Analysis of US Marketed Artemisinin Supplements for Use in Dogs.

Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni. However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high-performance liquid chromatography method validated in our laboratory. We found that the four artemisinin-labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.

Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii).

Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (Cmax) was 0.33 µg/mL with an elimination half-life (Ke t½) of 31.53 h. In CSL, Cmax was 0.17 µg/mL with Ke t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.

The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six-day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single-dose administration but may be significant in horses receiving long-term MMF treatment.

Effects of storage up to 1 year on the in vitro antimicrobial activity of preformulated antibiotic-impregnated calcium sulfate beads.

OBJECTIVE: To compare antimicrobial activity as demonstrated by the zone of inhibition (ZOI) produced by antibiotic-impregnated calcium sulfate (CaSO4 ) beads after storage for 0, 3, 6, 9, and 12 months. STUDY DESIGN: Controlled laboratory study. SAMPLE POPULATION: Three-millimeter diameter CaSO4 beads impregnated with vancomycin (125 mg/mL), or amikacin (250 mg/mL), or without antibiotic (control). METHODS: Calcium sulfate beads were created at the onset of the study. Individual beads were separated in sterile containers and stored in a closed cabinet at room temperature and humidity for 0, 3, 6, 9, or 12 months until testing. The ZOI against methicillin-resistant Staphylococcus pseudintermedius, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa was recorded with serial replating on a fresh lawn of bacteria every 24 h until beads failed to produce a ZOI. The ZOIs and their changes were compared with mixed-effects linear models. Eluted concentrations of vancomycin measured with high-performance liquid chromatography were reported. RESULTS: At 24 h, ZOIs were comparable regardless of time since formulation, except vancomycin against P. aeruginosa, which failed to generate a ZOI. The daily changes of ZOI and duration of activity of antibiotics did not vary between storage length (p > .05). There was no consistent change in eluted drug concentration between storage length of beads. CONCLUSION: Light protected storage at room temperature for up to 12 months did not impair the in vitro activity of antibiotic-impregnated CaSO4 beads, as demonstrated through ZOIs. CLINICAL SIGNIFICANCE: When stored correctly, antibiotic-impregnated CaSO4 beads can be used at least up to 12 months after formulation.

PHARMACOKINETICS OF RECTALLY AND ORALLY ADMINISTERED LEVOFLOXACIN IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Appropriate and effective antibiotic use is a critical component of veterinary medicine, but there are variations across species regarding dosage and administration of these drugs. Oral or rectal routes of administration are typically used in elephants, but not all medications can achieve adequate concentrations rectally. The fluoroquinolone antimicrobials are used in elephants because of their favorable antimicrobial spectrum and pharmacokinetics compared with other oral agents. They are commonly used as part of multiple antibiotic regimens for the treatment of tuberculosis (Mycobacterium tuberculosis). The objective of this study was to determine the pharmacokinetic profile of levofloxacin after oral and rectal administration in Asian elephants (Elephas maximus). Dosages of 5 mg/kg orally and 15 mg/kg rectally were evaluated in 13 Asian elephants. Blood was collected at various time points from 0 to 72 h for pharmacokinetic analysis. Pharmacokinetic parameters were determined and reached concentrations above minimum inhibitory concentrations of various bacterial organisms via both routes. A pharmacokinetic-pharmacodynamic assessment was used to estimate appropriate minimal inhibitory concentrations for bacteria that could be potentially treated with this antimicrobial. Based on these findings, levofloxacin may be a consideration for administration orally (5 mg/kg) and rectally (15 mg/kg) in Asian elephants. Antimicrobial stewardship principles, culture and susceptibility of suspected pathogens, and blood level monitoring should be used to tailor administration of levofloxacin in this species.

THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL PONAZURIL IN THE TREATMENT OF SYSTEMIC ISOSPOROSIS IN PASSERINE BIRDS.

Systemic isosporosis, previously atoxoplasmosis, is a significant cause of mortality in juvenile passerine birds. Recommended treatment regimens are empiric and vary in efficacy. The goal of this study was to determine the pharmacokinetics and pharmacodynamics of ponazuril for treatment of systemic isosporosis. Ponazuril, diluted with water to create an oral suspension (50 mg/ml), was administered (100 mg/kg) to 72 European starlings (Sturnus vulgaris) by a single dose via direct oral gavage (n = 24), a single dose injected into superworm larvae (Zophobas morio; n = 24), or a daily dose mixed with commercial dog food to top-dress feed for 5 d (n = 24). Peak plasma concentrations were 5.84, 2.46, and 9.13 µg/ml for the direct gavage, injected larvae, and top-dressed feed groups, respectively. With repeated dosing, mean plasma concentrations from the top-dressed feed group were maintained between 8.12 to 13.11 µg/ml. Results suggested ponazuril at a dosage of 100 mg/kg administered via direct gavage or top-dressed feed, but not via injected larvae, would exceed the concentrations needed to inhibit merogony of other apicomplexan parasites in cell culture (5 µg/ml). To assess the pharmacodynamics of this dose, seven passerine birds, red-vented bulbuls (Pycnonotus cafer; n = 2), blue-grey tanager (Thraupis episcopus; n = 1), and red-capped cardinals (Paroaria gularis; n = 4), were identified as shedders of systemic Isospora spp. via fecal qPCR. Birds were then treated with ponazuril (100 mg/kg) daily on top-dressed feed for 14 d. Fecal shedding was assessed via qPCR for 6 wk from the initiation of treatment. Treatment was associated with reduction in proportions of fecal shedding during the treatment period and the week following treatment, but shedding resumed in all birds by the end of sampling. Results support that treatment of breeding birds with 100 mg/kg ponazuril could reduce the shedding of active oocysts and decrease risk of clinical infection in susceptible juveniles.

Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration.

Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48 h). Drug analysis was performed by high-performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed-effects modelling, and analysis showed a peak concentration (CMAX ) of 3.8 µg/ml at 1.8 h and an elimination half-life of 9 h. The concentrations achieved were similar to what has been reported for horses and were within the half maximal effective concentration for horses for at least 10 h. A multi-dose trial in five rhinoceros receiving 2 mg/kg orally once daily for five days found mild accumulation at a predicted factor of 1.2. This study represents the first pharmacokinetic data of phenylbutazone in any rhinoceros species.

PHARMACOKINETICS OF A SINGLE DOSE OF INTRAMUSCULAR AND ORAL MELOXICAM IN YELLOW STINGRAYS (UROBATIS JAMAICENSIS).

Elasmobranchs are popular display animals in public aquaria and zoos, but medical management gaps remain in the understanding of the pharmacokinetics of analgesics and pain management in these species. Meloxicam is a nonsteroidal anti-inflammatory drug that has been evaluated intravenously and intramuscularly in teleosts, but has yet to be studied in any elasmobranch species. The pharmacokinetics of meloxicam were determined in 17 yellow stingrays (Urobatis jamaicensis). All stingrays were determined to be healthy from complete physical examinations and baseline bloodwork performed prior to study inclusion. A single dose of 1 mg/kg meloxicam intramuscularly was administered to all rays, followed by a 2 mg/kg oral dose after an 8 wk washout period. Blood samples were collected from the mesopterygial vein at baseline and nine time points up to 96 h after administration of meloxicam. Plasma concentrations were determined using reversed-phase high-performance liquid chromatography. Pharmacokinetic analysis was performed using a noncompartmental technique. The mean peak plasma concentrations for intramuscular and oral meloxicam were 1.29 and 0.42 µg/ml, respectively. The mean terminal half-lives of meloxicam after intramuscular and oral administration were 5.75 and 15.46 h, respectively. Based on these findings, the recommended meloxicam dosage and frequency for yellow stingrays is 2 mg/kg orally once daily. Due to rapid elimination with the intramuscular administration, maintaining clinically relevant plasma concentrations may be difficult using this route. Further studies are needed to determine multidose pharmacokinetics of meloxicam in yellow stingrays, as well as single-dose and multidose pharmacokinetics in other elasmobranch species.

Antimicrobial agent use in small animals what are the prescribing practices, use of PK-PD principles, and extralabel use in the United States?

In this review, the availability and deficiencies of current antimicrobial agents for companion animals in the United States are described. Although several active agents are FDA-approved for small animals, there are many unmet needs. These needs are greatest for cats, for the treatment of antibiotic drug-resistant infections, and to treat new or emerging pathogens that were not considered on older labels. The older agents approved before 1997 are often outdated, unavailable, or have inaccurate labeling. Subsequently, veterinarians treat dogs and cats with many unapproved antimicrobial agents that are licensed for human use. Although these drugs may be effective, there are also concerns that this use can produce drug-resistant bacteria that may be a public health risk. Although this concern is real, there is also evidence that any antimicrobial use in small animals can produce resistant fecal bacteria and stewardship principles should aim at reducing any unnecessary antibiotic use. This could be accomplished by avoiding some of the older, ineffective, or outdated agents described in this paper. There is a need for incentives to approve new agents that will be more appropriate for treating infections in companion animals without increasing the risk of drug-resistant bacteria that could potentially be transferred to humans and the environment and create a public health risk.

Pharmacokinetics of ketorolac in juvenile loggerhead sea turtles (Caretta caretta) after a single intramuscular injection.

Ketorolac is a non-steroidal anti-inflammatory drug administered as an analgesic in humans. It has analgesic effects comparable to opioids but without adverse effects such as respiratory depression or restrictions because of controlled drug status. We designed this study to examine the potential of ketorolac as an analgesic for sea turtle rehabilitative medicine. Our objective was to determine the pharmacokinetics of a single 0.25 mg/kg intramuscular dose of ketorolac in a population of 16 captive-raised juvenile loggerhead sea turtles (Caretta caretta). A sparse sampling protocol was utilized, and blood samples were collected for 12 hours after administration of ketorolac. Samples were analyzed with high-pressure liquid chromatography (HPLC), and a nonlinear mixed effects model (NLME) was used to determine parameters for the population. With these methods, we identified a long elimination half-life (ßT1/2  = 11.867 hr) but a low maximum concentration (CMAX  = 0.508 µg/mL) and concentrations were below the level proposed to be therapeutic in humans (EC50  = 0.1-0.3 µg/mL) for most of the collection period. We conclude that ketorolac may not be an appropriate long-term analgesic for use in loggerhead sea turtles at this dose; however, it may have some benefit as a short-term analgesic.

Cefovecin pharmacokinetics after single-dose intramuscular administration in cheetahs (Acinonyx jubatus).

Cefovecin is a third-generation cephalosporin with potential value for use in exotic felids due to its long duration of action. A sparse sampling protocol was implemented with 18 zoo-housed cheetahs (Acinonyx jubatus) to evaluate the pharmacokinetics of cefovecin (Convenia® ) after a single 8 mg/kg intramuscular injection. Blood was collected serially for 15 days following administration, and plasma cefovecin concentrations were determined using high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were estimated using population pharmacokinetic methods and non-linear mixed effects modeling (NLME). Cefovecin was well tolerated by all cats, with no adverse effects observed. Peak plasma cefovecin concentration was 84.75 µg/ml, with a mean residence time of 207.9 h and an elimination half-life of 144.1 h (6.00 days). Plasma concentrations of cefovecin were maintained >7 µg/ml in all individuals for the entire study duration (15 days). These concentrations are lower, and the half-life slightly shorter, than the values reported for domestic cats. Cefovecin was highly protein-bound (approximately 99.9%) in cheetah plasma, which is nearly identical to domestic cats. These results indicate that cefovecin is potentially useful as a long-acting antibiotic in cheetahs.

POPULATION PHARMACOKINETICS OF CEFTAZIDIME AFTER A SINGLE SUBCUTANEOUS INJECTION AND NORMAL ORAL AND CLOACAL BACTERIAL FLORA SURVEY IN EASTERN HELLBENDERS (CRYPTOBRANCHUS ALLEGANIENSIS ALLEGANIENSIS).

Population pharmacokinetics utilizing sparse sampling were used to determine pharmacokinetics of ceftazidime in eastern hellbenders (Cryptobranchus alleganiensis alleganiensis) due to their slow growth rate and the limited number of appropriately sized individuals in the zoo-housed population. Twenty-five eastern hellbenders received a single subcutaneous injection of ceftazidime at 20 mg/kg. Each animal had blood samples collected up to four times between 0 and 192 hr postinjection. Plasma samples were analyzed by high-pressure liquid chromatography. A nonlinear mixed-effects model was fitted to the data to determine typical values for population parameters, an ideal method due to the sampling limitation of each hellbender. Results indicate an elimination half-life of 36.63 hr and volume of distribution of 0.31 L/kg. Antibiotic concentrations were above a minimum inhibitory concentration (MIC) value of 8 µg/ml for 120 hr. Prior to antibiotic administration, six hellbenders had oral and six other individuals had cloacal swabs taken for aerobic culture. Fifty-five bacterial isolates were obtained (24 cloacal, 31 oral) with 10/12 (83%) individuals growing three or more different isolates and 11/12 (92%) growing Shewanella putrefaciens. Twelve isolates had susceptibility testing performed and all were susceptible to ceftazidime. These results indicate that ceftazidime is an appropriate choice of antibiotic in hellbenders and when given at a dosage of 20 mg/kg subcutaneously, maintains concentrations above the MIC of susceptible bacteria for up to 5 days.

PHARMACOKINETICS OF SUBCUTANEOUS ALPHA LIPOIC ACID, A PROPOSED THERAPEUTIC AID FOR DOMOIC ACID INTOXICATION IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

Domoic acid (DA) is a potent neurotoxin produced by certain marine algae that can cause neurologic and cardiac dysfunction by activating glutamate receptors. Glutamate receptor overexcitation results in continuous cellular activation, oxidative damage, and cell death. DA toxicosis causes disorientation and seizures, and antiseizure medications are the primary treatment. Alpha lipoic acid (ALA), a powerful antioxidant and glutathione precursor widely used in humans and dogs, can cross the blood-brain barrier to provide antioxidant availability to brain tissue. Hundreds of stranded California sea lions (CSL; Zalophus californianus) are diagnosed annually with DA toxicosis and thus are an appropriate animal in which to establish ALA dosing recommendations for treatment. The objective of this study was to determine the population pharmacokinetics of a single 10- or 20-mg/kg dose of ALA administered subcutaneously into the interscapular region to healthy rehabilitated CSL. Blood was collected at two time points between 15 min and 24 h after administration. Serum ALA concentrations were measured by liquid chromatography-mass spectrometry, and parameters were evaluated using a nonlinear mixed effects model. ALA was rapidly absorbed for each dose, peaking within 20 to 30 minutes, and t1/2 of 40 and 32 min (10 and 20 mg/kg, respectively), followed by an initial steep distribution phase and prolonged elimination phase. Peak concentration (CMAX) was 1,243 ng/ml (10-mg/ml dose) and 5,010 ng/ml (20-mg/ml dose). Serum from 13 CSLd with DA toxicosis treated with 10 mg/kg ALA for 1 to 9 d had measurable levels, and ALA was also measurable in cerebrospinal fluid from two treated CSLs. Therapeutic effects are noted with a CMAX of 4,000 to 5,000 ng/ml in humans; thus in CSLs, 20 mg/kg administered subcutaneously once daily may be sufficient to achieve a therapeutic level in this species. Determination of efficacy and optimal dosing interval and duration require additional investigation.

PHARMACOKINETICS OF A SINGLE ORAL DOSE OF PONAZURIL IN THE INDIAN PEAFOWL (PAVO CRISTATUS).

Ponazuril, a novel coccidiocidal triazinetrione, has shown promise in addressing apicomplexan diseases in mammals and birds. This study describes the pharmacokinetics of ponazuril in healthy adult Indian peafowl (Pavo cristatus) following a single oral dose administered at two different dosages. Peafowl (four males and four females) were administered compounded ponazuril at 20 or 40 mg/kg orally in a double crossover design, with a 2-wk washout period. Blood was collected from each bird at 2, 4, 8, 24, 48, 72, 96, and 120 h after administration for plasma concentration of ponazuril using high-pressure liquid chromatography. Fecals were evaluated for coccidial shedding for 3 consecutive d prior to the ponazuril trial, 1 wk after the first dose of ponazuril, and 1 wk after the second dose of the trial. After the first trial, one peafowl administered 20 mg/kg ponazuril was shedding coccidia, but no coccidia were detected by the end of the second trial. Ponazuril reached peak concentrations (Tmax) at 21.38 h + 5.25 and 22.04 h + 7.39, and peak concentration (Cmax) were 11.82 µg/ml + 3.01 and 18.42 µg/ml + 4.13, for 20 and 40 mg/kg doses, respectively. Ponazuril was detected at 120 h with a concentration of 9.48 µg/ml + 2.59 and 12.25 µg/ml + 2.89 and a half-life of 219.4 + 58.7 h and 186.7 + 58.7 h, for and 40 mg/kg doses, respectively. Ponazuril in peafowl was well absorbed orally, plasma concentrations increased with dose, and elimination was slower than current dosages for birds would suggest. No obvious adverse effects were observed at either dosage.

SAFETY OF MULTIPLE-DOSE INTRAMUSCULAR KETOPROFEN TREATMENT IN LOGGERHEAD TURTLES (CARETTA CARETTA).

Sea turtles are frequently presented for rehabilitation with injuries for which analgesic treatment is warranted. Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical veterinary medicine for musculoskeletal pain relief. Pharmacokinetics of 2 mg/kg IM have been studied in loggerhead sea turtles (Caretta caretta) as a single and a repeated dose q24hr for 3 days. Safety of longer term administration has not been performed, however, and NSAID use carries a risk of potential complications, including gastrointestinal ulceration, kidney damage, and bleeding. The objective of the current study was to determine the effects of a 5-day course of ketoprofen on thromboelastography (TEG) and hematological (including thrombocytes) and plasma biochemical analytes in loggerheads. A secondary objective was to determine 24-hr trough concentrations of ketoprofen after 5 days of treatment. Eight loggerheads were treated with ketoprofen 2 mg/kg IM q24hr for 5 days, and TEG, hematology, and plasma biochemistry panels were performed before and at the conclusion of treatment. Eight controls were treated with an equivalent volume of saline intramuscularly. Virtually no changes were detected before and after treatment or between treatment and control groups in any of the 24 endpoints evaluated, and marginal differences were not considered clinically relevant. Plasma ketoprofen concentrations after 5 days of treatment indicated no accumulation over that duration. Ketoprofen at 2 mg/kg IM q24hr for up to 5 days in loggerheads appears safe with respect to blood clotting and blood data, although other potential effects were not evaluated.

CEFOVECIN PROTEIN BINDING AS A PREDICTOR FOR EXTENDED DURATION OF ACTION: A REVIEW OF CURRENT LITERATURE AND IN VITRO ANALYSIS IN MULTIPLE ZOOLOGICAL SPECIES.

Cefovecin is a third-generation cephalosporin antibiotic with an efficacy of 2 wk following a single injection in domestic dogs and cats. A high degree of plasma protein binding to cefovecin has been proposed as one of the mechanisms responsible for the long elimination half-life, but protein binding has not been evaluated extensively in nondomestic species. In this study, a review of the current literature was conducted, and pharmacokinetic data were compiled for species in which cefovecin has been evaluated thus far. Additionally, in vitro cefovecin protein binding was evaluated in plasma from 22 nondomestic species representing a broad range of taxa. Animals of the order Carnivora demonstrated protein-binding levels of >98%, which is supportive of the long elimination half-life seen in related species. Protein binding was highly variable in Artiodactyl and Perissodactyl species, with dolphins (Tursiops truncatus) and barasingha (Rucervus duvaucelii) displaying high protein binding (99.12% to >99%), but not gazelles (Eudorcas thomsonii) or equids (91.76-92.70%). Cefovecin was not highly bound in any reptiles or birds, corresponding to short half-lives reported for these taxa. These results suggest that a high percentage of plasma protein binding in vitro may predict in which species cefovecin may exhibit a long half-life and duration of action in vivo. These findings may aid in selecting species for cefovecin pharmacokinetic research and for empirical treatment of infections caused by susceptible bacteria.

Plasma concentrations of itraconazole following a single oral dose in juvenile California sea lions (Zalophus californianus).

The objective of this study was to establish a single-dose pharmacokinetic profile for orally administered itraconazole in California sea lions (Zalophus californianus). Twenty healthy rehabilitated juvenile California sea lions were included in this study. Itraconazole capsules were administered orally with food at a target dose of 5-10 mg/kg. Blood samples were collected from each animal at 0 hr and at two of the following timepoints: 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hr. Quantitative analysis of itraconazole in plasma samples was performed by high-performance liquid chromatography. An average maximum concentration of 0.22 µg/ml ± 0.11 was detected 4 hr after administration. The average concentration fell to 0.12 µg/ml ± 0.11 by 6 hr and 0.02 µg/ml ± 0.02 at 12 hr. At no point did concentrations reach 0.5 µg/ml, the concentration commonly accepted for therapeutic efficacy. While this formulation was well tolerated by the sea lions, oral absorption was poor and highly variable among individuals. These data indicate that a single oral dose of itraconazole given as a capsule at 5-10 mg/kg, under the conditions used in this study, does not achieve therapeutic plasma concentrations in California sea lions.

Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in clinically diseased or injured Eastern box turtles (Terrapene carolina carolina), yellow-bellied sliders (Trachemys scripta scripta), and river cooters (Pseudemys concinna).

Enrofloxacin is frequently administered to turtles in wildlife clinics during rehabilitation due to its wide spectrum of antibacterial activity and availability of injectable formulations. However, sufficient pharmacokinetic data to guide dosing are lacking. The objective of this study was to determine pharmacokinetic parameters of enrofloxacin and its active metabolite, ciprofloxacin, in chelonians presenting injured to a wildlife clinic. Thirty-six Eastern box turtles (EBT, Terrapene carolina carolina), 23 yellow-bellied sliders (YBS, Trachemys scripta scripta), and 13 river cooters (RC, Pseudemys concinna) received a single subcutaneous injection of enrofloxacin at 10 mg/kg. Blood samples were collected between 0 and 240 hr postinjection. Pharmacokinetic parameters were determined using nonlinear mixed-effects modeling (NMLE). Overall elimination half-life (T½) was over 75 hr, and varied among species. T½ was 63 hr in EBT and 79 hr in YBS, which is longer than in previous reports. The volume of distribution (steady-state) was 1.4 L/kg across turtle species, but highly variable-ranging from 0.4 L/kg in RC to 1.9 L/kg in YBS. Antibiotic concentrations were above a minimum inhibitory concentration value of 0.5 µg/ml for over 200 hr. These results indicate variable pharmacokinetic parameters for enrofloxacin among turtle species, which will help guide appropriate dosing protocols in injured turtles.

Effect of diphenhydramine and cetirizine on immediate and late-phase cutaneous allergic reactions in healthy dogs: a randomized, double-blinded crossover study.

BACKGROUND: Currently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs. HYPOTHESIS/OBJECTIVE: To determine and compare the effects oral of DPH and cetirizine on the immediate- and late-phase cutaneous allergic reactions in healthy dogs. ANIMALS: Twelve healthy laboratory beagle dogs. METHODS AND MATERIALS: The study was designed as a randomized, double-blinded crossover study in which each dog served as its own control; twice-daily oral DPH (2.2 mg/kg) or cetirizine (2 mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10 days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10 days after last medication dosage. Global wheal scores (GWS) at 20 min and late-phase reactions (LPR) at 6 h post-injection were evaluated by an investigator blinded to the drug and the interventions. RESULTS: Treatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study. CONCLUSION AND CLINICAL SIGNIFICANCE: In conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.

PHARMACOKINETICS OF A SINGLE DOSE OF FLURALANER ADMINISTERED ORALLY TO AMERICAN BLACK BEARS (URSUS AMERICANUS).

Sarcoptic mange continues to impact free-ranging mammal populations, including the American black bear (Ursus americanus). Administration of a single oral dose of fluralaner may be a viable treatment option for captive and free-ranging black bears affected by mange. This novel ectoparasitic in the isoxazoline class acts as an inhibitor of γ-aminobutyric acid (GABA)-gated chloride channels and l-glutamate-gated chloride channels (GluCls) and is commercially available in the United States as a flea and tick preventative medication for domestic dogs and cats. Pharmacokinetic parameters of fluralaner were evaluated in clinically healthy American black bear cubs (n = 10) administered a single oral dose of fluralaner at a targeted minimum dose of 25 mg/kg. Blood was collected at 24 hr and 7, 14, 21, 28, 35, 42, 49, 56, 63, and 70 days, and harvested plasma was analyzed for drug concentration using high-performance liquid chromatography. The average half-life (Ke t1/2) was determined to be 4.9 days, which is shorter than that published in domestic dogs. It was estimated that the average drug withdrawal time is approximately 64-72 days in this species.