Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats.

The pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide after intravenous (i.v.) and oral (p.o.) administration were evaluated in adult cats. Three treatments were administered: a single i.v. dose of A77 1726 (4 mg/kg), a single oral dose of leflunomide (4 mg/kg), and multiple oral doses of leflunomide (2 mg/kg). Mean pharmacokinetic parameter values after a single i.v. dose of A77 1726 were distribution (A) and elimination (B) intercepts (15.2 µg/mL and 34.5 µg/mL, respectively), distribution and elimination half-lives (1.5 and 71.8 h, respectively), area under the curve (AUC(0 → ∞); 3723 µg*h/mL), mean residence time (MRT; 93 h), clearance (Cl(obs); 1.1 mL/kg/h), and volume of distribution at steady state (Vd(ss); 97 mL/kg). Mean pharmacokinetic parameter values after a single oral dose of leflunomide were absorption and elimination rate constants (0.3 1/h and 0.01 1/h, respectively), absorption and elimination half-lives (2.3 and 59.1 h, respectively), AUC(0 → ∞) (3966 µg*h/mL), and maximum observed plasma concentration (C(max); 38 µg/mL). The bioavailability after a single oral dose of leflunomide was 100%. The mean ± SD A77 1726 concentration that inhibited 50% lymphocytes (EC(50) ) was 16 ± 13.5 µg/mL. The mean ± SD maximum A77 1726 concentration (EC(max)) was 61.0 ± 23.9 µg/mL.

Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma.

BACKGROUND: Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. HYPOTHESIS: Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. ANIMALS: Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. METHODS: A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. RESULTS: Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P = .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P = .028), lack of intraoperative arrhythmias (P = .0075), and decreased surgical time (P = .0089). CONCLUSIONS AND CLINICAL IMPORTANCE: Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma.

The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA-Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA-Pt and 61% of dogs received two treatments of OPLA-Pt after amputation. Administration of two doses of OPLA-Pt did not have a significant effect on disease-free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease-free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.

Disposition of cyclosporine after intravenous and multi-dose oral administration in cats.

The aim of this study was to evaluate the disposition of cyclosporine after intravenous (i.v.) and oral administration and to evaluate single sampling times for therapeutic monitoring of cyclosporine drug concentrations in cats. Six adult male cats (clinically intact) were used. Two treatments consisting of a single i.v. cyclosporine (1 mg/kg) and multiple oral cyclosporine (3 mg/kg b.i.d p.o. for 2 weeks) doses. Whole blood cyclosporine concentrations were measured at fixed times by high performance liquid chromatography and pharmacokinetic values were calculated. Mean values for the i.v. data included AUC (7413 ng/mL.h), t1/2 distribution and elimination (0.705 and 9.7 h, respectively), Cmax (1513 ng/mL), and Vd(ss) (1.71 L/kg). Mean values for the oral data included AUC (6243 ng/mL.h), t1/2 of absorption and elimination (0.227 and 8.19 h, respectively), and Cmax (480.0 ng/mL). Bioavailability of orally administered cyclosporine was 29 and 25% on days 7 and 14 respectively. Whole blood comment cyclosporine concentration 2 h after administration (C2) better correlated with AUC on days 7 and 14 than trough plasma concentration (C12). The rate of oral cyclosporine absorption was less than expected and there was substantial individual variation. Therapeutic drug monitoring strategies for cyclosporine in cats should be re-evaluated.

Idiopathic pneumoperitoneum in a dog.

A 13-year-old, neutered male standard poodle with tachypnea and abdominal distension was diagnosed with pneumoperitoneum. Pneumoperitoneum can be due to a perforated gastrointestinal tract, penetrating abdominal wounds, gas-producing bacterial peritonitis, or it can be iatrogenically introduced during surgery. Idiopathic pneumoperitoneum is a condition diagnosed in humans after exclusion of perforated gastrointestinal tract and other known causes of free intra-abdominal gas. This report suggests that dogs may suffer from a similar syndrome.

Spontaneous regression of osteosarcoma in four dogs.

Spontaneous regression of primary malignant bone tumors is rare but has been reported in the human literature. To the authors' knowledge, spontaneous regression of primary bone tumors in dogs or cats has not been reported. Osteosarcoma (OSA) is the most common primary bone tumor in humans, and it has been reported that the incidence of OSA is 40 to 50 times greater in dogs than humans. In this report, high-grade OSA was diagnosed in biopsy specimens obtained from 4 dogs that subsequently underwent spontaneous regression without tumor-specific treatment. Osteosarcoma in dogs has characteristics similar to that of OSA in humans.

Effects of exercise intensity and duration on plasma beta-endorphin concentrations in horses.

OBJECTIVE: To determine the relationship between plasma beta-endorphin (EN) concentrations and exercise intensity and duration in horses. ANIMALS: 8 mares with a mean age of 6 years (range, 3 to 13 years) and mean body weight of 450 kg. PROCEDURE: Horses were exercised for 20 minutes at 60% of maximal oxygen consumption (VO2max) and to fatigue at 95% V02max. Plasma EN concentrations were determined before exercise, after a 10-minute warmup period, after 5, 10, 15, and 20 minutes at 60% VO2max or at the point of fatigue (95% VO2max), and at regular intervals after exercise. Glucose concentrations were determined at the same times EN concentrations were measured. Plasma lactate concentration was measured 5 minutes after exercise. RESULTS: Maximum EN values were recorded 0 to 45 minutes after horses completed each test. Significant time and intensity effects on EN concentrations were detected. Concentrations were significantly higher following exercise at 95% VO2max, compared with those after 20 minutes of exercise at 60% VO2max (605.2 +/- 140.6 vs 312.3 +/- 53.1 pg/ml). Plasma EN concentration was not related to lactate concentration and was significantly but weakly correlated with glucose concentration for exercise at both intensities (r = 0.21 and 0.30 for 60 and 95% VO2max, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: A critical exercise threshold exists for EN concentration in horses, which is 60% VO2max or less and is related to exercise intensity and duration. Even under conditions of controlled exercise there may be considerable differences in EN concentrations between horses. This makes the value of comparing horses on the basis of their EN concentration questionable.

Equine plasma beta-endorphin concentrations are affected by exercise intensity and time of day.

Eight mature mares were exercised for 20 min at 60% VO2max and to fatigue at 95% VO2max. Plasma beta-endorphin (EN) concentrations were determined before exercise, after a 10 min warm-up, and at the end of each exercise test. Mean +/- s.e. beta-endorphin concentrations were significantly (P < 0.05) higher following work at 95% VO2max when compared to that at 60% VO2max (420.0 +/- 102.7 vs. 269.9 +/- 30.69 pg/ml). Pre-exercise samples were collected between 1000 and 1500 h. In order to evaluate whether any cyclic changes in EN secretion effects may have influenced results, a subsequent study was completed using 12 horses to assess diurnal fluctuations in EN concentrations, by measuring EN concentration every 2 h for a 24 h period. There was no statistical difference in mean values at any time between 0800 and 2000 h. Whether individual differences in EN concentrations reflected varying degrees of stress associated with the exercise could not be determined. Any possible link between EN concentration and exercise stress in exercising horses awaits clarification.

Laparoscopic diagnosis of subcapsular splenic hematoma in a horse.

A 5-year-old Quarter Horse was examined after it developed signs of abdominal discomfort as a result of a training accident. Oral mucous membranes were pale, and capillary refill time was > 3 seconds. Hematologically, the PCV was low, and abdominocentesis yielded a serosanguineous fluid. Abdominal ultrasonography was performed and revealed a large hypoechoic mass associated with the cranial margin of the spleen. Because differentiation between subcapsular hematoma and extracapsular hematoma could not be made with certainty, further evaluation of the spleen was indicated. Abdominal laparoscopy was performed, with the horse standing, to evaluate the extent, severity, and nature of the splenic hematoma. Laparoscopic examination revealed a 7.5-cm-diameter splenic hematoma contained within the splenic capsule, confirming the diagnosis of subcapsular splenic hematoma. Abdominal laparoscopy provided excellent observation of the spleen and allowed for thorough evaluation and determination of the extent of the lesion. This information aided the clinician in reaching a definitive diagnosis and choosing between splenectomy and medical treatment.