Plasma achiral and chiral pharmacokinetic behaviour of intravenous oxfendazole co-administered with piperonyl butoxide in sheep

Co-administration of piperonyl butoxide (PB) potentiates fenbendazole (FBZ) in small ruminants. The resultant increase in bioavailability of FBZ and its metabolite oxfendazole (OFZ) has important implications for the efficacy of these drugs against benzimidazole (BZD)-resistant strains of Teladorsagia circumcincta. This study evaluated the racemic (achiral) and enantiomeric (chiral) plasma disposition kinetics of OFZ and its metabolites after the co-administration of PB and OFZ in sheep. Six 6-8-month-old, parasite-free, female Dorset sheep (30-40 kg) were used in a two-phase crossover experiment. In phase I, three sheep received 30 mg/kg PB orally, followed by a single intravenous (i.v.) injection of OFZ at 5 mg/kg. The other three animals were treated similarly except that 5 mL of water replaced PB. In phase 2, treatments for the two groups were reversed and were given 14 days after the initiation of phase I. Three analytes OFZ, FBZ and fenbendazole sulphone (FBZSO(2)) were recovered in plasma up to 48 h post-treatment in both experimental groups. Achiral and chiral pharmacokinetic (PK) profiles for OFZ, after the co-administration of PB, were characterized by a significantly greater area under the concentration--time curve (AUC) and a longer mean residence time (MRT). Chiral OFZ distribution ratios were comparable in both treatment groups. Piperonyl butoxide treatment markedly influenced the plasma PK profiles for FBZ and FBZSO(2) following OFZ administration. Production of FBZ was enhanced as reflected by increased (> 60%) AUC, delayed T(max) and a significantly delayed (> 45%) elimination (t(1/2)(el)). Although AUC values for FBZSO(2) were not significantly different between groups, this metabolite was depleted more slowly from plasma (t(1/2)(el) > 60% and MRT > 42%) following PB treatment. This study demonstrated that PB co-administration is associated with an inhibition of OFZ biotransformation, as evidenced by the significantly higher plasma concentrations of OFZ and FBZ, and this could have important implications in terms of anti-parasite therapy against BZD-resistant parasite strains.     

Assessment of serum protein electrophoresis for monitoring therapy of naturally acquired equine cyathostomin infections

Serum protein electrophoresis (SPE) has previously been suggested as a means of assessing cyathostomin burdens in horses, although SPE used for that purpose is supported by little evidence. This clinical research report describes a study that objectively evaluated the use of SPE on a population of 38 horses following the administration of different anthelmintics. The population was subdivided into three groups, Groups F, M and P: 7.5 mg/kg bwt fenbendazole was administered to Group F on day -12; on day 0 0.4 mg/kg bwt moxidectin was administered to Group M and 19 mg/kg bwt pyrantel was administered to Group P. Faecal worm egg counts were obtained on days -14, 0 and 10. Groups M and P acted as controls for the Group F faecal egg count reduction test (FECRT) in which a high level of benzimidazole resistance was demonstrated. Group F was then used as a control group for the FECRT for both Groups P and M. A high anthelmintic efficacy of moxidectin and pyrantel was detected. SPE was performed on venous blood collected on days 0, 10, 30, 56 and 80. As the cyathostomins infecting the horses had been shown to be highly resistant to fenbendazole, Group F then served as a control group for comparison of any changes in protein fractions. Serum proteins did not vary significantly between groups on any of the sampling dates. No significant changes in serum proteins were observed in any group and no patterns were apparent on qualitative assessment of SPE profiles. SPE was therefore concluded to be an insensitive tool for the monitoring of cyathostomin treatment in horses in a clinical environment.     

Potentiation of the anthelmintic activity of oxfendazole by parbendazole

The ability of parbendazole (PBZ) to potentiate co-administered oxfendazole (OFZ) was investigated. Administration of a range (1.35-36.0 mg/kg) of doses of PBZ with 4.53 mg OFZ/kg demonstrated that significant potentiation occurred at 4.5 mg PBZ/kg. At 4.5 mg PBZ/kg, the area under the plasma OFZ concentration curve was about twice that obtained from oral administration of OFZ alone. When tested against benzimidazole-resistant Haemonchus contortus and Trichostrongylus colubriformis, the mixture of 4.5 mg PBZ + 4.53 mg OFZ/kg was significantly more effective than 4.53 mg OFZ/kg alone, and PBZ alone showed no activity against these resistant nematodes. The demonstration of PBZ-OFZ potentiation has indicated a means of obtaining a more effective use of currently available anthelmintics in the treatment of helminthiasis.     

Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs

The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.     

The evaluation of isoxsuprine hydrochloride for the treatment of navicular disease: a double blind study

A randomised double-blind clinical trial of 28 horses was undertaken to evaluate the efficacy of isoxsuprine hydrochloride at four different doses:- 0.0 mg/kg bodyweight (bwt) (placebo), 0.6 mg/kg bwt, 1.2 mg/kg bwt and 1.8 mg/kg bwt for treatment of navicular disease. The results showed that horses treated with isoxsuprine hydrochloride (N = 22) responded significantly with respect to clinical assessment score (P less than 0.01) when compared with the control group (N = 6). Furthermore, there were no dose-related differences in the responses of the horses treated with increasing levels of isoxsuprine. No correlation was found between radiological evidence of the extent of navicular disease and severity of lameness or response to treatment.     

Atropine reduces dobutamine-induced side effects in ponies undergoing a pharmacological stress protocol

REASONS FOR PERFORMING STUDY: High-dose dobutamine stress echocardiography has been shown to be cardiotoxic and arrhythmogenic in horses. However, the test may have benefit in practice as a pharmacological challenge of exercise without the treadmill being required. OBJECTIVES: To investigate the effect of low-dose dobutamine on cardiac performance in ponies previously treated with atropine, in order to develop a pharmacological protocol that allows examination of the equine heart under stimulation. METHODS: In 13 healthy Shetland ponies, heart rate (HR), stroke index (SI) and cardiac index (CI) were calculated from pulsed-wave Doppler ultrasound measurements performed at rest and during incremental steps of dobutamine infusion. Group 1 (n = 7) received dobutamine infusion at 2 microg/kg bwt/min for 5 mins followed by incremental rates of 5 microg/kg bwt/min every 5 mins, from 5 to 40 microg/kg bwt/min. Group 2 (n = 6) received dobutamine infusion in incremental rates of 1 microg/kg bwt/min, every 5 mins, from 2 microg/kg bwt/min to 5 microg/kg bwt/min, after premedication with 2 injections of 25 microg/kg bwt of atropine 5 mins apart. RESULTS: The increase in CI during the pharmacological challenge was higher in Group 2 and reached about 2.5 times the resting value. This increase in CI was mediated by a significant increase in HR in both groups, while SI significantly decreased in Group 1 and did not change significantly in Group 2. Ponies of Group 1, but not those of Group 2, showed excessive restlessness and cardiac arrhythmias during the pharmacological challenge and a high intragroup variability in cardiac response. CONCLUSIONS: The results of this study suggest that a low dose of dobutamine in ponies previously given atropine could be a helpful pharmacological protocol to perform stress echocardiography in equids. POTENTIAL RELEVANCE: Further studies should evaluate left ventricular wall motion in horses undergoing low-dose dobutamine protocol after pretreatment with atropine.     

Use of intravenous flecainide in horses with naturally-occurring atrial fibrillation

REASONS FOR PERFORMING STUDY: It has been reported that i.v. flecainide has a high efficacy for the treatment of experimentally-induced acute atrial fibrillation (AF) in horses and that its use is associated with minimal toxic side effects. OBJECTIVES: The objectives were to study the efficacy of i.v. flecainide as a treatment for atrial fibrillation in horses with naturally-occurring AF. METHODS: Ten horses with naturally-occurring AF were treated with 2 mg/kg bwt flecainide i.v. at a rate of 0.2 mg/kg bwt/min. In 3 horses, the infusion was continued at 0.05-0.10 mg/kg bwt/min until a total dose of 3.0 mg/kg bwt had been administered. Heart rate, QRS duration and average interval between fibrillation waves were measured before, during and following flecainide infusion. If conversion to normal sinus rhythm was not achieved, horses were treated with quinidine sulphate per os at a dose of 22 mg/kg bwt given every 2 h. RESULTS: None of the horses with chronic AF (n = 9) converted to sinus rhythm with flecainide i.v. The only horse treated successfully had acute AF of 12 days' duration. The QRS duration and fibrillation cycle length increased significantly (P = 0.006 and 0.002, respectively) during and following flecainide infusion. Heart rate did not increase significantly over time however, 3 horses developed heart rates in excess of 100 beats/min. Two horses developed a potentially dangerous ventricular dysrhythmia during the first 15 mins of treatment. Quinidine sulphate given per os restored sinus rhythm in 8 out of 9 horses, with minimal adverse effects. CONCLUSIONS: Although flecainide might be efficacious in cases of acute AF, it was not possible to restore sinus rhythm in horses with naturally-occurring chronic AF at the dosages used in this study. In 2 horses, 2.0 mg/kg bwt flecainide was associated with potentially dangerous dysrhythmias. POTENTIAL CLINICAL RELEVANCE: Intravenous administration of 2 mg/kg bwt flecainide is unlikely to convert chronic AF in horses and could induce dangerous dysrhythmias.     

Disposition of oxfendazole in goats and efficacy compared with sheep

The disposition of intraruminally administered oxfendazole (OFZ) in goats was studied at 5, 10 and 20 mg kg-1. The area under the plasma concentration with time curve (AUC) increased with increasing dose but at a declining rate. AUC was lower after intra-abomasal compared with intraruminal administration. OFZ was less effective against drug resistant Trichostrongylus colubriformis in goats than in sheep but was of similar efficacy against drug resistant Haemonchus contortus in both host species. In the same experiment peak plasma levels of OFZ in goats were about half those in sheep given the same dose. Of 70 goats tested in the field, total rumen bypass occurred in 12 per cent and partial bypass in 67 per cent. Lower systemic availability due to bypass would be expected to reduce further anthelmintic efficacy in goats. From the results of these experiments a dose rate of 10 mg kg-1 is recommended for goats. When given at this rate as a divided dose at 12 hourly intervals over 24 hours, OFZ was significantly more effective than a single dose in reducing egg counts.     

The effect of co-administration of parbendazole on the disposition of oxfendazole in sheep

The effect of intraruminal administration of parbendazole (PBZ) on the flow rate of bile and the pharmacokinetic behaviour of oxfendazole (OFZ) was examined in sheep. PBZ given at 18, 9 and 4.5 mg/kg resulted in a dose-related reduction in bile flow rate which was also inversely related to changing concentration of PBZ and its metabolites in plasma. Co-administration of 4.5 mg PBZ/kg with 5.0 mg [14C]-OFZ/kg resulted in increased concentrations of fenbendazole (FBZ), OFZ and fenbendazole sulphone (FBZ-SO2) in plasma, although total 14C levels remained unchanged compared with that observed when OFZ alone was administered. The presence of PBZ also reduced biliary secretion of 14C by 22% and altered the relative proportions of OFZ metabolites in bile during the 72-h experimental period. The ratio of 4'-hydroxy-OFZ (OH-OFZ) to 4'-hydroxy-FBZ (OH-FBZ) changed from 7:1 in the absence of PBZ to approximately 1:1 in the presence of PBZ. There was no change in urinary or faecal 14C excretion. The PBZ-induced effects were temporary since the pharmacokinetic behaviour of OFZ given alone two weeks before was similar to that given two weeks after PBZ co-administration. It is suggested that the presence of PBZ temporarily slowed hepatic metabolism and biliary secretion of OFZ metabolites but concomitantly increased extra-biliary transfer of OFZ and/or its metabolites from plasma into the gastrointestinal tract. Elevated exposure of parasites in the gut wall to plasma-derived drug, coupled with higher concentrations of anthelmintically active OH-FBZ secreted in bile, could contribute to the previously reported increased efficacy of OFZ when co-administered with PBZ.     

Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration

The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.     

Evaluation of dimethyl sulphoxide effects on initial response to endotoxin in the horse

REASONS FOR PERFORMING STUDY: Endotoxaemia is one of the most severe and ubiquitous disease processes in horses. Although dimethyl sulphoxide (DMSO) is used clinically in horses, there is no study indicating its efficacy in endotoxaemic horses. HYPOTHESIS: DMSO ameliorates the clinical response to i.v. lipopolysaccharide (LPS) administration. METHODS: Eighteen horses were assigned randomly to one of 4 groups: Normosol-LPS (0.2 mug/kg bwt, i.v.); DMSO (1 g/kg bwt, i.v.)-saline; high-dose DMSO (1 g/kg bwt, i.v.)LPS; low-dose DMSO (20 mg/kg bwt, i.v.)-LPS. Horses participating in the DMSO-saline group were later assigned randomly to one of the LPS groups. Data for physical parameters, white blood cell counts, plasma TNF-alpha, and blood lactate and glucose concentrations were examined for the effect of treatment using a repeated-measures mixed-model ANOVA. A value of P<0.05 was considered significant. RESULTS: Endotoxaemia occurred in all horses receiving LPS, as indicated by the clinical score, physical parameters, haemoconcentration and leucopenia. High-dose DMSO ameliorated the effect of LPS on fever. DMSO, at either dose, but did not have a significant effect on LPS-induced changes in all other evaluated parameters. CONCLUSIONS: In this study, DMSO had minimal effects on clinical signs of induced endotoxaemia in horses. The effects were manifested by amelioration of LPS-induced fever.     

Efficacy of oral and intravenous dexamethasone in horses with recurrent airway obstruction

REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. OBJECTIVES: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.     

Multicentre,controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses

Reasons for performing study: In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness. Objectives: To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared. Methods: Lame horses (n = 155) were used in a multicentre, controlled, randomised and double‐blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was given to 79 horses at a dose of 4.4 mg/kg bwt/12 h for 2 days, followed by 2.2 mg/kg bwt/12 h for 6 days. SBZ was given to 76 horses at 6.6 mg/kg bwt/12 h for 2 days, followed by 3.3 mg/kg bwt/12 h for 6 days. Efficacy of treatments was evaluated by clinicians in equine practices according to lameness progression throughout the study. Product ingestion was checked daily to evaluate product acceptability. Results: Although SBZ showed a statistically significant tendency to have a better efficacy than PBZ (Odds ratio = 2.7; P = 0.016), significance dissipated once the analysis was adjusted for some imbalanced baseline covariates, confirming that they were actually related to the apparent advantage of SBZ over PBZ. Product acceptability was significantly higher in the SBZ group than in the PBZ group (96.1% vs. 77.2%; P = 0.001). Conclusions: SBZ and PBZ did not show significant differences in alleviating lameness in horses. However, SBZ had better product acceptability when administered orally with some food. Potential relevance: SBZ is a good therapeutic alternative to PBZ in horses since there is no significant difference in alleviating lameness between the 2 therapies.     

Comparative efficacy, persistent effect, and treatment intervals of anthelmintic pastes in naturally infected horses.

Eighty horses were involved in a comparative, controlled, and randomised field study conducted in Australia and Brazil. This study was undertaken to address the duration of efficacy (by faecal egg count reduction) of four anthelmintic pastes and to measure the time required between treatments on horses naturally infected by gastrointestinal nematodes. The treatment interval was based on the egg reappearance period (ERP), defined as "the period after treatment when horses have reached a positive egg count equal or superior to 200 eggs per gram (epg) of faeces". Horses were ranked according to pre-treatment faecal egg counts and randomly allocated on Day 0 to one of the four treatment groups (n=16). Group A received a combination of ivermectin at 200 microg/kg and praziquantel at 1.5mg/kg, Group B received an ivermectin paste at 200 microg/kg, Group C received a reference product containing ivermectin at 200 microg/kg, Group D received a moxidectin paste at 400 microg/kg, and Group E received a placebo. Horses were individually faecal sampled at weekly interval from Days 0 to 70 after treatment and coprocultures were made on pooled samples at the pre-treatment time on D-7 in Brazil and D-6 in Australia.The nematode population was mainly composed of small strongyles (Cyathostominae, Gyalocephalus spp., Triodontophorus spp.). All products were efficient (>90% efficacy) until Day 42 with no statistical difference between groups. From Day 49 onwards, Group C reached the threshold, while Group B exceeded this threshold on Day 56. Groups A and D remained below 200 epg for the entire study period (70 days). The interval between two anthelmintic treatments can vary according to the threshold. The ERP was defined as the period after treatment while the output of eggs is negligible or considered as acceptable. The mean number of days calculated to recurrence of 200 epg and more was, respectively, 60 days for product A, 56 days for products B and C, and 64 days for product D. If treatments are combined with other methods of limiting exposure to infective larvae on pasture, the number of treatments required will be reduced even further.     

A review of the use of moxidectin in horses

Moxidectin has broad‐spectrum anti‐nematodal and anti‐arthropodal activities in the horse but is not effective against tapeworms or flukes. Moxidectin and ivermectin have the same efficacy against internal, adult parasites of horses. Moxidectin, however, is highly effective in eliminating encysted and hypobiotic larval stages of cyathostomins, whereas ivermectin is not. Treatment of horses with moxidectin results in an egg‐reappearance period (ERP) of 15–24 weeks. Because of its long ERP, moxidectin is labelled to be used at 12 week intervals. Moxidectin may provide protection against infection by ingested cyathostomin larvae for 2–3 weeks after it is administered. The larvicidal activity of moxidectin has often been compared to that of fenbendazole administered at either 7.5 or 10 mg/kg bwt for 5 consecutive days. The efficacy of fenbendazole, when administered daily for 5 consecutive days at 7.5 or 10 mg/kg bwt, against all stages of cyathostomins is often less than that of moxidectin because resistance of cyathostomins to benzimidazoles is prevalent worldwide, and the 5 day course of fenbendazole does not overcome this resistance. There are now reports of resistance of ascarids to moxidectin. Overt resistance of cyathostomins and a shortened egg re‐emergence period after treatment with moxidectin have been reported. Rapid removal of manure by natural fauna can significantly reduce larval nematode concentrations and thereby reduce intervals of anthelmintic treatment. Of the macrocyclic lactones, moxidectin has the least deleterious effect on faecal fauna.     

Efficacy of a single high oxfendazole dose against gastrointestinal nematodes in naturally infected pigs

The goal of the current experiment was to assess the clinical efficacy of oxfendazole (OFZ) administered as a single oral dose (30 mg/kg) to pigs naturally parasitized with Ascaris suum, Oesophagostomum spp., Metastrongylus spp. and Trichuris suis. Thirty-six local ecotype piglets were divided into three independent experiments, named I, II and III (n = 12 each), respectively. Each experiment involved two different groups (n = 6): Untreated Control and OFZ treated. Animals were naturally parasitized with A. suum (Experiments I, II and III), Oesophagostomum spp. (Experiments I and II), T. suis (Experiments II and III) and Metastrongylus spp. (Experiment I). Pigs in the treated group received OFZ (Synanthic^®, Merial Ltd., 9.06% suspension) orally at 30 mg/kg dose. At five (5) days post-treatment, animals were sacrificed and the clinical efficacy of the OFZ treatment was established following the currently available WAAVP guidelines for a controlled efficacy test. None of the animals involved in this experiment showed any adverse events during the study. OFZ treatment given as a single 30 mg/kg oral dose showed a 100% efficacy against all the nematode parasites present in the three experiments. In conclusion, under the current experimental conditions, OFZ orally administered to naturally parasitized piglets at a single dose of 30 mg/kg was safe and highly efficacious (100%) against adult stages of A. suum, Oesophagostomum spp., T. suis and Metastrongylus spp.     

Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Reasons for performing study: No studies have determined the pharmacokinetics of low‐dose amikacin in the mature horse. Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n = 6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n = 6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean ± s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144 ± 21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8 ± 7.44 µg/ml, area under the curve 139 ± 34.0 µg*h/ml, elimination half‐life 1.34 ± 0.408 h, total body clearance 1.25 ± 0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81 ± 0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (C_max) 19.7 ± 7.14 µg/ml and 21.4 ± 4.39 µg/ml and time to maximum concentration 65 ± 12.2 min and 115 ± 12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7 ± 5.34 µg/ml and after 24 h the mean concentration was 3.31 ± 1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean C_max : MIC ratio was 16.9 ± 1.80 in plasma, 4.95 ± 1.78 in synovial fluid, 5.36 ± 1.10 in peritoneal fluid and 3.18 ± 1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram‐negative bacteria. Potential relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.     

Use of guaiacol glycerine ether in clinical anaesthesia in the horse

A total of 103 anaesthetic inductions were performed in horses for a variety of elective procedures. All cases were premedicated with acepromazine maleate (0.02 to 0.05 mg/kg body weight [bwt] intramuscularly [im]). In 50 cases (Group A) anaesthesia was induced by a single intravenous (iv) bolus of thiopentone sodium (11.1 mg/kg bwt or 1 g/90 kg bwt) followed immediately by a bolus of suxamethonium chloride (0.1 mg/kg bwt). In 53 cases (Group B) anaesthesia was induced using iv guaiacol glycerine ether (GGE) (approximately 50 mg/kg bwt) followed by a bolus of thiopentone at half the usual dose rate (5.6 mg/kg bwt or 1 g/180 kg bwt). Induction of anaesthesia was uneventful in both groups although in Group B it was particularly smooth. Following endotracheal intubation anaesthesia was maintained with halothane in oxygen administered via a circle system. The duration of anaesthesia was comparable between the two groups; however, the mean (+/- sd) time to standing in Group B, 35 +/- 22 mins, was significantly shorter than in Group A, 48 +/- 25 mins. The use of the GGE/thiopentone technique is discussed.     

Pharmacokinetics of oxfendazole in red deer (Cervus elaphus)

The pharmacokinetics of oxfendazole (OFZ) in red deer (Cervus elaphus) was examined. OFZ, administered per os at 4.53 mg kg-1, was extracted in ether from plasma and identified and concentrations estimated by high pressure liquid chromatography. Irrespective of whether the animals were fed concentrates indoors as pellets or grass while on pasture, OFZ was absorbed rapidly. Concentrations of OFZ in plasma reached maxima within 20 hours (0.83 and 1.005 mg litre-1 respectively) and were undetectable 36 hours after administration. Fenbendazole was not detected at any time in the chromatograms. Metabolism of OFZ occurred rapidly producing the sulphone metabolite. In comparison with published data for OFZ in sheep, red deer appear to metabolise OFZ and excrete OFZ sulphone at much faster rates. Consequently, anthelmintic efficacy is likely to vary from species to species.     

Comparison of unfractioned and low molecular weight heparin for prophylaxis of coagulopathies in 52 horses with colic: a randomised double-blind clinical trial

REASONS FOR PERFORMING STUDY: Unfractioned heparin (UFH) is widely used for prophylaxis of coagulation disorders, especially in colic-affected horses. However, it is accompanied by certain side effects. OBJECTIVES: To compare the efficacy and side effects of unfractioned and low molecular weight heparin (LMWH) in horses with colic. METHODS: The study was carried out as a randomised, double-blind, controlled clinical trial. Fifty-two horses with colic were treated subcutaneously with either UFH (heparin calcium, 150 iu/kg bwt initially, followed by 125 iu/kg bwt q. 12 h for 3 days and then 100 iu/kg bwt q. 12 h) or LMWH (dalteparin, 50 iu/kg bwt q. 24 h). All horses underwent daily physical examination including assessment of jugular veins, local reaction to heparin injections, haematological evaluation and coagulation profiles over up to 9 days. RESULTS: The type of heparin used did not affect the general behaviour and condition. There were significantly more jugular vein changes in horses treated with UFH. Packed cell volume decreased significantly within the first few days of UFH treatment, but did not change significantly in horses treated with LMWH. Activated partial thromboplastin time (aPTT) and thrombin time (TT) were prolonged in horses treated with UFH but not in those treated with LMWH. CONCLUSIONS: It was concluded that, in comparison to UFH, LMWH has markedly fewer side effects in horses. POTENTIAL RELEVANCE: Therefore, LMWH is recommended for prophylaxis of coagulation disorders in colic patients.