Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp. following topical administration in yaks

The plasma pharmacokinetics and mammary excretion of eprinomectin were determined in dairy yaks following topical administration at a dose of 0.5 mg/kg. The kinetics of plasma and milk concentrations were analyzed using a noncompartmental model. Plasma and milk concentrations of eprinomectin increased to reach maximal concentrations of 5.45 ± 2.84 and 2.29 ± 0.90 ng/mL at a T_max of 1.79 ± 0.57 and 2.00 ± 0.82 days, respectively. The concentration of eprinomectin in plasma was remained >0.5 ng/mL for more than 30 days after administration. The mean residence times of eprinomectin in plasma and milk were 14.73 ± 6.22 and 9.37 ± 2.81 days, respectively. The AUC value in plasma (55.89 ± 18.16 ng day/mL) was threefold greater than that in milk (18.02 ± 6.48 ng day/mL). The AUC milk/plasma ratio was 0.33 ± 0.08. The systemic availability of eprinomectin in yaks was lower than that observed value in other domestic bovines. The low level of eprinomectin excretion in milk suggests that eprinomectin can be used in yaks with zero milk‐withdrawal time. The efficacy of eprinomectin against naturally acquired larvae of Hypoderma spp. was also determined in yaks. Topically administrated eprinomectin at a dose of 0.5 mg/kg was 100% efficacious against larvae of Hypoderma bovis, H. lineatum, and H. sinense.     

Pharmacokinetics of Eprinomectin in Plasma and Milk following Subcutaneous Administration to Lactating Dairy Cattle

Eprinomectin is only available as a topically applied anthelmintic for dairy cattle. To determine whether eprinomectin can be applied as an injectable formulation in dairy cattle, a novel injectable formulation was developed and was subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/ kg. Plasma and milk samples were collected. The concentrations of eprinomectin in all samples were determined by HPLC. The peak plasma concentration (C_max)of 44.0±24.2 ng/ml occurred 39±19.3 h after subcutaneous administration, equivalent to the C_max (43.76±18.23 ng/ml) previously reported for dairy cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under the plasma concentration–time curve (AUC) after subcutaneous administration was 7354±1861 (ng h)/ml, higher than that obtained after pour-on delivery (5737.68±412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma was 211±55.2 h. Eprinomectin was detected in the milk at the second sampling time. The concentration of drug in milk was parallel to that in plasma, with a milk to plasma ratio of 0.16±0.01. The highest detected concentration of eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food Additives in 2000. The amount of eprinomectin recovered in the milk during this trial was 0.39%±0.08% of the total administered dose. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and a lower dose than a pour-on application, and that an injectable formulation of eprinomectin may be applied in dairy cattle with a zero withdrawal period.     

No detectable carotenoid concentrations in serum of llamas and alpacas

Carotenoids are lipid‐soluble pigments and important for a variety of physiological functions. They are major dietary vitamin A precursors and act as lipophilic antioxidants in a variety of tissues and are associated with important health benefits in humans and animals. All animals must acquire carotenoids from their diet, but to our knowledge, there are no studies investigating the intestinal carotenoid absorption and their blood concentrations in New World camelids. The present study aimed to assess the serum concentrations of selected carotenoids in llamas (n = 13) and alpacas (n = 27). Serum carotenoids as well as retinol (vitamin A) and α‐tocopherol (vitamin E) were determined by high‐performance liquid chromatography coupled with mass spectrometry and these were unable to detect any carotenoids (α‐ and β‐carotene, α‐ and β‐cryptoxanthin, lutein, zeaxanthin, lycopene) in the samples. The concentrations of retinol in alpacas (2.89 ± 1.13 μmol/l; mean ± SD) were higher (p = 0.024) than those found in llamas (2.05 ± 0.87 μmol/l); however, the concentrations of α‐tocopherol were not significantly (p = 0.166) different (llamas: 3.98 ± 1.83 μmol/l; alpacas: 4.95 ± 2.14 μmol/l). The results show that both llamas and alpacas are not able to absorb intact carotenoids, but efficiently convert provitamin A carotenoids to retinol.     

Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection

Holmes, K., Bedenice, D., Papich, M. G. Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection. J. vet. Pharmacol. Therap.  35 , 382–388. A single dose of florfenicol (Nuflor^®) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross‐over design, and 28‐day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long‐term effects. Maximum plasma florfenicol concentrations (C_max, measured via high‐performance liquid chromatography) were achieved rapidly, leading to a higher C_max of 4.31 ± 3.03 μg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (C_max: 1.95 ± 0.94 μg/mL). Multiple s.c. dosing at 48 h intervals achieved a C_max of 4.48 ± 1.28 μg/mL at steady state. The area under the curve and terminal elimination half‐lives were 51.83 ± 11.72 μg/mL·h and 17.59 ± 11.69 h after single 20 mg/kg i.m. dose, as well as 99.78 ± 23.58 μg/mL·h and 99.67 ± 59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL, P < 0.0001), globulin (2.76 vs. 2.16 g/dL, P < 0.0003), albumin (3.61 vs. 3.48 g/dL, P = 0.0038), white blood cell count (11.89 vs. 9.66 × 10³/μL, P < 0.044), and hematocrit (27.25 vs. 24.88%, P < 0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.     

Sarcoptic mange in three alpacas treated successfully with amitraz

Sarcoptic mange is a serious skin disease in alpacas that can result in high morbidity and even mortality. Three alpacas were presented with sarcoptic mange that had previously failed to respond to repeated topical applications of eprinomectin, and an injection of doramectin. They were moderately to severely pruritic, had extensive lesions of alopecia, erythema, scaling and crusting, and had lost weight. As no drug is currently licensed for the treatment of sarcoptic mange in alpacas in the UK, they were treated with a topical solution of amitraz (50 mL in 10 L) after initial bathing with antibacterial or keratolytic shampoos. The clinical signs completely resolved with no relapse over a 10-month follow-up period. In this small group of alpacas, amitraz was an effective and well-tolerated treatment for sarcoptic mange.     

Pharmacokinetics of intravenous gentamicin in healthy young‐adult compared to aged alpacas

The study objective was to evaluate the effects of age on aminoglycoside pharmacokinetics in eight young‐adult (<4 years) and eight aged (≥14 years) healthy alpacas, receiving a single 6.6 mg/kg intravenous gentamicin injection. Heparinized plasma samples were obtained at designated time points following drug administration and frozen at ?80°C until assayed by a validated immunoassay (QMS ^®). Compartmental and noncompartmental analyses of gentamicin plasma concentrations versus time were performed using WinNonlin (v6.4) software. Baseline physical and hematological parameters were not significantly different between young and old animals with the exception of sex. Data were best fitted to a two‐compartment pharmacokinetic model. The peak drug concentration at 30 min after dosing (23.8 ± 2.1 vs. 26.1 ± 2 μg/ml, p = .043 ) and area under the curve (70.4 ± 10.5 vs. 90.4 ± 17.6 μg hr/ml, p = .015 ) were significantly lower in young‐adult compared to aged alpacas. Accordingly, young alpacas had a significantly greater systemic clearance than older animals (95.5 ± 14.4 and 75.6 ± 16.1 ml hr^?1 kg^?1; p = .018 ), respectively). In conclusion, a single 6.6 mg/kg intravenous gentamicin injection achieves target blood concentrations of >10 times the MIC of gentamicin‐susceptible pathogens with MIC levels ≤2 μg/ml, in both young‐adult and geriatric alpacas. However, the observed reduction in gentamicin clearance in aged alpacas may increase their risk for gentamicin‐related adverse drug reactions.     

Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos)

Dechant, J. E., Rowe, J. D., Byrne, B. A., Wetzlich, S. E., Kieu, H. T., Tell, L. A. Pharmacokinetics of ceftiofur crystalline free acid after single and multiple subcutaneous administrations in healthy alpacas (Vicugna pacos). J. vet. Pharmacol. Therap.  36 , 122–129. Six adult male alpacas received one subcutaneous administration of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. After a washout period, the same alpacas received three subcutaneous doses of 6.6 mg/kg CCFA at 5‐day intervals. Blood samples collected from the jugular vein before and at multiple time points after each CCFA administration were assayed for ceftiofur‐ and desfuroylceftiofur‐related metabolite concentrations using high‐performance liquid chromatography. Pharmacokinetic disposition of CCFA was analyzed by a noncompartmental approach. Mean pharmacokinetic parameters (±SD) following single‐dose administration of CCFA were C_max (2.7 ± 0.9 μg/mL); T_max (36 ± 0 h); area under the curve AUC_0→∞ (199.2 ± 42.1 μg·h/mL); terminal phase rate constant λz (0.02 ± 0.003/h); and terminal phase rate constant half‐life t_1/2λz (44.7 h; harmonic). Mean terminal pharmacokinetic parameters (±SD) following three administrations of CCFA were C_max (2.0 ± 0.4 μg/mL); T_max (17.3 ± 16.3 h); AUC_0→∞ (216.8 ± 84.5 μg·h/mL); λz (0.01 ± 0.003/h); and t_1/2λz (65.9 h; harmonic). The terminal phase rate constant and the T_max were significantly different between single and multiple administrations. Local reactions were noted in two alpacas following multiple CCFA administrations.     

Pharmacokinetics of intrarectal omeprazole in alpacas

Marmulak, T., Stanley, S., Kass, P.H., Wiebe, V., McKemie, D., Pusterla, N. Pharmacokinetics of intrarectal omeprazole in alpacas. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.00149.x. The purpose of this study was to evaluate the pharmacokinetics of omeprazole in three different vehicles when administered rectally to six alpacas. Alpacas were given single doses of omeprazole (4 mg/kg) in a double‐blinded, randomized cross‐over design with a 1 week washout period. Omeprazole formulations consisted of (1) Treatment A: omeprazole paste mixed in surgical lubricant (2) Treatment B: omeprazole capsule contents in 8.4% sodium bicarbonate and (3) Treatment C: omeprazole capsule contents in surgical lubricant and 8.4% sodium bicarbonate solution. Plasma samples were drawn at 0, 5, 10, 15, 30, 45, 60, 90, 120, 180, 300 and 480 min. Omeprazole plasma concentrations were determined by high‐pressure liquid chromatography‐mass spectrometry. Pharmacokinetic results demonstrated median peak plasma concentrations (C_max) of 7.35 (3.2–15.2), 7.30 (1.7–10.9) and 8.65 (1.8–19.3) ng/mL and median area under the concentration curve (AUC_(0–180)) of 747 (237–1681) min·ng/mL, 552.9 (39–1063) min·ng/mL, and 972 (107–1841) min·ng/mL for treatments A, B and C, respectively. The median half‐lives were similar between groups: 38, 50, and 53 min. As a result of the low measured omeprazole plasma concentrations, it is assumed that rectal absorption of omeprazole is poor in alpacas and not an effective route of administration.     

Measurement of cardiac troponin I utilizing a point of care analyzer in healthy alpacas

Background

Myocardial disease in camelids is poorly characterized. Nutritional (selenium deficiency) and toxic (ionophore toxicity) myocardial disease have been reported in camelids. Diagnosis and management of these and other myocardial diseases might be enhanced by evaluating cardiac troponin I (cTnI) concentrations. No information about cTnI reference intervals in camelids is currently available.

Hypothesis/Objectives

(A) To determine cTnI concentrations obtained using a point of care i-STAT^®1 analyzer (Heska Corporation) in healthy alpacas; (B) to compare alpaca cTnI concentrations between heparinized whole blood and plasma samples and between 2 different storage conditions (4 °C for 24 h or −80 °C for 30 days); (C) to examine assay reproducibility using the i-STAT^®1.

Animals, materials and methods

23 healthy alpacas were evaluated. Blood and plasma samples were analyzed by the i-STAT^®1 within 1 h of collection. Aliquots of plasma were stored at either 4 °C for 24 h or −80 °C for 30 days, and then analyzed. Assay reproducibility was determined by comparing 2 plasma or whole blood cTnI concentrations measured on the same sample over a 10 min period.

Results

Analyzer-specific plasma cTnI concentrations in clinically normal alpacas had a median of <0.02 ng/mL (range: <0.02 ng/mL to 0.07 ng/mL). Plasma and whole blood concentrations showed good agreement. Storage did not affect cTnI concentrations (p > 0.75). Plasma cTnI concentrations had coefficient of repeatability of 0.02 ng/mL.

Conclusions

The i-STAT^®1 can measure cTnI in alpacas on both plasma and whole blood and provides similar values for both samples. Storage at 4 °C for 24 h or −80 °C for 30 days does not affect estimates of plasma cTnI. Evaluation of cTnI might be of value in assessing cardiac disease in this species.     

Pharmacokinetics of subcutaneously administered doramectin in alpacas

The objective of this research was to evaluate comparative pharmacokinetics of doramectin in alpacas, after subcutaneous administration of 0.2 mg/kg dose. Six healthy adult alpacas, mean age of 5 years ± 1, (three female and three gelded males) of mean bodyweight of 62 kg ± 16 kg with an average body condition scored 2.8 ± 1 out of five, were used in this study. Serial blood samples were collected from the jugular vein before the administration until day 21 afterwards to establish the pharmacokinetics of doramectin after its subcutaneous administration at 0.2 mg/kg dose. The blood samples were analysed using high-performance liquid chromatography (HPLC), fluorescence detection method with precolumn derivatisation, validated for alpacas. The pharmacokinetic parameters were calculated using a noncompartmental model, and results showed Cmax (6.05 ± 5.34 ng/ml), Tmax (3.83 ± 2.48 days), AUC (62.12 ± 18.86 ng/ml × d), terminal half-life (6.2 ± 4.9 days) and MRT (11.56 ± 4.43 days). The results of this study showed that the Cmax and AUC were much lower than in cattle and sheep at the same dosage. Tmax remained similar to cattle and sheep. This study presents valuable information about pharmacokinetics of doramectin in alpacas, which can be utilised in its future efficacy studies.     

Pharmacokinetics of meloxicam in mature swine after intravenous and oral administration

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross‐over design. Plasma samples collected up to 48 h postadministration were analyzed by high‐pressure liquid chromatography and mass spectrometry (HPLC‐MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (C_MAX) after p.o. administration was 1070 ng/mL (645–1749 ng/mL). T_MAX was recorded at 2.40 h (0.50–12.00 h) after p.o. administration. Half‐life (T½ λ_z) for i.v. and p.o. administration was 6.15 h (4.39–7.79 h) and 6.83 h (5.18–9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39–351%). The results of this study suggest that meloxicam is well absorbed after oral administration.     

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of tulathromycin were as follows: C_max (121.54 ± 19.01 ng/mL); T_max (12 ± 12–24 h); area under the curve AUC_0→∞ (8324.54 ± 1706.56 ng·h/mL); terminal‐phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal‐phase rate constant half‐life t_1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: C_max (1594 ± 379.23 ng/mL); T_max (12 ± 12–36 h); AUC_0→∞ (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t_1/2λz (155.28 h; harmonic). All goats had injection‐site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.     

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

The aim of this study was to determine the pharmacokinetics and prostaglandin E₂ (PGE₂) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E₂ concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE₂ concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t_1/2λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg^?1 hr^?1 (range, 55.45–179.3 ml kg^?1 hr^?1). The mean C_max, T_max and t_1/2λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000–34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC₈₀) of PGE₂ by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE₂ identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.     

Cardiovascular effects of butorphanol in isoflurane-anesthetized alpacas

Butorphanol has been used clinically to provide analgesia in alpacas, but cardiovascular effects have not been reported. Using a randomized cross‐over design, eight healthy, young adult female alpacas (3 ± 1 SD years) weighing 64 ± 9 SD kg were anesthetized with isoflurane by mask followed by tracheal intubation and maintenance of anesthesia with 1.75% et (isoflurane) in oxygen. Two treatments, butorphanol (0.1 mg kg^–1 IV) and control (saline, IV) were assigned to the animals in a randomized manner allowing a minimum of two weeks between treatments. While anesthetized, animals were instrumented for measurement of cardiovascular variables including systolic, diastolic, and mean arterial blood pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output (CO) and pulmonary temperature (TEMP). CO was measured via thermodilution using 5 mL of iced 5% dextrose and recording the average of three replicate measurements. Cardiac index, systemic vascular resistance (SVR) and pulmonary vascular resistance were also calculated. Arterial and mixed venous blood samples were collected for blood gas analysis [pH, pO₂, pCO₂, (HCO₃^?), BE, Hb_sat]. Variables were collected at baseline (time 0) and at 5, 10, 15, 30, 45, and 60 minutes following injection. Variables were analyzed by anova for repeated measures with post‐hoc differences between means identified using the Bonferroni comparison (p < 0.05). SVR decreased five minutes after administration of butorphanol (Huynh Feldt corrected p = 0.045) and remained decreased for 60 minutes. TEMP decreased with time in both groups (Huynh Feldt corrected p = 0.000027), but groups were not different between each other. Other cardiovascular and blood gas variables were not different between groups. We conclude that butorphanol (0.1 mg kg^–1 IV) had minimal effects on the cardiovascular system of these alpacas, causing a mild decrease in SVR.     

The influence of Actinobacillus pleuropneumoniae infection on tulathromycin pharmacokinetics and lung tissue disposition in pigs

A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)‐infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high‐performance liquid chromatography with tandem mass spectrometry (LC‐MS/MS) method. The mean maximum plasma concentration (C_max) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for C_max of tulathromycin in infected pigs was 386 ± 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 ± 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 ± 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half‐life t_1/2el = 126 h in plasma and t_1/2el = 165 h in lung, as well as longer drug persistent in infected pigs, was found.     

Factors associated with low vitamin D status of Australian alpacas

Objective To investigate factors associated with low vitamin D status of alpacas at pasture in southern Australia. Design A 2‐year survey of alpacas from two farms in South Australia and three in Victoria. Blood samples were collected from 20 to 30 alpacas on each farm on five occasions each year. Breed, gender, age and fleece colour of animals were recorded. Method Blood samples were assayed for plasma 2.5‐hydroxycholecalciferol (25‐OH D₃) and plasma inorganic phosphorus (Pi). Data sets from 802 animal samples were analysed by multiple regression to determine variables associated with low vitamin D status of alpacas. The relationship between plasma 25‐OH D₃ and plasma Pi was also investigated. Results Vitamin D status was significantly affected by month of sampling, with low values in late winter and high values in summer. Plasma vitamin D concentrations increased with age, were higher in alpacas with light fleeces than in those with dark fleeces and were also higher in the Suri than in the Huacaya breed. Plasma Pi concentrations were generally lower in alpacas with plasma 25‐OH D₃ values < 25 nmol/L. Conclusions Young alpacas with dark fleeces are most at risk from vitamin D insufficiency in late winter in southern Australia. The present study indicates that plasma Pi values are not a reliable indicator of vitamin D status of alpacas as assessed by plasma 25‐OH D₃ concentrations.     

The treatment of bovine sarcoptic mange (Sarcoptes scabiei var. bovis) using eprinomectin extended-release injection

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated in cattle harbouring induced infestations of Sarcoptes scabiei var. bovis (sarcoptic mange) in three studies conducted in Germany (two studies) and Austria (one study). A total of 44 cattle were included in the studies, 12 in one study and 16 in each of the other two studies. Approximately eight weeks following initial induced infestation, cattle in each study were formed into replicates of two animals each on the basis of pre-treatment bodyweights. Within replicates the animals were randomly allocated to one of two treatments: ERI vehicle (control) or Eprinomectin 5% (w/v) ERI (1.0 mg eprinomectin/kg). Treatments were administered at 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder once on day 0. The number of live mites in skin scrapings was determined prior to treatment and at weekly intervals for eight weeks after treatment. Severity of skin lesions was evaluated and scored when skin scrapings were taken. In all studies, animals were weighed before infestation and again prior to and at 56 days after treatment.     

Exenatide dosing in alpacas

In order to investigate whether exenatide could be used to stimulate glucose clearance and insulin secretion in alpacas without causing colic signs, six healthy adult alpacas were injected once a day with increasing subcutaneous doses. A follow‐up intravenous glucose injection was given to induce hyperglycemia, and serial blood samples were collected to measure plasma concentrations of glucose, insulin, triglycerides, beta‐hydroxybutyrate, and nonesterified fatty acids. The exenatide doses used were saline control (no drug), and 0.02, 0.05, or 0.1 mcg/kg injected subcutaneously. Alpacas had significantly lower plasma glucose concentrations and higher insulin concentrations on all treatment days compared with the control day, but the increase in insulin was significantly greater and lasted significantly longer when the alpacas received the two higher dosages. Two of the alpacas developed mild colic signs at the 0.05 mcg/kg dose and were not evaluated at the highest dose. Based on these findings, the 0.05 mcg/kg dose appears to offer the greatest stimulation of insulin secretion and glucose clearance without excessive risk or severity of complications.     

Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin

The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and C_MAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No‐Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated.     

Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration

The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297–392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC–MS–MS methods. The mean (± SD) C_max, C_min, and C_average plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam‐treated calves will have low residue concentrations by 21 days after repeated oral administration.