two species of California hummingbirds.

Haemosporidian blood parasites are transmitted to a wide range of avian hosts via blood-sucking dipteran vectors. Microscopy has revealed an impressive diversity of avian haemosporidia with more than 250 species described. Moreover, PCR and subsequent sequence analyses have suggested a much greater diversity of haemosporidia than morphological analyses alone. Given the importance of these parasites, very few studies have focused on the charismatic hummingbirds. To date, three Haemoproteus species (Haemoproteus archilochus, Haemoproteus trochili, and Haemoproteus witti) and one Leucocytozoon species (Leucocytozoon quynzae) have been described in blood samples taken from hummingbirds (Trochilidae). Unconfirmed Plasmodium lineages have also been detected in hummingbirds. Here, we report the detection of H. archilochus in two hummingbird species (Calypte anna and Archilochus alexandri) sampled in Northern California and perform a phylogenetic analysis of mitochondrial cytochrome b (cyt b) gene lineages. A total of 261 hummingbirds (157 C. anna, 104 A. alexandri) were sampled and screened for blood parasites using PCR and microscopy techniques. Combining both methods, 4 (2.55%) haemosporidian infections were detected in C. anna and 18 (17.31%) haemosporidian infections were detected in A. alexandri. Molecular analyses revealed four distinct H. archilocus cyt b lineages, which clustered as a monophyletic clade. No species of Plasmodium or Leucocytozoon were detected in this study, raising the possibility of specific vector associations with hummingbirds. These results provide resources for future studies of haemosporidian prevalence, diversity, and pathogenicity in California hummingbird populations.

Pharmacokinetic parameters for single- and multi-dose regimens for subcutaneous administration of a high-dose ceftiofur crystalline-free acid to neonatal foals.

The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 µg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 µg/mL and ≥2.0 µg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0→∝ ) was 246.2 ± 30.7 h × µg/mL and 172.7 ± 27.14 h × µg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.

Protocol for diversion of confirmed positive bulk raw milk tankers to calf ranches - A review of the Pharmacokinetics of tetracyclines and sulfonamides in veal calves.

The tetracyclines (TTC) and sulfonamides are among the most common residues found in bulk raw milk samples. Detection of drug residues in bulk milk (BM) tankers demonstrates that the product is not suitable for human consumption. Discarding BM with residue-contaminated milk is a waste of a valuable commodity, and a repurposing for consumption at calf ranches is a way to recapture some value. However, if calves consuming milk with drug residues are slaughtered for veal, their meat could contain drug residues. The objective of this review is to provide a residue avoidance strategy for TTC and sulfonamide residues in veal. To determine the pharmacokinetic properties of each drug a structured review of the literature was performed and the study inclusion criteria were that the publication used dairy breed calves, with body weight <330 kg or <6 months of age. The most pertinent parameters were determined to be plasma, tissue elimination half-lives, and systemic bioavailability. The results of this review were integrated with milk and tissue testing levels of quantification and tissue tolerances to formulate a recommended withdrawal interval for calves ingesting this milk. The suggested withdrawal interval of 20 days will ensure that no veal calves will test positive for residues from being fed this milk.

Pharmacokinetic indices for cefovecin after single-dose administration to adult sea otters (Enhydra lutris).

Seven sea otters received a single subcutaneous dose of cefovecin at 8 mg/kg body weight. Plasma samples were collected at predetermined time points and assayed for total cefovecin concentrations using ultra-performance liquid chromatography and tandem mass spectrometry. The mean (±SD) noncompartmental pharmacokinetic indices were as follows: CMax (obs) 70.6 ± 14.6 µg/mL, TMax (obs) 2.9 ± 1.5 h, elimination rate constant (kel ) 0.017 ± 0.002/h, elimination half-life (t1/2kel) 41.6 ± 4.7 h, area under the plasma concentration-vs.-time curve to last sample (AUClast) 3438.7 ± 437.7 h·µg/mL and AUC extrapolated to infinity (AUC0→∞ ) 3447.8 ± 439.0 h·µg/mL. The minimum inhibitory concentrations (MIC) for select isolates were determined and used to suggest possible dosing intervals of 10 days, 5 days, and 2.5 days for gram-positive, gram-negative, and Vibrio parahaemolyticus bacterial species, respectively. This study found a single subcutaneous dose of cefovecin sodium in sea otters to be clinically safe and a viable option for long-acting antimicrobial therapy.

Evaluation of an extended-release formulation of ceftiofur crystalline-free acid in koi (Cyprinus carpio).

The use of an extended release ceftiofur crystalline-free acid formulation (CCFA, Excede For Swine(®) , Pfizer Animal Health) in koi was evaluated after administration of single intramuscular (i.m.) or intracoelomic (i.c.) doses. Twenty koi were divided randomly into a control group and four treatment groups (20 mg/kg i.m., 60 mg/kg i.m., 30 mg/kg i.c., and 60 mg/kg i.c.). Serum ceftiofur-free acid equivalents (CFAE) concentrations were quantified. The pharmacokinetic data were analyzed using a nonlinear mixed-effects approach. Following a CCFA injection of 60 mg/kg i.m., time durations that serum CFAE concentrations were above the target concentration of 4 µg/mL ranged from 0.4 to 2.5 weeks in 3 of 4 fish, while serum CFAE concentrations remained below 4 µg/mL for lower doses evaluated. Substantial inter-individual variations and intra-individual fluctuations of CFAE concentrations were observed for all treatment groups. Histological findings following euthanasia included aseptic granulomatous reactions, but no systemic adverse effects were detected. Given the unpredictable time vs. CFAE concentration profiles for treated koi, the authors would not recommend this product for therapeutic use in koi at this time. Further research would be necessary to correlate serum and tissue concentrations and to better establish MIC data for Aeromonas spp. isolated from naturally infected koi.

Interspecies allometric meta-analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species.

Allometric scaling is widely used for the determination of first dosage regimen and the interpolation or extrapolation of pharmacokinetic parameters across many animal species during drug development. In this article, 85 drugs used in veterinary medicine obtained from the Food Animal Residue Avoidance Databank database were selected for allometric scaling analysis. Outlier species were identified by statistical methods. The results showed that 77% and 88% of drugs displayed significant correlations between total systemic clearance (CL) and volume of distribution at steady status (Vss) vs. body weight (P < 0.05) on a log-log scale, respectively. The distribution of the allometric exponent b for CL and Vss displays approximate normal distribution, with means (0.87 and 0.99) and standard deviations (0.143 and 0.157) for CL and Vss, respectively. Twelve drugs were identified to have at least one outlier species for CL and ten drugs for Vss. The human CL and Vss were predicted for selected drugs by the obtained allometric equations. The predicted CL and Vss were within a threefold error compared to observed values, except the predicted CL values for antipyrine, warfarin and diazepam. The results can be used to estimate cross-species pharmacokinetic profiles for predicting drug dosages in veterinary species, and to identify those species for which interpolation or extrapolation of pharmacokinetics properties may be problematic.

Safety of fenbendazole in Chinese ring-necked pheasants (Phasianus colchicus).

Ring-necked pheasants raised on propagation farms can be severely parasitized with Syngamus trachea (gapeworm) and other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic that is not currently approved for game bird species in the United States. The objective of this work was to provide target animal safety data to support a label claim for fenbendazole in pheasants at 100 parts per million (ppm) in the feed for 7 consecutive days. Demonstration of safety in young pheasants and a separate demonstration of reproductive safety in adult birds were required. In the young bird study, 160 Chinese ring-necked pheasants (Phasianus colchicus, 80 males and 80 females) were fed a commercial game bird starter ration containing no antibiotics, growth promoters, or coccidiostats until day 0 of the study (approximately 21 days of age). On day 0 the birds were placed on their respective study diets containing fenbendazole at 0, 100, 300, and 500 ppm for 21 days (three times the normal treatment duration). Clinical observations were recorded twice daily. Feed consumption, feed conversion rate, and body weights were determined for each pen. Three birds from each pen were randomly selected for necropsy, histopathology, and clinical pathology. Birds were carefully examined for feathering abnormalities immediately following euthanasia. The remaining birds in each pen were submitted for drug concentration analysis so that concentrations (for low vs. high treatment levels) could be correlated with clinical observations, clinical pathology, and histologic findings. There no morbidities or mortalities after study day--1. There were no statistically significant treatment-related differences in feed consumption, feed conversion rates, body weights, serum biochemistry profiles, hematologic profiles, gross necropsy findings, histopathologic examination, and feathering. Allowable liver and muscle concentrations of fenbendazole sulfone in turkeys are 6 and 2 ppm, respectively, with a 6-hr feed withdrawal. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young pheasants and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, two large game bird farms fed fendbendazole at 100 ppm for 7 days and collected data on hatching percentage of pheasant eggs before and after treatment. Reproductive performance in hen pheasants was not adversely affected.

Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats.

Suberoylanilide hydroxamic acid (SAHA), or vorinostat, is a histone deacetylase inhibitor approved for use as chemotherapy for lymphoma in humans. The goal of this study was to establish pharmacological parameters of SAHA in cats. Our interest in treating cats with SAHA is twofold: as an anticancer chemotherapeutic and as antilatency therapy for feline retroviral infections. Relying solely on data from studies in other animals would be inappropriate as SAHA is partially metabolized by glucuronidation, which is absent in feline metabolism. SAHA was administered to cats intravenously (2 mg/kg) or orally (250 mg/m², ~17 mg/kg) in a cross-over study design. Clinically, SAHA was well tolerated at these dosages as no abnormalities were noted following administration. The pharmacokinetics of SAHA in cats was found to be similar to that of dogs, but the overall serum drug exposure was much less than that of humans at an equivalent dose. The pharmacodynamic effect of an increase in acetylated histone proteins in blood was detected after both routes of administration. An increased oral dose of 60 mg SAHA/kg administered to one animal resulted in a surprisingly modest increase in peak drug concentration, suggesting possible saturation of absorption kinetics. This study provides a foundation for future studies of the clinical efficacy of SAHA in treating feline disease.

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus).

Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of tulathromycin were as follows: C(max) (121.54 ± 19.01 ng/mL); T(max) (12 ± 12-24 h); area under the curve AUC(0→∞) (8324.54 ± 1706.56 ng·h/mL); terminal-phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal-phase rate constant half-life t1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: Cmax (1594 ± 379.23 ng/mL); Tmax (12 ± 12-36 h); AUC(0→∞) (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t(1/2λz) (155.28 h; harmonic). All goats had injection-site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.

Caprine abscess model of tulathromycin concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis following subcutaneous or intrachamber administration.

Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing conditions in livestock and humans. We used an in vivo model to evaluate antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with C. pseudotuberculosis, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from C. pseudotuberculosis-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of C. pseudotuberculosis reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from C. pseudotuberculosis-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the C. pseudotuberculosis isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by C. pseudotuberculosis.

Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle.

The objective of this study was to develop a population pharmacokinetic (PK) model and predict tissue residues and the withdrawal interval (WDI) of flunixin in cattle. Data were pooled from published PK studies in which flunixin was administered through various dosage regimens to diverse populations of cattle. A set of liver data used to establish the regulatory label withdrawal time (WDT) also were used in this study. Compartmental models with first-order absorption and elimination were fitted to plasma and liver concentrations by a population PK modeling approach. Monte Carlo simulations were performed with the population mean and variabilities of PK parameters to predict liver concentrations of flunixin. The PK of flunixin was described best by a 3-compartment model with an extra liver compartment. The WDI estimated in this study with liver data only was the same as the label WDT. However, a longer WDI was estimated when both plasma and liver data were included in the population PK model. This study questions the use of small groups of healthy animals to determine WDTs for drugs intended for administration to large diverse populations. This may warrant a reevaluation of the current procedure for establishing WDT to prevent violative residues of flunixin.

Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos).

Six adult male alpacas received one subcutaneous administration of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. After a washout period, the same alpacas received three subcutaneous doses of 6.6 mg/kg CCFA at 5-day intervals. Blood samples collected from the jugular vein before and at multiple time points after each CCFA administration were assayed for ceftiofur- and desfuroylceftiofur-related metabolite concentrations using high-performance liquid chromatography. Pharmacokinetic disposition of CCFA was analyzed by a noncompartmental approach. Mean pharmacokinetic parameters (± SD) following single-dose administration of CCFA were Cmax (2.7 ± 0.9 µg/mL); Tmax (36 ± 0 h); area under the curve AUC0→∞ (199.2 ± 42.1 µg·h/mL); terminal phase rate constant λz (0.02 ± 0.003/h); and terminal phase rate constant half-life t1/2λz (44.7 h; harmonic). Mean terminal pharmacokinetic parameters (±SD) following three administrations of CCFA were Cmax (2.0 ± 0.4 µg/mL); Tmax (17.3 ± 16.3 h); AUC0→∞ (216.8 ± 84.5 µg·h/mL); λz (0.01 ± 0.003/h); and t1/2λz (65.9 h; harmonic). The terminal phase rate constant and the Tmax were significantly different between single and multiple administrations. Local reactions were noted in two alpacas following multiple CCFA administrations.

Prediction of flunixin tissue residue concentrations in livers from diseased cattle.

Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.

Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats.

Physiologically based pharmacokinetic (PBPK) models, which incorporate species- and chemical-specific parameters, could be useful tools for extrapolating withdrawal times for drugs across species and doses. The objective of this research was to develop a PBPK model for goats to simulate the pharmacokinetics of tulathromycin, a macrolide antibiotic effective for treating respiratory infections. Model compartments included plasma, lung, liver, muscle, adipose tissue, kidney, and remaining poorly and richly perfused tissues. Tulathromycin was assumed to be 50% protein bound in plasma with first-order clearance. Literature values were compiled for physiological parameters, partition coefficients were estimated from tissue:plasma ratios of AUC, and the remaining model parameters were estimated by comparison against the experimental data. Three separate model structures were compared with plasma and tissue concentrations of tulathromycin in market age goats administered 2.5 mg/kg tulathromycin subcutaneously. The best simulation was achieved with a diffusion-limited PBPK model and absorption from a two-compartment injection site, which allowed for low persistent concentrations at the injection site and slower depletion in the tissues than the plasma as observed with the experimental data. The model with age-appropriate physiological parameters also predicted plasma concentrations in juvenile goats administered tulathromycin subcutaneously. The developed model and compilation of physiological parameters for goats provide initial tools that can be used as a basis for predicting withdrawal times of drugs in this minor species.

Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus).

Tulathromycin is a macrolide antimicrobial labeled for treatment of bacterial pneumonia in cattle and swine. The purpose of the present research was to evaluate tissue concentrations of tulathromycin in the caprine species. A tandem mass spectrometry regulatory analytical method that detects the common fragment of tulathromycin in cattle and swine was validated with goat tissues. The method was used to study tulathromycin depletion in goat tissues (liver, kidney, muscle, fat, injection site, and lung) over time. In two different studies, six juvenile and 25 market-age goats received a single injection of 2.5 mg/kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg/kg tulathromycin weekly with three subcutaneous injections. Mean tulathromycin tissue concentrations were highest at injection site samples in all studies and all doses. Lung tissue concentrations were greatest at day 5 in market-age goats while in the multi-dose animals concentrations demonstrated dose-dependent increases. Concentrations were below limit of quantification in injection site and lung by day 18 and in liver, kidney, muscle, and fat at all time points. This study demonstrated that tissue levels in goats are very similar to those seen in swine and cattle.

Pharmacokinetics and preliminary safety evaluation of azithromycin in adult horses.

Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for preliminary evaluation of safety in adult horses. The bioavailability of azithromycin following intragastric administration was 45 ± 12%. Concentrations within peripheral neutrophils and bronchoalveolar macrophages were several fold higher than that of plasma. Mild decreases in appetite (n = 3) and alterations in fecal consistency (n = 3) were noted following repeated oral administration. The pharmacokinetic profiles of azithromycin in adult horses, especially the slow elimination rate and intraneutrophil and intrapulmonary macrophage accumulation, demonstrate that it is conducive to use in this age group. Because of the gastrointestinal alterations noted, further studies are warranted before azithromycin can be recommended for use in adult horses.

Pharmacokinetics of veterinary drugs in laying hens and residues in eggs: a review of the literature.

Poultry treated with pharmaceutical products can produce eggs contaminated with drug residues. Such residues could pose a risk to consumer health. The following is a review of the information available in the literature regarding drug pharmacokinetics in laying hens, and the deposition of drugs into eggs of poultry species, primarily chickens. The available data suggest that, when administered to laying hens, a wide variety of drugs leave detectable residues in eggs laid days to weeks after the cessation of treatment.

Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus).

Tulathromycin, a novel triamilide in the macrolide class, is labeled for treatment of bacterial pneumonia in cattle and swine. This manuscript evaluates pharmacokinetics of tulathromycin in goats. In two different studies, six juvenile and ten market-age goats received a single injection of 2.5 mg/kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg/kg tulathromycin weekly with three subcutaneous injections. Pharmacokinetic parameters estimated from the plasma concentrations from single injections were similar between the two groups of goats and to previously reported parameters in cattle and swine. Mean terminal half-lives were 59.1 ± 7.6 and 61.2 ± 8.7 h for juvenile and market-age goats, respectively. In the multi-dose study, pharmacokinetic parameters estimated from plasma concentrations demonstrated significant differences at P < 0.05 among repeated injections but not among doses. Overall, pharmacokinetic parameters in goats are similar to those reported in cattle and swine, and tulathromycin may prove a useful drug for treating respiratory disease in goats.

Pharmacokinetic-pharmacodynamic integration of orbifloxacin in Japanese quail (Coturnix japonica) following oral and intravenous administration.

The pharmacokinetics of single-dose administration of orbifloxacin were determined in Japanese quail (Coturnix japonica) at dosages of 5 mg/kg intravenous (i.v. n = 12) and 7.5 mg/kg oral (p.o.; n = 5), 10 mg/kg p.o. (n = 5), 15 mg/kg p.o. (n = 12) and 20 mg/kg p.o. (n = 5) via HPLC. Orbifloxacin minimal inhibitory concentrations (MICs) against 22 microbial isolates from various bird species were performed to calculate pharmacodynamic surrogate markers. The concentration-time data were analyzed using a naïve pooled data (NPD) approach and compartmental and noncompartmental methods. Steady-state volume of distribution (Vd(ss)) and total body clearance (Cl) after i.v. administration were estimated to be 1.27 L/kg and 0.60 L/h·kg, respectively. Following 15 and 20 mg/kg p.o. dose, bioavailability was 102% and 117%, respectively. The harmonic mean of the corresponding terminal half-lives (T(1/2) λ(z) ) across all the dose groups was 1.71 h. The C(max) /MIC(90) and AUC(0∞24) /MIC(90) for the 15 and 20 mg/kg p.o. doses were ≥5.22 and ≥8.98, and ≥25.80 and ≥39.37 h, respectively. The results of this study suggest that 20 mg/kg orbifloxacin p.o. would be a rational daily dose to treat susceptible infections in Japanese quail not intended for food consumption. For more sensitive bacterial organisms, 15 mg/kg p.o. may also be effective.