Cestodiasis with intestinal diverticulosis in a lesser flamingo (Phoeniconaias minor).

An adult female lesser flamingo (Phoeniconaias minor), caught in the African Rift Valley in 1991 and subsequently housed at the Baltimore Zoo, died of severe visceral gout in 1996. Necropsy revealed a white, moderately firm, nodular lesion, 1 cm in diameter, in the serosal wall of the small intestine. Although it was initially thought to be a tumor or focal granuloma, histologic examination revealed multiple cestodes deeply embedded at the base of the crypts between the intestinal villi, with their massive scolices (up to 3.4 mm in diameter) distending these spaces into multiple diverticulae. The mucosal epithelium surrounding the scolices was severely attenuated. Around the diverticulae, in the submucosa and muscularis, was a mild to moderate lymphocytic reaction and mild fibrosis. The proximity of multiple scolices and extensive invasion of host tissue suggested that the infection occupied a preexisting lesion. The cestodes were cyclophyllids but were distinct from any species previously reported from flamingos. Helminths should be included in differential diagnoses for gastrointestinal nodules in flamingos.     

Terbinafine pharmacokinetics after single dose oral administration in the dog

Terbinafine is an allylamine antifungal prescribed for the treatment of mycoses in humans. It is increasingly being used in veterinary patients. The purpose of this study was to evaluate the pharmacokinetic properties of terbinafine in dogs after a single oral dose. Ten healthy adult dogs were included in the study. A single dose of terbinafine (30–35 mg/kg) was administered orally, and blood samples were periodically collected over a 24 h period during which dogs were monitored for adverse effects. Two of 10 dogs developed transient ocular changes. A high‐performance liquid chromatography assay was developed and used to determine plasma terbinafine concentrations. Pharmacokinetic analysis was performed using PK Solutions^® computer software. Area under the curve (AUC) from time 0 to 24 h was 15.4 μg·h/mL (range 5–27), maximal plasma concentration (C_max) was 3.5 μg/mL (range 3–4.9 μg/mL) and time to C_max (T_max) was 3.6 h (range 2–6 h). The time above minimal inhibitory concentration (T > MIC) as well as AUC/MIC was calculated for important invasive fungal pathogens and dermatophytes. The T > MIC was 17–18 h for Blastomyces dermatitidis, Histoplasma capsulatum and dermatophytes (Microsporum spp. and Trichophyton mentagrophytes), while the MIC for Sporothrix schenckii and Coccidioides immitis was exceeded for 9.5–11 h. The AUC/MIC values ranged from 9 to 13 μg h/mL for these fungi. Our results provide evidence supporting the use of terbinafine as an oral therapeutic agent for treating systemic and subcutaneous mycoses in dogs.     

Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon)

ObjectiveTo assess the population pharmacokinetics of methadone in deer.Study designProspective non-randomized experimental trial.AnimalsTwelve healthy adult sika deer (nine males and three females).MethodsDeer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg⁻¹ or 1 mg kg⁻¹. Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM).ResultsA two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour⁻¹), metabolic clearance (34.6 L hour⁻¹), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour⁻¹), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour⁻¹, 121.0 L hour ⁻¹, 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration.Conclusions and Clinical relevanceFollowing intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer.     

Population pharmacokinetics of a single intramuscular administration of tulathromycin in adult desert tortoises (Gopherus agassizii)

Tulathromycin, a long acting macrolide antibiotic, has demonstrated efficacy against respiratory pathogens including Mycoplasma bovis and M. hyopneumoniae. A pharmacokinetic study was performed to evaluate the clinical applicability of tulathromycin in desert tortoises following a single intramuscular dose of 5 mg/kg. A single blood sample was collected from 110 different desert tortoises at 0.25, 0.5, 1, 4, 8, 24, 48, 72, 120, and 240 h following drug administration. Plasma concentrations of the parent form of tulathromycin were measured using liquid chromatography/mass spectrometry. As each tortoise was only bled once, pharmacokinetic parameters were initially estimated using a naïve pooled data approach. Given the variability in the data, population‐based compartmental modeling was also performed. Using nonparametric population compartmental modeling, a two‐compartment model with first‐order absorption and elimination best fit the data. An observed C_max of 36.2 ± 29.7 μg/mL was detected at 0.25 h (observed T_max). The elimination half‐life (T_½el) was long (77.1 h) resulting in detectable plasma concentrations 240 h postadministration. This study represents a preliminary step in evaluating the utility of tulathromycin in chelonian species and demonstrates that population data modeling offers advantages for estimating pharmacokinetic parameters where sparse data sampling occurs and there is substantial variability in the data.     

Population pharmacokinetics of ceftazidime after a single intramuscular injection in wild turtles

Ceftazidime, a third‐generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half‐life (T½) of approximately 35 hr and volume of distribution (V_SS) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild‐type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.     

单剂量氟苯尼考内服及肌注在家兔体内药代动力学研究

健康新西兰白兔20只,随机分为A、B 2组,A组内服单剂量30 mg/kg氟苯尼考试验品,B组肌注单荆量30mg/kg氟苯尼考试验品.用高效液相色谱法测定血浆中的药物浓度,3p97药代动力学程序软件处理药--时数据,A组药--时数据符合--室开放模型(W=1/C2),主要药代动力学参数T1/2Ka=(0.461±0.066)h,T1/2ke=(2.013±0.195)h,Tpeak=(1.180±0.123)h,Cmax=(7.332±1.000)mg/L,AUC=(31.445±3.566)mg·L-1·h,V/F=(2.995±0.330)L/kg;B组药-时数据也符合一室开放模型(W=1/C2),主要药代动力学参数T1/2Ka=(0.802±0.098)h,T1/2ke=(2.317±0.136)h,Tpeak=(1.805±0.103)h,Cmax=(6.646±0.578)mg/L,AUC=(38.714±3.727)mg·L-1·h,V/F=(2.772±0.303)L/kg.试验结果表明,氟苯尼考在家兔体内主要药动学特征为内服吸收迅速、分布快而广、消除较快;肌注吸收速度显著慢于内服.分布广泛,消除也较快.     

Bill impaction in a group of captive Caribbean flamingos (Phoenicopterus ruber ruber).

Flamingos are filter feeders that only rarely ingest larger food items. Their bill anatomy is adapted to the suction, filtration, and ejection of a fluid medium. This case report documents a rare case of bill impaction in a group of Caribbean flamingos (Phoenicopterus ruber) that were kept in a mixed exhibit together with roseate spoonbills (Platalea ajaja) and scarlet ibis (Eudocimus ruber). The latter species received fatty minced meat as part of their diet, which was also accessible to the flamingos. Weakness and poor body condition of one flamingo were noted. On clinical examination, the animal was emaciated, hypoglycemic, and showed a severe impaction of the bill with a mixture of lard, mud, and sand. This mixture had compressed the tongue and eventually had most likely prevented further food intake. In five additional flamingos, a bulging of the gular area, similar to the extension of this area during the tongue-retraction stage of the feeding cycle, was noted and interpreted as a sign of tongue displacement by similar masses in their bills. All animals were caught and the masses removed. All animals resumed food intake immediately, and the emaciated animal rapidly improved in condition. Food presentation was changed so that the trays for the other species were no longer accessible to the flamingos, and no similar problems have been observed since that time.     

Tolerance and pharmacokinetics of cephalexin in cats after oral administration

The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.     

Pharmacokinetics of ponazuril after administration of a single oral dose to green turtles (Chelonia mydas)

The coccidian protozoan, Caryospora cheloniae, has been associated with severe enteritis and encephalitis in immature farm-raised green turtles (Chelonia mydas) in the Cayman Islands, immature green turtles off the coast of Florida, and immature stranded sea turtles in Australia. An effective anti-coccidial drug that is both orally absorbed and well-distributed throughout the body is needed for treatment of turtles diagnosed with coccidiosis in rehabilitation facilities. Ponazuril is a triazine antiprotozoal drug that is approved in the USA for the treatment of another Apicomplexan, Sarcocystis neurona, and has also been successfully used in the therapy of other coccidian parasites. The objective of this study was to perform an oral dose-ranging pilot study (10–100 mg/kg of body weight ponazuril) in green turtles (N = 9), followed by oral administration of ponazuril at 100 mg/kg body weight (N = 8) to assess its disposition. Another goal of this study was to optimize the method of oral drug administration to green turtles. Plasma ponazuril concentrations were quantified using high performance liquid chromatography (HPLC). Standard compartmental models were fit to the data. Ponazuril was absorbed after oral administration at 100 mg/kg BW, with a maximum plasma concentration of 3.3 µg/ml. Dose-dependent pharmacokinetic parameters only weakly correlated with the dose rate, apparently due to considerable pharmacokinetic variability observed between turtles. Administration of ponazuril in gelatin capsules using a balling gun was deemed the least variable and most successful method of drug administration. Further studies are needed to evaluate the safety and efficacy of ponazuril in sea turtles with coccidiosis.     

Pharmacokinetics of florfenicol in crucian carp (Carassius auratus cuvieri) after a single intramuscular or oral administration

The pharmacokinetics of florfenicol (FF) was studied in plasma after a single dose (40 mg/kg) of intramuscular (i.m.) or oral gavage (p.o.) administration to crucian carp (Carassius auratus cuvieri) in freshwater at 25 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two-compartment open models follow both routes of administration. The estimates of total body clearance (CL(b) ), volume of distribution (V(d) /F), and absorption half-life (T(1/2(ka)) ) were 0.067 L/h/kg and 0.145 L/h/kg, 2.21 L/kg and 1.04 L/kg, 2.75 and 1.54/h following i.m. and p.o. administration, respectively. After i.m. injection, the elimination half-life (T(1/2(β)) ) was calculated to be 38.2h, the maximum plasma concentration (C(max) ) to be 16.82 μg/mL, the time to peak plasma FF concentration (T(max) ) to be 1.50 h, and the area under the plasma concentration-time curve (AUC) to be 597.4 μg/mL·h. Following p.o. administration, the corresponding estimates were 2.17 h, 29.32 μg/mL, 1.61 h, and 276.1 μg/mL·h.     

Population pharmacokinetics of marbofloxacin in aqueous humor after intravenous administration in dogs

OBJECTIVE: To evaluate, by use of population pharmacokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection. ANIMALS: 63 dogs. METHODS: Dogs received a single dose of marbofloxacin (2 mg x kg(-1), IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg x kg(-1) IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity. RESULTS: A maximum marbofloxacin concentration of 0.41 +/- 0.17 microg x mL(-1) was reached in the aqueous humor 3.5 hours after IV administration. In the post-distributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of marbofloxacin (2 mg x kg(-1), IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mg x kg(-1) would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections.     

Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose

The purpose of this study was to establish the stereospecific pharmacokinetics of ketorolac (KT) in calves following a single 2 mg/kg intravenous (i.v.) and a single 8 mg/kg oral dose. Plasma concentrations were determined using a stereoselective HPLC assay. Pharmacokinetic parameters for both the stereoisomers were estimated by model-independent methods. Following an i.v. dose, the plasma concentration profiles of the stereoisomers were similar with half-lives of 5.9 +/- 5.1 h for R-KT and 6.0 +/- 4.9 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.0470 +/- 0.0370 and 0.0480 +/- 0.0370 L/h/kg respectively. After an oral dose, the terminal half-lives were longer than following i.v. administration with values of 14.77 +/- 3.08 and 14.55 +/- 2.95 h for R-KT and S-KT respectively. The average oral bioavailability was 86.5 +/- 20.6% for R-KT and 86.7 +/- 20.3% for S-KT. The results indicate that the stereoisomers of KT have similar pharmacokinetic profiles in calves. Although, unlike humans, bioinversion between KT stereoisomers appears minimal in calves, studies with individual isomers are needed before any firm conclusions can be drawn about this lack of KT bioinversion.     

Pharmacokinetic study of enrofloxacin in Nile tilapia (Oreochromis niloticus) after a single oral administration in medicated feed

The objective of this study was to evaluate the disposition kinetics of enrofloxacin (ENR) in the plasma and its distribution in the muscle tissue of Nile tilapia (Oreochromis niloticus) after a single oral dose of 10 mg/kg body weight via medicated feed. The fish were kept at a temperature between 28 and 30 °C. The collection period was between 30 min and 120 h after administration of the drug. The samples were analyzed by high‐performance liquid chromatography with a fluorescence detector (HPLC‐FLD). The ENR was slowly absorbed and eliminated from the plasma (C_max = 1.24 ± 0.37 μg/mL; T_max = 8 h; T_1/2Ke = 19.36 h). ENR was efficiently distributed in the muscle tissue and reached maximum values (2.17 ± 0.74 μg/g) after 8 h. Its metabolite, ciprofloxacin (CIP), was detected and quantified in the plasma (0.004 ± 0.005 μg/mL) and muscle (0.01 ± 0.011 μg/g) for up to 48 h. After oral administration, the mean concentration of ENR in the plasma was well above the minimum inhibitory concentrations (MIC₅₀) for most bacteria already isolated from fish except for Streptococcus spp. This way the dose used in this study allowed for concentrations in the blood to treat the diseases of tilapia.     

Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana).

Parasitism is common in wild and captive amphibians; however, pharmacologic data are lacking for anthelmintic drugs. This study was developed to determine the plasma pharmacokinetics of selamectin after topical administration in bullfrogs. Thirty-two adult American bullfrogs (Rana catesbeiana) were randomly assigned into eight groups of four with each group representing a different collection time point. Seven groups received selamectin (6 mg/ kg) topically and the remaining group served as the untreated control group. One group of frogs was euthanized and blood samples immediately collected on days 0 (control), 1, 5, 10, 15, 20, 25, and 30. Plasma was analyzed for selamectin using high performance liquid chromatography with fluorescence detection. Individual samples were analyzed, then data were reported as the mean of the four frogs at each time point. A histologic evaluation of the lung, liver, kidney, and skin tissues was performed and none of the frogs showed histologic evidence of toxicity due to selamectin administration. The mean peak plasma concentration was 162.5 +/- 42.3 ng/ml, area under the curve was 2,856 ng day/ml, mean residence time was 12.2 days, and disappearance half-life was 1.87 days. Based on the plasma pharmacokinetics, bullfrogs appear to absorb selamectin very efficiently, concentrations reach high levels in the plasma, and there were no apparent histologic effects from single dose administration.