Introduction: Quercetin is a polyphenolic flavonoid which has been used in traditional Chinese medicine as a natural therapeutic agent with a broad spectrum of activities (antioxidant, anticancer, neuroprotective, anti-inflammatory, antiviral and antibacterial). The aim of this study was to develop and validate a rapid and simple ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for the determination of quercetin in milk. Material and Methods: Sample preparation was based on a liquid-liquid extraction with 0.5% formic acid in acetonitrile. The chromatographic separation was performed on a ZORBAX SB-C18 column with methanol and 0.5% formic acid as a mobile phase. Results: The procedure was successfully validated. The mean recovery of the analyte was 98%, with the corresponding intra- and inter-day variation less than 10% and 15%, respectively, and the repeatability and reproducibility were in the range of 3%–7.2% and 6.1%–12%, respectively. The lowest level of quantification was 1.0 μg/kg. Conclusion: The proposed method was successfully applied in evaluating the pharmacokinetics of quercetin in milk obtained from dairy cows with clinical mastitis after intramammary administration.

Objective: We performed a randomized two-way crossover study to evaluate the pharmacokinetic profiles of two high-dose ascorbic acid (AA) after IV infusion in healthy beagle dogs. Materials and Methods: The dogs were administered IV AA at two doses of 1.5 and 3 gm/kg for 4 h, and the AA concentration in plasma and urine pH was measured before and after administration. Results: The plasma concentrations of AA in both groups peaked 3 h after administration. Among the two groups, the urine pH was not significantly different (p = 0.12990.7944). High-dose IV AA did not induce serious adverse events in dogs. Conclusion: The results of this study suggest that the high dose of AA which reaches the therapeutic dose for cancer and supports the safety of high-dose IV AA in dogs. [J Adv Vet Anim Res 2019; 6(4.000): 481-485]

Objective: The object of the study was to examine the major pharmacokinetic parameters after a single application of a complex drug preparation for veterinary use based on fipronil, praziquantel, moxidectin, and pyriproxyfen in cats and dogs.Materials and Methods: For dogs, the drug preparation was administered spot-on solution in the following dosage of active pharmaceutical substances: fipronil 27.0 mg/kg body weight (bwt), praziquantel 10.8 mg/kg bwt, moxidectin 6.75 mg/kg bwt, and pyriproxyfen 5.4 mg/kg bwt; for cats, the dosage was the following: fipronil 43.2 mg/kg bwt, praziquantel 17.28 mg/kg bwt, mox-idectin 4.32 mg/kg bwt, and pyriproxyfen 8.64 mg/kg bwt. The blood samples were taken from dogs and cats. The principle of the method for determining praziquantel, trans-4-hydroxyprazi-quantel, pyriproxyfen, and fipronil in serum samples was chromatographed in a high-pressure liquid chromatograph with detection by means of a mass-spectrometric detector. The moxidectin content of the blood was detected by high-performance liquid chromatography.Results: The drug preparation active substances: praziquantel, fipronil, and moxidectin are absorbed into the blood of dogs and cats. The penetration of praziquantel into the systemic circulation and further into organs and tissues was proved. After topical administration, moxidectin is absorbed and distributed systemically and is slowly removed from the plasma, which manifests itself in detectable concentrations of moxidectin in the blood for 1 month.Conclusion: The present results of pharmacokinetic investigations may promote to the determination of effective therapy strategy and prophylaxis of parasitic diseases in dogs and cats. [J Adv Vet Anim Res 2019; 6(1.000): 25-32]

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

OBJECTIVE: To determine the pharmacokinetics of a single oral dose of trazodone and its effect on the activity of domestic pigeons (Columba livia). ANIMALS: 6 healthy adult male domestic pigeons. PROCEDURES: During the first of 3 experiments, birds received orally administered trazodone at doses ranging from 3 to 30 mg/kg to determine the dose for subsequent experiments. During the second experiment, each bird received 1 dose of trazodone (30 mg/kg, PO). Blood was collected for determination of plasma trazodone concentration before and at predetermined times for 24 hours after drug administration. Pharmacokinetic parameters were calculated by noncompartmental analysis. During experiment 3, birds were instrumented with ultralightweight accelerometers and received orally administered trazodone (30 mg/kg) or an equal volume of water twice at a 48-hour interval. Activity of birds was monitored for 24 hours after administration of each treatment. RESULTS: No adverse effects were observed. Mean ± SD terminal half-life of trazodone was 5.65 ± 1.75 hours. Plasma trazodone concentrations remained > 0.130 μg/mL for approximately 20 hours. Trazodone did not affect the activity of birds during the first 2 and 15 hours after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that oral administration of 1 dose (30 mg/kg) of trazodone to healthy pigeons was safe and resulted in plasma drug concentrations that were similar to those considered therapeutic in humans and dogs for up to 20 hours. Further research is necessary to characterize the pharmacokinetics for repeated doses as well as the clinical effects of trazodone in birds with behavior problems.

OBJECTIVE To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. ANIMALS 6 healthy adult mixed-breed dogs. PROCEDURES In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. RESULTS Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

OBJECTIVE To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.

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.

OBJECTIVE To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved plasma levofloxacin concentration would be sufficient to treat susceptible bacterial infections. ANIMALS 6 healthy adult Beagles. PROCEDURES Levofloxacin was administered orally as a generic 250-mg tablet (mean dose, 23.7 mg/kg) or IV as a solution (15 mg/kg) to each dog in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected at various points for measurement of plasma levofloxacin concentration via high-pressure liquid chromatography. Pharmacokinetic analysis was performed with compartmental modeling. RESULTS After oral administration of the levofloxacin tablet, mean (coefficient of variation) peak plasma concentration was 15.5 μg/mL (23.8%), mean elimination half-life was 5.84 hours (20.0%), and mean bioavailability was 104% (29.0%). After IV administration, mean elimination half-life (coefficient of variation) was 6.23 hours (14.7%), systemic clearance was 145.0 mL/kg/h (22.2%), and volume of distribution was 1.19 L/kg (17.1%). CONCLUSIONS AND CLINICAL RELEVANCE In these dogs, levofloxacin was well absorbed when administered orally, and a dose of approximately 25 mg/kg was sufficient to reach pharmacokinetic-pharmacodynamic targets for treating infections with susceptible Enterobacteriaceae (ie, ≤ 0.5 μg/mL) or Pseudomonas aeruginosa (ie, ≤ 1 μg/mL) according to clinical breakpoints established by the Clinical and Laboratory Standards Institute.

OBJECTIVE To determine the pharmacokinetics and adverse effects of maropitant citrate after IV and SC administration to New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS 11 sexually intact (3 males and 8 females) adult rabbits. PROCEDURES Each rabbit received maropitant citrate (1 mg/kg) IV or SC. Blood samples were collected at 9 (SC) or 10 (IV) time points over 48 hours. After a 2-week washout period, rabbits received maropitant by the alternate administration route. Pharmacokinetic parameters were calculated. Body weight, food and water consumption, injection site, mentation, and urine and fecal output were monitored. RESULTS Mean ± SD maximum concentration after SC administration was 14.4 ± 10.9 ng/mL and was detected at 1.25 ± 0.89 hours. Terminal half-life after IV and SC administration was 10.4 ± 1.6 hours and 13.1 ± 2.44 hours, respectively. Bioavailability after SC administration was 58.9 ± 13.3%. Plasma concentration at 24 hours was 2.87 ± 1.69 ng/mL after IV administration and 3.4 ± 1.2 ng/mL after SC administration. Four rabbits developed local dermal reactions at the injection site after SC injection. Increased fecal production was detected on the day of treatment and 1 day after treatment. CONCLUSIONS AND CLINICAL RELEVANCE Plasma concentrations of rabbits 24 hours after SC and IV administration of maropitant citrate (1 mg/kg) were similar to those of dogs at 24 hours. Reactions at the SC injection site were the most common adverse effect detected. Increased fecal output may suggest an effect on gastrointestinal motility. Additional pharmacodynamic and multidose studies are needed.