
The influence of the state of pregnancy (days 45, 90, and 135 of gestation) on the pharmacokinetics of levamisole was investigated in ewes. Twelve healthy Merino female sheep were allocated into two groups (n = 6 per group). The ewes in group 1 (non-pregnant) were not mated, while the ewes in group 2 (pregnant) were mated with rams by synchronizing their estrus cycles. Levamisole was injected intramuscularly once at a dose of 7.5 mg/kg into all ewes. Blood samples were taken at 13 different times over a 48-h period according to a defined protocol. Plasma samples were analyzed for levamisole via high-performance liquid chromatography. Pregnant ewes had significantly lower Cmax, AUC0-last, and t1/2ʎz of levamisole than non-pregnant ewes. There were no significant differences in Tmax between the two groups. The values of AUC0-last, Cmax, and t1/2ʎz decreased as pregnancy progressed. These results indicated that pregnancy reduced exposure (AUC0-last) and duration of levamisole presence in the body. This information contributes to the use of levamisole in pregnant ewes, but further studies are needed to determine the change in therapeutic effect related to pregnancy.
Quinidine has long been used for the pharmacological treatment of atrial fibrillation (AF) in horses; however, the plasma concentration required for conversion to sinus rhythm remains unclear. Dominant frequency (DF), derived from surface electrocardiograms, reflects atrial activation rate during AF. This study aimed to quantify the relationship between plasma quinidine concentration and DF using a pharmacokinetic/pharmacodynamic (PK/PD) approach. Ten Thoroughbred horses with naturally occurring AF received quinidine sulfate via a nasogastric tube. Plasma quinidine concentrations and DF values, calculated from digitized atrial fibrillatory segments, were measured during treatment. PK/PD was analyzed using a sigmoid inhibitory Emax model, with typical parameters including a baseline DF of 6.27 Hz, a maximal DF reduction of 3.63 Hz, a theoretical minimum DF of 2.64 Hz, an EC50 of 0.78 μg/mL, and a Hill coefficient of 1.81. Nine horses converted to sinus rhythm, with median DF decreasing from 6.4 Hz to 3.0 Hz immediately before conversion. Model simulations indicated a pharmacodynamic plateau, with an increase in plasma quinidine concentration from 4 to 5 μg/mL resulting in only a 0.06-Hz reduction in DF. A model-predicted plasma quinidine concentration of 2.6 μg/mL achieved a DF of 3.0 Hz and may represent a target concentration for conversion.
L-citrulline is a precursor for endogenous arginine synthesis, supporting nitric oxide production and urea cycle function, yet its pharmacokinetics in neonatal calves are unknown. This study characterized and compared the pharmacokinetics of L-citrulline after intravenous (IV) and oral (PO) administration in healthy neonatal Holstein calves and evaluated associated amino acid responses and short-term clinical and laboratory tolerability. Six healthy male calves (2-4 weeks old) received a single 150 mg/kg dose of L-citrulline as extemporaneously prepared 5% (w/v) IV and 10% (w/v) PO formulations in a randomized 2-period crossover design with a 7-day washout. Blood samples were collected pre-dose and up to 48 h post-dose. Plasma amino acids were quantified by LC-MS/MS, and pharmacokinetic parameters were estimated using non-compartmental analysis. After IV administration, the highest observed total plasma L-citrulline concentration was detected at the first post-dose sampling time, 5 min after bolus administration (Cpeak 2213 ± 629 μmol/L; range, 1329-2830 μmol/L). After PO administration, Cmax was 1107 ± 371 μmol/L (range, 623-1478 μmol/L), with a median Tmax of 60 min (range, 45-120 min). Baseline-corrected non-compartmental analysis yielded t1/2 values of 2.32 ± 0.79 h after IV administration and 2.23 ± 0.60 h after PO administration, with AUC0-∞ values of 4130 ± 558 and 3444 ± 1067 μmol·h/L, respectively. Absolute oral bioavailability was 0.86 ± 0.32 (range, 0.52-1.28). Both routes increased plasma arginine (max +159% IV; +122% PO) and ornithine (max +132% IV; +149% PO) with no clinically relevant adverse effects or laboratory abnormalities during short-term monitoring of clinical, hematological, biochemical, blood gas/electrolyte, and coagulation variables. These findings support further evaluation of L-citrulline as a nutritional and/or therapeutic supplement in neonatal calves.
ABSTRACT This study aimed to determine the pharmacokinetics of nalbuphine following intravenous (IV) or intramuscular (IM) administration in six adult H&N Brown chickens anesthetized with isoflurane. In a randomized crossover study, nalbuphine (12.5 mg/kg) was administered IV and IM to isoflurane‐anesthetized chickens (end‐tidal isoflurane concentration: 1.2%–1.4%), with 1‐week intervals between experiments. Blood samples were collected immediately before and at predetermined time points up to 480 min after administration. Plasma concentrations were determined by liquid chromatography–mass spectrometry, and models were fitted to plasma concentration versus time data. Cardiovascular variables were recorded concurrently at the same time points. A three‐compartment model best described nalbuphine plasma concentration changes. Estimated distribution volumes were 1.4 L/kg for the central compartment and 0.57 and 2.5 L/kg for the first and second peripheral compartments, respectively. Metabolic clearance was 7.59 L/kg/h, and distribution clearances were 0.25 and 11 L/kg/h for the first and second peripheral compartments, respectively. Bioavailability after IM administration was 98%. The plasma concentration at time zero was 11.81 mg/L. Heart rate slightly decreased at 4 and 8 min after IV or IM drug administration. Nalbuphine exhibited a high volume of distribution and clearance in isoflurane‐anesthetized chickens, and demonstrated excellent bioavailability after IM administration.
Diazepam (DZP), a benzodiazepine sedative, has been increasingly detected in various aquatic products including fish, shrimp, and crab in recent surveillance studies, raising public health concerns. This study systematically investigates the residue behavior, metabolite profile, and dietary risk of DZP in grass carp (Ctenopharyngodon idella) following oral administration at a dose of 500 μg/kg body weight. Concentrations of DZP and its metabolites in plasma and tissues were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the drug concentration-time data were fitted using a non-compartmental model embedded in WinNonLin 6.1 pharmacokinetic software. The results indicate that DZP exhibits prolonged elimination kinetics, with tissue elimination half-lives (T1/2λz) ranging from 309.44 to 509.75 h, and residues in skin-on muscle did not fall below the limit of quantification until 98 days. Metabolite analysis identified nordiazepam as the primary metabolite, with its concentration surpassing that of the parent compound by Day 21 post-administration, establishing it as a reliable residue marker for DZP in grass carp. The peak human health risk index (HRI) value was 0.392 on Day 4, remaining above the alert threshold (HRI ≥ 0.1) for 21 days, though all values remained below the safety limit (HRI < 1). These findings provide critical data to support the regulation of aquaculture practices and the assessment of dietary exposure risks associated with DZP-contaminated aquatic products.
This exploratory randomized crossover study investigated pharmacokinetic interactions, functional alertness, and cardiovascular safety of tasipimidine oral solution administered alone and in combination with fluoxetine in healthy Beagle dogs (n = 8; 4 dogs per dose level), with a 7-day washout between phases. Dogs received single oral doses of tasipimidine (20 or 30 μg/kg) alone and following single or repeated fluoxetine administration (~1 mg/kg/day for 12 days). Functional alertness was assessed using a semi-quantitative, observer-based scale evaluating responsiveness and ability to walk. Cardiovascular effects were monitored by telemetry, including heart rate, blood pressure, and ECG. Co-administration with fluoxetine increased tasipimidine exposure, with Cmax and AUC0-24h rising approximately 1.3-1.4-fold after single fluoxetine dosing and up to 1.4-fold at the 30 μg/kg tasipimidine dose after repeated fluoxetine administration; these changes were variable and not consistently statistically significant. Reduced alertness and transient mild ataxia were more frequent at 30 μg/kg, whereas the 20 μg/kg dose showed minimal sedative effects. Tasipimidine reduced heart rate by 30-52 bpm and mean arterial pressure by 13-21 mmHg. No clinically relevant ECG abnormalities were detected. The increased tasipimidine exposure is likely related to metabolic inhibition by fluoxetine. Overall, concurrent use was well tolerated, supporting a reduced tasipimidine dose (20 μg/kg) when combined with fluoxetine.
Cyclooxygenases (COX-1 and COX-2) are key enzymes in the biosynthesis of prostanoids, which mediate physiological functions, inflammation, and the process of carcinogenesis. In dogs and cats, lower urinary tract diseases are prevalent and often complex, requiring targeted therapeutic interventions. Although the role of cyclooxygenases is well established in humans, their expression profile in dogs and cats remains underexplored. This systematic review aimed to consolidate the available knowledge regarding the expression of COX-1 and COX-2 in the lower urinary tract tissues of dogs and cats, highlighting pathological implications and gaps in the literature. A total of 28 original studies were included in this review, which employed methodologies such as immunohistochemistry (IHC), Western blotting (WB), in situ hybridization (ISH), RNA sequencing, and ELISA. The urinary bladder was the most frequently analyzed tissue, followed by the urethra. COX-2 expression was predominantly elevated in tissues with inflammation or neoplasia, whereas COX-1 exhibited a constitutive expression pattern in normal tissues. In cats with feline idiopathic cystitis (FIC), COX-2 expression was significantly elevated in the urethral mucosa. In cases of transitional cell carcinoma (TCC), COX-2 expression varied substantially. The consistent expression of COX-1 in both normal and altered tissues suggested a homeostatic role. Despite the potential of COX-2 as a therapeutic target and prognostic marker, methodological heterogeneity, small sample sizes, and the lack of standardized criteria limit the comparability of findings. This review underscores the need for well-designed studies and standardized approaches to better understand the role of COX enzymes in the uropathology of small animals.
Clonidine is an α-2 agonist shown to be both well tolerated and useful in the treatment of canine fear-based disorders, although it is perceived to have a short duration of action. Clonidine is available in regular release and extended-release formulations, but canine pharmacokinetic (PK) and pharmacodynamic (PD) data on any clonidine formulation are lacking. The aim of this study was to establish PK and PD parameters of regular release (RR) clonidine in dogs. Clonidine RR (n = 6) was orally administered at 0.05 mg/kg to laboratory beagles. Clonidine RR showed a maximum concentration (Cmax) 1.5-2 h after administration and declined to below the level of quantification over 4-8 h after administration with an elimination half-life (T1/2) of 0.65 h. Slight reductions in heart rate and increases in sedation scores were seen in all treatment groups. In conclusion, obtained data indicated a single dose of clonidine RR at 0.05 mg/kg was well tolerated with mild sedation and bradycardia and no other adverse effects in healthy dogs.
The misuse and abuse of veterinary anesthetic and analgesic agents pose significant public health risks, particularly with the growing presence of ultrapotent opioids and other anesthetics in the illicit drug trade. In response, there is increasing emphasis on incorporating medication safety training into veterinary curricula. This paper has two main objectives: first, to describe an evidence-based, interprofessional simulation activity designed to raise awareness about the diversion and misuse of veterinary opioids and alpha-2 agonists, while also developing basic life support skills for responding to accidental exposure; second, to propose three veterinary medication safety education sub-competencies aligned with CBVE Domain 4 and proposed discipline-level pharmacology competencies. These are aimed at equipping veterinary students to mitigate human health risks arising from exposure to veterinary medications, especially ultrapotent opioids and alpha-2 agonists.
Tapentadol is a dual mechanism analgesic utilizing both μ-opioid receptor (MOR) agonism and norepinephrine reuptake inhibition (NRI). This study evaluated the pharmacokinetics and pharmacodynamics of tapentadol as a potential analgesic with the goal of treating pain in horses. Pharmacokinetics of both tapentadol and tapentadol-O-glucuronide were elucidated. Six horses received three separate escalating single oral doses (1, 3, and 5 mg/kg) and a single intravenous (0.32 mg/kg) dose of tapentadol in a four-period sequential design. Concentrations of tapentadol and tapentadol-O-glucuronide were determined using liquid chromatography-tandem mass spectrometry. The maximum concentrations (mean ± SD) in plasma following administration of 1, 3, 5 mg/kg oral tapentadol were 7.98 ± 6.95, 39.8 ± 53.8, and 210.6 ± 234.4 ng/mL at 0.75, 0.63, and 0.38 h, respectively. Maximum plasma concentration (mean ± SD) after a single 0.32 mg/kg IV dose was 339.2 ± 83.5 ng/mL. The maximum concentrations of tapentadol-O-glucuronide following single 1, 3, and 5 mg/kg oral doses and a single 0.32 mg/kg IV dose of tapentadol were 532.6 ± 171.4, 1169.4 ± 345.4, 1559.5 ± 574.6, and 226.4 ± 51.5 ng/mL at times 6.0, 6.0, 7.0, and 0.5 h. Tapentadol was well-tolerated at all doses.
Veterinary students often find it difficult to select antimicrobial drugs for patients, likely because it requires them to consider multiple factors and there are frequently several possible options with a lack of a defined "correct or incorrect" choice. Our goal was to develop a teaching tool to engage the students through the decision-making processes associated with antimicrobial drug selection in cats and dogs, designed to align with the CBVE competency of explaining a justification. We developed a series of small animal case vignettes with a set of antimicrobial choices. The students use a visual analogue scale (VAS) to indicate the relative safety and/or efficacy of the drug in question; they also provide a written justification for their selection. Student responses are anonymized and downloaded for instructor review. The instructor categorizes the frequency of selections according to the labeled quartiles and displays the results as a bar graph during the classroom session and selects some written justifications for the class to view as a group. Practical considerations for tool implementation include considerations of the curriculum, time spent reviewing individual answers, and the tool's utility as a supplementary aid to foster more student discourse about topics in pharmacology. Overall, the VAS tool has the potential to aid in generating discussion in clinical contexts where there is not a single best answer.
Aging may modify the pharmacokinetic disposition and excretion of gentamicin, although drug dose adjustments in aged horses are uncommon in clinical practice. Since high-dose, once daily dosing of gentamicin is considered therapeutically most effective, a comparative single-dose study was conducted to evaluate the differences in pharmacokinetics between healthy young-adult (5-10 years) and geriatric (≥ 25 years) horses receiving 6.6 mg/kg gentamicin intravenously. Blood samples were collected at designated time-points following drug administration and frozen at -80°C until assayed by a validated immunoassay. Gentamicin plasma concentrations versus time plots were analyzed by noncompartmental analysis using commercial software (WinNonlin-v8.4). Baseline physical examination and hematological parameters did not differ between age groups, except for a lower mean bodyweight in the geriatric group (477 ± 4 kg vs. 402 ± 6 kg). None of the pharmacokinetic parameters were statistically different between age groups. The oldest geriatric horse (41 years) had a longer half-life and lower clearance of 5.3 h and 22.79 L/h, respectively, compared to a range of 1.39-2.56 h and 26.39-40.59 L/h for the remainder of the geriatric group (25-29 years). Further studies may be indicated in horses > 30 years old to determine if dose reduction is necessary in this population.
This study evaluated the pharmacokinetics of an extended-release buprenorphine formulation (Ethiqa XR) in dogs and explored potential sex differences. Twelve healthy intact beagles (6 males and 6 females) received a single subcutaneous injection of Ethiqa XR (0.2 mg/kg). Blood samples were collected up to 168 h post-administration, and plasma buprenorphine concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital signs, sedation, and nausea scores were recorded. Therapeutic plasma concentrations were sustained for approximately 60-90 h in both sexes, depending on the therapeutic threshold used (0.6 or 1.0 ng/mL). Although no significant differences in pharmacokinetics were detected, drug exposure and elimination were greater in females: median peak plasma buprenorphine concentrations (male: 1.6 ng/mL, female: 2.9 ng/mL); median terminal half-life (male: 36.6 h, female: 24.7 h); area under the curve (AUC 0-12 h) (male: 12.8 h*ng/mL, female: 16.9 h*ng/mL); AUC (0-96 h) (male: 94.4 h*ng/mL, female: 137.7 h*ng/mL). Time to maximum concentrations were 24 h in both sexes. Higher buprenorphine concentrations were associated with decreased body temperature and heart rate in both sexes and positively correlated with nausea and sedation scores, but only in females. Ethiqa XR administration resulted in therapeutic plasma concentrations up to 90 h, suggesting it may be an alternative option for post-operative pain control.
Equine protozoal myeloencephalitis can cause acute infections with rapid onset of neurologic signs, necessitating immediate empiric therapy with antiprotozoal medication. The objective of the study was to identify when concentrations of diclazuril reached the MIC of Sarcocystis neurona in CSF (1 ng/mL) of healthy adult horses after a single oral dose. Six healthy adult horses were used. Blood and CSF were collected from indwelling intravenous jugular catheters and intrathecal catheters in the lumbosacral space prior to drug administration and then at 1-, 4-, 8-, 12-, 16-, 24-, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h post-administration of a 1 mg/kg dose of pelleted diclazuril administered by mouth in 8 oz of sweet feed. Samples were centrifuged then plasma and CSF supernatant were separated and frozen at -80°C until analysis. Diclazuril concentrations were analyzed with a liquid chromatography-mass spectrometer assay developed specifically for this study. Plasma concentrations of diclazuril peaked at 48 h with a mean concentration of 395.6 ± 109.4 ng/mL. CSF concentrations of diclazuril peaked at 24 h (mean concentration 9.0 ± 5.4 ng/mL) but achieved the MIC of S. neurona 12 h after administration (mean concentration 2.6 ± 1.8 ng/mL) and remained above MIC for the duration of the sampling period. In conclusion, pelleted diclazuril at 1 mg/kg reaches concentrations in the CSF above the MIC for S. neurona in healthy horses 12 h after a single oral dose.
This study characterized the long-term pharmacokinetic profile of a 1% fipronil pour-on formulation in Nellore bulls under field conditions. Seventeen animals received a single topical dose (1 mg/kg), and plasma concentrations of fipronil and its metabolites (sulfone and desulfinyl) were monitored for 175 days using LC-MS/MS. Fipronil was rapidly absorbed, reaching a maximum concentration Cmax of 42.3 ± 4.1 ng/mL on day 1, but became undetectable by day 35. Conversely, fipronil sulfone was the predominant systemic analyte, reaching Cmax 60.2 ± 5.6 ng/mL on day 13 and persisting for up to 140 days. The metabolite-to-parent AUC0-t ratio (6.2) and the protracted terminal phase are consistent with flip-flop kinetics, where systemic persistence is governed by slow release from the dermal/sebaceous reservoir rather than metabolic clearance. Fipronil desulfinyl was sporadically detected at low levels, confirming that in vivo photodegradation occurs on the animal's surface. These findings consolidate fipronil sulfone as the most reliable marker residue for food safety assessments. Furthermore, the sporadic detection of fipronil desulfinyl confirms that in vivo photodegradation occurs under field conditions, warranting further investigation regarding its contribution to residue dynamics in cattle.
At the Texas A&M University College of Veterinary Medicine (TAMU-CVM), the veterinary pharmacology faculty and library faculty have collaborated to teach aspects of Evidence-Based Veterinary Medicine (EBVM) since 2010. These skills are integral to drug and therapeutic decision-making and are required for veterinary graduate Day-One competency. Herein, we explain the progression of incorporation of EBVM teaching at TAMU-CVM to make clear that the development of teaching and assessment activities did not occur as a single design exercise, but rather in an iterative and reflective manner over several years. We describe the courses in which we have one or more lecture or laboratory sessions focused on scaffolding the skills of EBVM across 3 semesters, including the skills of writing clinical questions, searching the biomedical literature for evidence, critically appraising the evidence, and then applying the evidence to answer the clinical question to make a clinical recommendation. We share the specific contributions of the librarians and the pharmacologist in creating opportunities for students to develop the competencies of EBVM.
This research studied dose-dependent changes in the pharmacokinetics of enrofloxacin (ENR) and its active metabolite, ciprofloxacin (CIP), in calves. The research was performed on eighteen calves utilizing a parallel pharmacokinetic approach. Calves were divided into three distinct dosage groups, receiving intravenous administration of ENR at doses of 2.5, 5, and 10 mg/kg, respectively. Blood samples were collected at 15 specified intervals during a 48-h duration. ENR and CIP plasma concentrations were quantified by HPLC. Pharmacokinetic data was obtained using non-compartmental analysis. The area under the concentration-time curve from 0 to last (AUC(0-last))/dose of ENR increased in a dose-dependent manner. The elimination half-life of ENR was prolonged from 2.41 to 3.47 h (p < 0.05). The total body clearance decreased significantly with the dose increase (p < 0.05), while the volume of distribution at steady state remained comparable across dosage groups (p > 0.05). The AUC(0-last) of CIP increased in a dose-dependent manner (p < 0.05), but no alteration was found in the conversion ratio of ENR to CIP (26%-28%, p > 0.05). The results of the current investigation demonstrated that the pharmacokinetics of ENR and CIP in calves had considerable variability with dose. Assessing dose-dependent pharmacokinetic alterations in calves can aid in establishing the dosing regimen; however, additional research is required to confirm dose-dependent therapeutic efficacy and safety.
This study compared tear film exposure and retention of four chloramphenicol ophthalmic formulations in dogs, evaluating the effects of drug concentration (0.2% to 5%) and vehicle type (solution vs. ointment). Eight healthy dogs were enrolled in a randomized paired-eye crossover study consisting of two sessions with a 7-day washout. Tear samples were collected via microcapillary tubes at intervals up to 480 min post-instillation, and concentrations were quantified using UV-Vis spectrophotometry. Results showed that chloramphenicol exposure was significantly enhanced by higher concentrations and ointment vehicles. The 0.8% solution achieved a 2.2-fold increase in AUC0-480 over the 0.2% solution, while the 5% ointment provided a 3.0-fold increase over the 1% ointment. Tear concentration at 480 min was superior for ointments, with the 5% formulation maintaining 88.7 ± 6.8 μg/mL, whereas both solutions fell below quantification limits by the end of the interval. Overall exposure did not differ significantly between the 0.8% solution and 1% ointment. In conclusion, chloramphenicol exposure on the ocular surface depends on both concentration and formulation. High-concentration ointments maximize exposure and prolong retention, providing a pharmacokinetic framework for optimizing therapy in canine bacterial keratitis.
This study aimed to compare the pharmacokinetic profile of the active dipyrone metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA) administered alone and in combination with tramadol in dogs. Nine mixed-breed dogs, weighing 15.33 ± 2.25 kg, participated in a two-treatment crossover design: G1 received intravenous dipyrone (25 mg kg-1) and G2 received dipyrone (25 mg kg-1) combined with tramadol (2 mg kg-1), with a 15-day washout. Blood samples were collected up to 48 h and plasma concentrations analyzed using UPLC-MS/MS. Pharmacokinetic parameters were calculated using PKSolver 2.0. Normally distributed data were analyzed with the t-test, and non-normal data with the Mann-Whitney test (p < 0.05); parameters with significant differences were subjected to Pearson correlation. Analyses were performed using Python. For MAA, Cmax and C0 differed significantly. For AA, AUC0-t, AUC0→∞, Cl, and MRT0→∞ differed significantly. Tramadol and its metabolites were also described. The pharmacokinetic interaction between dipyrone and tramadol increased systemic exposure (AUC) of AA and inhibited the conversion of tramadol to M1, without direct changes in the severe adverse effects associated with MAA. Further studies involving nociceptive stimuli and multiple-dose regimens are needed to assess clinical relevance.
Ceftiofur is a third-generation cephalosporin widely used in veterinary medicine; however, pharmacokinetic data in rabbits remain limited. This study aimed to characterize the pharmacokinetics of ceftiofur in rabbits following single intravenous (IV) and intramuscular (IM) administration and to evaluate its potential antibacterial efficacy using pharmacokinetic/pharmacodynamic (PK/PD) indices. Ceftiofur was administered at a dose of 2 mg/kg body weight (BW) via IV and IM routes. Plasma ceftiofur-related concentrations (expressed as desfuroylceftiofur acetamide, DCA) were quantified using a validated analytical method, and pharmacokinetic parameters were determined by noncompartmental analysis. Following IM administration, ceftiofur was rapidly absorbed, with a median time to peak concentration (Tmax) of 2 h and a high absolute bioavailability (88.72%). The drug exhibited moderate distribution, with a volume of distribution (VZ) of 1.93 L/kg and a steady-state volume of distribution (VSS) of 0.85 L/kg, and was eliminated slowly, with a systemic clearance of 0.083 L/h/kg. The mean residence time (MRT; 9.95 h) after IM administration was not longer than that observed after IV administration (10.34 h), precluding reliable estimation of the absorption half-life. Based on PK/PD analysis assuming a minimum inhibitory concentration (MIC) of ≤ 1.0 μg/mL, the calculated time above MIC (T > MIC) values following single IV and IM administration were approximately 4 and 5 h, respectively. These results indicate that although ceftiofur is rapidly and extensively absorbed in rabbits, a single IV or IM dose of 2 mg/kg BW may be insufficient to achieve effective exposure against bacterial pathogens with MIC values ≥ 1.0 μg/mL.