The aim of this article was to evaluate the influence and effects of chosen bioaccumulative substances i.e. heavy metals, pesticides, and polychlorinated biphenyls (PCBs) on fish, as well as provide information on time trends and potential threat to human health. Chemical substances which pollute water may affect living organisms in two ways. First of all, large amounts of chemical substances may cause sudden death of a significant part of the population of farmed fish, without symptoms (i.e. during breakdown of factories or industrial sewage leaks). However, more frequently, chemical substances accumulate in tissues of living organisms affecting them chronically. Heavy metals, pesticides, and polychlorinated biphenyls are persistent substances with a long-lasting biodegradation process. In a water environment they usually accumulate in sediments, which makes them resistant to biodegradation processes induced by, e.g., the UV light. These substances enter the fish through direct consumption of contaminated water or by contact with skin and gills. Symptoms of intoxication with heavy metals, pesticides, and PCBs may vary and depend on the concentration and bioavailability of these substances, physicochemical parameters of water, and the fish itself.

OBJECTIVE To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs. ANIMALS 7 healthy adult Beagles. PROCEDURES In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured. RESULTS Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects.

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.

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 determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.

OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells. For experiment 2, minocycline was administered intragastrically (4 mg/kg, q 12 h, for 5 doses) to 6 horses. Plasma samples were obtained before and 20 times within 96 hours after minocycline administration. A BAL was performed 6 times within 72 hours after minocycline administration for collection of PELF samples and BAL cells. RESULTS Mean bioavailability of minocycline was 48% (range, 35% to 75%). At steady state, mean ± SD maximum concentration (Cmax) of minocycline in plasma was 2.3 ± 1.3 μg/mL, and terminal half-life was 11.8 ± 0.5 hours. Median time to Cmax (Tmax) was 1.3 hours (interquartile range [IQR], 1.0 to 1.5 hours). The Cmax and Tmax of minocycline in the PELF were 10.5 ± 12.8 μg/mL and 9.0 hours (IQR, 5.5 to 12.0 hours), respectively. The Cmax and Tmax for BAL cells were 0.24 ± 0.1 μg/mL and 6.0 hours (IQR, 0 to 6.0 hours), respectively. CONCLUSIONS AND CLINICAL RELEVANCE Minocycline was distributed into the PELF and BAL cells of adult horses.

OBJECTIVE To evaluate pharmaceutical characteristics (strength or concentration, accuracy, and precision), physical properties, and bacterial contamination of fluconazole compounded products. SAMPLE Fluconazole compounded products (30- and 240-mg capsules; 30- and 100-mg/mL oral suspensions) from 4 US veterinary compounding pharmacies. PROCEDURES Fluconazole compounded products were ordered 3 times from each of 4 pharmacies at 7- or 10-day intervals. Generic fluconazole products (50- and 200-mg tablets; 10- and 40-mg/mL oral suspensions) served as references. Compounded products were evaluated at the time of receipt; suspensions also were evaluated 3 months later and at beyond-use dates. Evaluations included assessments of strength (concentration), accuracy, precision, physical properties, and bacterial contamination. Acceptable accuracy was defined as within ± 10% of the labeled strength (concentration) and acceptable precision as within ± 10%. Fluconazole was quantified by use of high-performance liquid chromatography. RESULTS Physical characteristics of compounded products differed among pharmacies. Aerobic bacterial cultures yielded negative results. Capsules (30 and 240 mg) had acceptable accuracy (median, 96.3%; range, 87.3% to 135.2%) and precision (mean ± SD, 7.4 ± 6.0%). Suspensions (30 and 100 mg/mL) had poor accuracy (median, 73.8%; range, 53.9% to 95.2%) and precision (mean ± SD, 15.0 ± 6.9%). Accuracy and precision were significantly better for capsules than for suspensions. CONCLUSIONS AND CLINICAL RELEVANCE Fluconazole compounded products, particularly suspensions, differed in pharmaceutical and physical qualities. Studies to evaluate the impact of inconsistent quality on bioavailability or clinical efficacy of compounded fluconazole products are indicated, and each study should include data on the quality of the compounded product evaluated.

OBJECTIVE To determine the pharmacokinetics of meloxicam after single IV and IM injections in red-eared slider turtles (Trachemys scripta elegans). ANIMALS 8 healthy red-eared slider turtles. PROCEDURES Turtles received 1 dose of meloxicam (0.2 mg/kg) IV or IM (4 turtles/route), a 30-day washout period was provided, and then turtles received the same dose by the opposite route. Blood samples were collected at predetermined times for measurement of plasma meloxicam concentration. Pharmacokinetic values for each administration route were determined with a 2-compartment open model approach. RESULTS For IV administration, mean ± SD values of major pharmacokinetic variables were 1.02 ± 0.41 hours for distribution half-life, 9.78 ± 2.23 hours for elimination half-life, 215 ± 32 mL/kg for volume of distribution at steady state, 11.27 ± 1.44 μg•h/mL for area under the plasma concentration versus time curve, and 18.00 ± 2.32 mL/h/kg for total body clearance. For IM administration, mean values were 0.35 ± 0.06 hours for absorption half-life, 0.72 ± 0.06 μg/mL for peak plasma concentration, 1.5 ± 0.0 hours for time to peak concentration, 3.73 ± 2.41 hours for distribution half-life, 13.53 ± 1.95 hours for elimination half-life, 11.33 ± 0.92 μg•h/mL for area under the plasma concentration versus time curve, and 101 ± 6% for bioavailability. No adverse reactions were detected. CONCLUSIONS AND CLINICAL RELEVANCE Long half-life, high bioavailability, and lack of immediate adverse reactions of meloxicam administered IM at 0.2 mg/kg suggested the possibility of safe and effective clinical use in turtles. Additional studies are needed to establish appropriate administration frequency and clinical efficacy.

OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. ANIMALS 12 healthy adult dogs.PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m2) or OTM (1 mg/m2) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m2) or detomidine gel by OTM administration (0.5 mg/m2), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.