Pharmacokinetics and pharmacodynamics of intravenously and subcutaneously administered pantoprazole in sheep (Ovis aries).

Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.

Pharmacokinetics of nalbuphine administered intravenously and subcutaneously in goats (Capra aegagrus hircus).

The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min-1 ± SD), 17311.01 ± 7227.32 (min·ng·mL-1 ± SD), 675.6 ± 337.13 (ng·mL-1 ± SD), and 44.5 ± 13.8 (mL·min-1·kg-1 ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), and maximum plasma drug concentration were 129 ± 52.9 (min-1 ± SD), 20826.5 ± 14376.2 (min·ng·mL-1), and 368.03 ± 503.78 (ng·mL-1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.

Pharmacokinetics of oral clonazepam in growing commercial pigs (Sus scrofa domestica).

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild-to-moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse-phase high-performance liquid chromatography, and compartment models were fit to time-concentration data. A one-compartment first-order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half-life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted.

Pharmacokinetics of famotidine in goats after intravenous administration.

There is currently limited pharmacokinetic data for the use of famotidine in goats for treatment and prevention of abomasal ulceration. The objective of this study was to determine the pharmacokinetic parameters after a single intravenous administration of famotidine (0.6 mg/kg). Famotidine was administered to six healthy goats and plasma samples were collected over a 24-h period. The famotidine concentration was measured using reverse phase high-performance liquid chromatography (HPLC). Non-compartmental analysis was then used to determine the pharmacokinetic parameters. The maximum plasma concentration was estimated at 5476.68 ± 1530.51 ng/mL and elimination half-life was estimated at 18.455 ± 13.26 min. The mean residence time was determined to be 19.85 ± 12.14 min with the apparent volume of distribution being estimated at 321.924 ± 221.667. The area under the curve was determined to be 54230.08 ± 24947.6 min*ng/mL. Total exposure and elimination half-life were less than what has been reported in cattle and horses. Future research evaluating the pharmacokinetics of subcutaneous administration and looking at the pharmacodynamics of famotidine in goats is needed to determine the effectiveness of famotidine on raising pH levels of the abomasum.

Pharmacokinetics of intraarticular liposomal amphotericin B in goats (Capra aegagrus hircus).

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34-0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.

Randomized comparison between a forced air system and warm water bath for resuscitation of neonatal hypothermic calves with or without oral administration of caffeine.

BACKGROUND: Hypothermia is a cause of neonatal calf death in cold climates. Practical and effective rewarming methods are important for bovine health within affected regions. HYPOTHESIS/OBJECTIVES: To compare the rewarming rate and blood analytes (glucose, lactate, and cortisol) of calves resuscitated with forced air with warm water bath, with or without oral administration of caffeine. ANIMALS: Twenty healthy neonatal Holstein bull calves. METHODS: In this randomized, prospective study, calves born healthy and without history of dystocia were cooled to 32°C rectal temperature then thermally resuscitated using either forced air rewarming or warm water bath (40°C) with or without oral administration of caffeine. Rectal temperatures were used to quantify recovery rate. Measurements of glucose, lactate, and cortisol were recorded for every 2°C change in rectal temperature. RESULTS: Rectal temperature decline (0.03°C per minute) and total cooling time (191.0 ± 33.3 minutes) did not significantly differ among treatment groups. Calves were successfully resuscitated to 38°C by either method. Time required to euthermia using warm water was significantly faster (0.1°C per minute; 64.3 ± 17.8 minute; P < .05) than forced air (0.05°C per minute; 123.1 ± 20.0 minutes). Caffeine had no significant effect on resuscitation rate (P = .14; 95% CI, -0.002 to 0.024) in either treatment; however, caffeine was associated with reduced time to euthermia by 8.3 and 10.8 minutes, respectively. Changes in metabolic variables (glucose, lactate, and cortisol), were inversely related to rectal temperature with no statistical significance among rewarming methods. CONCLUSIONS AND CLINICAL IMPORTANCE: Although warm water submersion is faster, forced air rewarming is an effective alternative for restoration of euthermia.

Delayed Urethral Obstruction after Migration of a Ballistic Pellet in an Alpine Wether.

A one-year-old alpine wether was presented for emergency evaluation of stranguria. Diagnostics identified a moderately distended bladder and mild dehydration. Preliminary lateral radiographs identified two metallic structures consistent with projectile pellets in the pelvic and perineal regions and no evidence of radiopaque uroliths. A tube cystostomy was performed, and a contrast urethrogram revealed one of the pellets in the perineal region was in proximity to the urethral obstruction. Subsequent radiography and ultrasound identified the pellet as being within the lumen of the urethra. Examination of the trichotomized skin revealed two scars, including a scar over the paralumbar fossa in the region of the urinary bladder suggestive of a projectile injury. The pellet was removed by a perineal urethrotomy. The patient was able to spontaneously urinate after urethrotomy, passed a tube cystostomy challenge two weeks after surgery, and was discharged. No complications were reported. While uncommon in the veterinary and comparative medical literature, clinicians should consider the potential for projectile pellets to migrate into the urinary tract after initial injury.

The pharmacokinetics and pharmacodynamics of esomeprazole in sheep after intravenous dosing.

Abomasal (gastric) ulceration is a morbidity in sheep, and currently, there is a paucity of pharmacokinetic and pharmacodynamic data for gastroprotectant drugs reported for this species. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via increasing the gastric pH. The objective of this study was to report the pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single intravenous dosing. Four healthy adult Southdown cross ewes had blood collected over a 24 h time period after single intravenous dosing of esomeprazole at 1.0 mg/kg. Abomasal fluid was sampled over 24 h before and after esomeprazole administration. Plasma samples were analyzed for concentrations of esomeprazole and the esomeprazole metabolite, esomeprazole sulfone by high performance liquid chromatography. Pharmacokinetic and pharmacodynamic data were evaluated with specialized software. Esomeprazole was rapidly eliminated after IV administration. Elimination half-life, area under the curve, initial concentration (C0), and clearance were 0.2 h, 1,197 h*ng/mL, 4,321 ng/mL, and 0.83 mL/h/kg, respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16 h, 22.5 h*ng/mL, and 65.0 ng/mL, respectively. Abomasal pH was significantly elevated from 1 to 6 h after administration and remained above 4.0 for at least 8 h after administration. No adverse effects were noted in these sheep. Esomeprazole was rapidly eliminated in sheep, similar to goats. Abomasal pH was increased, but future studies will be necessary to develop a clinical management approach to the use of esomeprazole in sheep.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs.

Purpose: Describe the pharmacokinetics of extended-release parenteral ceftiofur (Excede®) in canine tear film and compare these concentrations to minimal inhibitory concentrations (MICs) of ceftiofur against common ocular pathogens in dogs. Method: Six dogs of various breeds were enrolled. Disruption of blood-tear barrier was achieved with histamine-induced conjunctivitis to ensure clinical relevance of the results. Each dog received a single subcutaneous injection of 5 mg/kg Excede®, followed by tear collection with Schirmer strips at times 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 h. Drug quantification was performed with liquid chromatography-mass spectrometry. MICs were determined for Staphylococcus pseudintermedius, Streptococcus canis and Pseudomonas aeruginosa by assessing bacterial growth (n = 10 per bacterial species) in the presence of ceftiofur at increasing concentrations. Results: Blood-tear barrier breakdown provided tear film concentrations of ceftiofur 3.2-28.9-fold higher than in the contralateral healthy eye (n = 1 dog, pilot experiment). In all six dogs, ceftiofur concentrations in tears varied from 2.3 to 637.5 ng/mL and were detectable up to 10 days (240 h) after subcutaneous injection. However, tear levels always remained below MICs for common ocular isolates (≥640 ng/mL). Conclusions: Ceftiofur reached the tear compartment (for up to 10 days) after a single parenteral injection, however tear concentrations were extremely variable and too low to be effective against common bacterial pathogens in dogs. Further studies with different ceftiofur dosage or other long-acting injectable antibiotics are warranted.

Ultrasonography and digital radiography findings in sheep with clinical disease associated with small ruminant lentivirus infection.

Digital radiography and ultrasonographic images were used in this case series to evaluate 4 ewes from a single flock for chronic weight loss and ill-thrift. On examination, all displayed tachypnea, dyspnea, coughing, and normothermia with abnormal thoracic auscultations. Three of the 4 animals were diagnosed with chronic respiratory disease associated with Maedi-visna (MV) infection confirmed via serologic testing. Diagnostic thoracic imaging identified characteristics consistent with pathological lesions associated with interstitial pneumonia in the 3 MV affected animals; these findings were absent in the animal that tested negative for MV. Key clinical message: Diagnostic imaging may be useful to clinicians looking to obtain further visualization of lung pathologies and as a reliable means of detecting thoracic lesions indicative of interstitial pneumonia on-farm. These results can be used to aid the practitioner in determining appropriate further diagnostic testing and treatment strategies while awaiting confirmatory test results for diagnosis of MV.

Résultats de l'échographie et de la radiographie numérique chez des ovins atteints d'une maladie clinique associée à une infection à lentivirus des petits ruminants. La radiographie numérique et les images échographiques ont été utilisées dans cette série de cas pour évaluer quatre brebis d'un seul troupeau présentant une perte de poids chronique et un retard de croissance. À l'examen, tous les animaux présentaient une tachypnée, une dyspnée, une toux et étaient normothermiques avec des auscultations thoraciques anormales. Trois des quatre animaux ont été diagnostiqués avec une maladie respiratoire chronique associée à une infection Maedi-visna (MV) confirmée via des tests sérologiques. L'imagerie thoracique diagnostique a identifié des caractéristiques compatibles avec des lésions pathologiques associées à une pneumonie interstitielle chez les trois animaux atteints de MV; ces résultats étaient absents chez l'animal qui a été testé négatif pour MV.Message clinique clé :L'imagerie diagnostique peut être utile aux cliniciens qui cherchent à obtenir une visualisation plus poussée des pathologies pulmonaires et comme un moyen fiable de détecter les lésions thoraciques indiquant une pneumonie interstitielle à la ferme. Ces résultats peuvent être utilisés pour aider le praticien à déterminer d'autres tests de diagnostic appropriés et des stratégies de traitement en attendant les résultats des tests de confirmation pour le diagnostic de MV.(Traduit par Dr Serge Messier).

Miniature Companion Pig Sedation and Anesthesia.

With their increase in popularity in North America as pets, miniature companion pigs are in need of veterinary professionals familiar with sedation and anesthesia for the species. This article provides a review of the agents used for sedation, premedication, induction, and maintenance of anesthesia for miniature companion pigs. This review also covers species-specific anatomic and physiologic factors of miniature companion pigs with respect to administration of anesthetics, endotracheal intubation, anesthetic maintenance, and common complications so that the reader can make an informed anesthetic plan for the species.

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration.

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (V z ) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 µg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 µg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration.

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves.

Introduction: Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period. Methods: Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer. Results: Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3. Discussion: The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report.

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 µg/mL, 0.8 h, and 0.2 hr*µg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation.

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h-1) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.

Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcusequi subsp. zooepidemicus infection model in horses.

The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (Cmax ) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean Cmax /MIC was 1.30, and mean AUClast /MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.

Case Report: Successful Management of Refractory Keratomycosis in an Alpaca Using Penetrating Keratoplasty and Combination Antifungal Therapy (Caspofungin 0.5% and Terbinafine 1%).

Fungal keratitis is a common disease in certain parts of the world and affects several species, including equids, camelids, and homo sapiens, leading to blindness or loss of the eye if the infection is not adequately controlled. Reports of clinical use of antifungals caspofungin and terbinafine are limited across both veterinary and human medical literature. The alpaca presented in this case demonstrates that deep keratomycosis can be caused by Scopulariopsis brevicaulis and Fusarium verticillioides, two previously unreported fungi to cause keratomycosis in camelids. This report demonstrates successful management with a combination of surgery and topical ophthalmic treatment with caspofungin 0.5% solution and terbinafine 1% dermatologic cream, after initially failing treatment with topical voriconazole 1% solution. Combination therapy appears more effective than monotherapy with some fungal organisms, and synergy between antifungal agents is thought to play a role in the success of combination therapy. Surgery to remove the bulk of the fungal infection is especially helpful in cases that fail initial medical therapy.

Presentation, Clinical Pathology Abnormalities, and Identification of Gastrointestinal Parasites in Camels (Camelus bactrianus and Camelus dromedarius) Presenting to Two North American Veterinary Teaching Hospitals. A Retrospective Study: 1980-2020.

Old World Camelids (OWC) represent two species (Camelus bactrianus and Camelus dromedarius) with increasing numbers in North America. Gastrointestinal (GI) parasitism is a major cause of clinical disease in camelids and leads to significant economic impacts. Literature reporting on clinical parasitism of camels is localized to India, Africa, and the Middle East, with limited information available on OWCs in North America. Objectives of this study were to report on clinical presentation and diagnostic findings in Camelus bactrianus and Camelus dromedarius with GI parasitism and provide a comparative analysis between geographic regions. Medical records of OWCs presenting to two veterinary teaching hospitals (of the University of Tennessee and University of Wisconsin) were evaluated. Thirty-one camels including 11 Bactrians and six dromedaries (14 species not recorded) were included for the clinical component of this study, reporting on signalment, presenting complaint, and clinical pathology. Anorexia, weight loss, and diarrhea were the most common presenting complaint. Clinical pathology findings included eosinophilia, hypoproteinemia, and hyponatremia. For the second component of this study, a total of 77 fecal parasite examination results were evaluated for parasite identification and regional variation. Trichuris, Capillaria, Strongyloides, Nematodirus, Dictyocaulus, Moniezia, and protozoan parasites (Eimeria, Cryptosporidium, Giardia) were recorded. Strongyle-type eggs predominated, followed by Trichuris and Eimeria spp. There was a statistically significant variation in prevalence of coccidia between the two regions, with fecal examinations from Tennessee more likely to contain Eimeria (P = 0.0193). Clinicians treating camels in North America should recognize anorexia, weight loss, and diarrhea combined with clinical pathologic changes of hypoproteinemia, eosinophilia and hyponatremia as possible indications of GI parasitism. Clinicians should also consider the potential for regional variation to exist for GI parasites of camels in different areas of North America.