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- Author or Editor: Melissa T. Hines x
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Objective—To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses.
Animals—5 horses with adult-onset narcolepsy.
Procedure—Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values.
Results—Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean ± SD) for area under the curve was 3.9 ± 0.7 h × μg/ml, whereas volume of distribution was 584 ± 161.7 ml/kg, total body clearance was 522 ± 102 ml/kg/h, and mean residence time was 1.8 ± 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range.
Conclusions and Clinical Relevance—Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses. (Am J Vet Res 2001;62:783–786)
Objective—To compare the analgesic efficacy of administration of butorphanol tartrate, phenylbutazone, or both drugs in combination in colts undergoing routine castration.
Design—Randomized controlled clinical trial.
Animals—36 client-owned colts.
Procedures—Horses received treatment with butorphanol alone (0.05 mg/kg [0.023 mg/lb], IM, prior to surgery and then q 4 h for 24 hours), phenylbutazone alone (4.4 mg/kg [2.0 mg/lb], IV, prior to surgery and then 2.2 mg/kg [1.0 mg/lb], PO, q 12 h for 3 days), or butorphanol and phenylbutazone at the aforementioned dosages (12 horses/group). For single-drug–treated horses, appropriate placebos were administered to balance treatment protocols among groups. All horses were anesthetized, and lidocaine hydrochloride was injected into each testis. Physical and physiological variables, plasma cortisol concentration, body weight, and water consumption were assessed before and at intervals after surgery, and induction of and recovery from anesthesia were subjectively characterized. Observers assessed signs of pain by use of a visual analogue scale and a numerical rating scale.
Results—Significant changes in gastrointestinal sounds, fecal output, and plasma cortisol concentrations were evident in each treatment group over time, compared with preoperative values. At any time point, assessed variables and signs of pain did not differ significantly among groups, although the duration of recumbency after surgery was longest for the butorphanol-phenylbutazone–treated horses.
Conclusions and Clinical Relevance—With intratesticular injections of lidocaine, administration of butorphanol to anesthetized young horses undergoing routine castration had the same apparent analgesic effect as phenylbutazone treatment. Combined butorphanolphenylbutazone treatment was not apparently superior to either drug used alone.
OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days.
ANIMALS Twelve 2- to 14-day old healthy Arabian and Arabian-pony cross neonatal foals.
PROCEDURES A 1.27-cm strip of cream containing 7.3 mg of diclofenac sodium (n = 6 foals) or an equivalent amount of placebo cream (6 foals) was applied topically to a 5-cm square of shaved skin over the anterolateral aspect of the left tarsometatarsal region every 12 hours for 7 days. Physical examination, CBC, serum biochemistry, urinalysis, gastric endoscopy, and ultrasonographic examination of the kidneys and right dorsal colon were performed before and after cream application. Venous blood samples were collected at predefined intervals following application of the diclofenac cream, and plasma diclofenac concentrations were determined by liquid chromatography–mass spectrometry.
RESULTS No foal developed any adverse effects attributed to diclofenac application, and no significant differences in values of evaluated variables were identified between treatment groups. Plasma diclofenac concentrations peaked rapidly following application of the diclofenac cream, reaching a maximum of < 1 ng/mL within 2 hours, and declined rapidly after application ceased.
CONCLUSIONS AND CLINICAL RELEVANCE Topical application of the 1% diclofenac sodium cream to foals as described appeared safe, and low plasma concentrations of diclofenac suggested minimal systemic absorption. Practitioners may consider use of this medication to treat focal areas of pain and inflammation in neonatal foals.
Objectives—To establish maximum oxygen consumption (O2max) in ponies of different body weights, characterize the effects of training of short duration on O2max, and compare these effects to those of similarly trained Thoroughbreds.
Animals—5 small ponies, 4 mid-sized ponies, and 6 Thoroughbreds.
Procedure—All horses were trained for 4 weeks. Horses were trained every other day for 10 minutes on a 10% incline at a combination of speeds equated with 40, 60, 80, and 100% of O2max. At the beginning and end of the training program, each horse performed a standard incremental exercise test in which O2max was determined. Cardiac output (), stroke volume (SV), and arteriovenous oxygen content difference (C [a-v] O2) were measured in the 2 groups of ponies but not in the Thoroughbreds.
Results—Prior to training, mean O2max for each group was 82.6 ± 2.9, 97.4 ± 13.2, and 130.6 ± 10.4 ml/kg/min, respectively. Following training, mean O2max increased to 92.3 ± 6.0, 107.8 ± 12.8, and 142.9 ± 10.7 ml/kg/min. Improvement in O2max was significant in all 3 groups. For the 2 groups of ponies, this improvement was mediated by an increase in ; this variable was not measured in the Thoroughbreds. Body weight decreased significantly in the Thoroughbreds but not in the ponies.
Conclusions and Clinical Relevance—Ponies have a lower O2max than Thoroughbreds, and larger ponies have a greater O2max than smaller ponies. Although mass-specific O2max changed similarly in all groups, response to training may have differed between Thoroughbreds and ponies, because there were different effects on body weight. (Am J Vet Res 2000; 61:986–991)
Objectives—To assess safety and determine effects of IV administration of formaldehyde on hemostatic variables in healthy horses.
Animals—7 healthy adult horses.
Procedure—Clinical signs and results of CBC, serum biochemical analyses, and coagulation testing including template bleeding time (TBT) and activated clotting time (ACT) were compared in horses given a dose of 0.37% formaldehyde or lactated Ringer’s solution (LRS), IV, in a 2-way crossover design. In a subsequent experiment, horses received an infusion of 0.74% formaldehyde or LRS. In another experiment, horses were treated with aspirin to impair platelet responses prior to infusion of formaldehyde or LRS.
Results—Significant differences were not detected in any variable measured between horses when given formaldehyde or any other treatment. Infusion of higher doses of formaldehyde resulted in adverse effects including muscle fasciculations, tachycardia, tachypnea, serous ocular and nasal discharge, agitation, and restlessness.
Conclusions and Clinical Relevance—Intravenous infusion of formaldehyde at doses that do not induce adverse reactions did not have a detectable effect on measured hemostatic variables in healthy horses. (Am J Vet Res 2000;61:1191–1196)
Objective—To determine whether daily administration of pyrantel tartrate can prevent infection in horses experimentally challenged with Sarcocystis neurona.
Animals—24 mixed-breed specific-pathogen-free weanling horses, 10 adult horses, 1 opossum, and 6 mice.
Procedure—Sarcocystis neurona-naïve weanling horses were randomly allocated to 2 groups. Group A received pyrantel tartrate at the labeled dose, and group B received a nonmedicated pellet. Both groups were orally inoculated with 100 sporocysts/d for 28 days, 500 sporocysts/d for 28 days, and 1,000 sporocysts/ d for 56 days. Blood samples were collected weekly, and CSF was collected monthly. Ten seronegative adult horses were monitored as untreated, uninfected control animals. All serum and CSF samples were tested by use of western blot tests to detect antibodies against S neurona. At the end of the study, the number of seropositive and CSF-positive horses in groups A and B were compared by use of the Fisher exact test. Time to seroconversion on the basis of treatment groups and sex of horses was compared in 2 univariable Cox proportional hazards models.
Results—After 134 days of sporocyst inoculation, no significant differences were found between groups A and B for results of western blot tests of serum or CSF. There were no significant differences in number of days to seroconversion on the basis of treatment groups or sex of horses. The control horses remained seronegative.
Conclusions and Clinical Relevance—Daily administration of pyrantel tartrate at the current labeled dose does not prevent S neurona infection in horses. (Am J Vet Res 2005;66:846–852)