Effect of meloxicam and carprofen on renal function when administered to healthy dogs prior to anesthesia and painful stimulation

OBJECTIVE: To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine. ANIMALS: 6 male and 6 female healthy young-adult Beagles. PROCEDURE: A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia. RESULTS: Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.     

Effects of meloxicam on renal function in dogs with hypotension during anaesthesia

OBJECTIVE: To evaluate the effects of meloxicam on renal function in dogs anaesthetized and rendered hypotensive with acepromazine-thiopental-isoflurane. ANIMALS: Eight healthy beagles, four males and four females, 25.6 +/- 19.3 months old and weighing 12.8 +/- 2.0 kg. MATERIALS AND METHODS: Either meloxicam suspension at a dose of 0.133 mL kg(-1) (0.2 mg kg(-1)) or 0.133 mL kg(-1) saline solution (control), were given by mouth (PO) in a randomized, cross-over fashion. The treatment or control was given 3 hours before anaesthesia. Dogs were sedated with intramuscular acepromazine 0.1 mg kg(-1). Anaesthesia was induced with intravenous thiopental, followed by tracheal intubation and maintenance with isoflurane in oxygen and air, delivered using a semi-closed breathing system. Renal function was quantified using serum biochemistry, urinalysis and glomerular filtration rate measured by scintigraphy. Analysis of variance or Friedman anova were used for statistical analysis. RESULTS: Values (mean +/- SD) for mean arterial blood pressure did not differ significantly between treatments but was low (54 +/- 7 mmHg) during anaesthesia. Glomerular filtration rate did not differ significantly between treatments or over time, and results of urine and serum analysis were within reference ranges after meloxicam treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam caused no adverse effects on renal function when given to healthy dogs anaesthetized and rendered hypotensive with acepromazine, thiopental and isoflurane.     

Effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography in healthy beagle dogs

ObjectivesThe objective of this study was to evaluate the effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) in healthy dogs.AnimalsThirty-two healthy Beagles were used.MethodsMyocardial function was assessed in each dog by using 2D-STE, and the results were compared between young and old dogs.ResultsThe myocardial deformations in systole, besides the apical rotation rate, were not significantly different between young and old dogs. In contrast, the early diastolic circumferential strain rate, basal rotation rate, and torsion rate were significantly lower in old dogs than in young dogs (P = 0.03, P = 0.033, and P = 0.015, respectively). Late diastolic longitudinal and radial strain rates were significantly higher in old dogs than in young dogs (P = 0.002 and P = 0.018, respectively).ConclusionsYoung and old dogs showed similar systolic myocardial deformations, but significant differences in the values of some diastolic deformation variables were found between young and old dogs, highlighting the need for using age-matched control subjects in studies of diastolic function.     

The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs

Pimobendan is a benzimidazole‐pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three‐period, nested randomized two‐treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography–mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC_(0–∞) and C_max. Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half‐life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.     

Plasma lactate measurements in healthy beagle dogs

Plasma lactate concentrations were determined in venous blood samples collected from 60 healthy Beagles aged 5 to 9 months. The range of values (0.42 to 3.58 mmol/L) obtained with an enzymatic method in the present study was similar to values reported in smaller studies with the colorimetric procedures.     

Effect of tepoxalin on renal function in healthy dogs receiving an angiotensin-converting enzyme inhibitor

The objective of this study was to investigate renal function in clinically normal dogs receiving tepoxalin, a nonsteroidal inflammatory drug, either in association with or without an angiotensin-converting enzyme inhibitor (ACEI). Ten adult female Beagle dogs were used in the three phases of the study. The dogs were administered the drugs once daily for 7 days (experiment 1: placebo/tepoxalin/tepoxalin and benazepril; experiment 2: enalapril/tepoxalin and enalapril) or for 28 days (experiment 3: tepoxalin and benazepril together). Renal function was assessed by measurement of glomerular filtration rate (GFR) by renal scintigraphy [(renal uptake of 99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of 99mTc-DTPA. Compared with the placebo group, renal uptake and plasma clearance of 99mTc-DTPA were not significantly modified after a 7-day period of treatment with tepoxalin or enalapril alone, tepoxalin and benazepril or tepoxalin and enalapril together. No significant change was obtained in GFR after a 28-day period of dosing with tepoxalin and benazepril together. Therefore, it was concluded that tepoxalin did not alter renal function in healthy Beagle dogs receiving ACEI.     

Safety of a benazepril and pimobendan combination tablet in adult healthy dogs

The objective of the study was to investigate the safety of a combination tablet of benazepril and pimobendan, Fortekor PLUS^®, in a randomized, blinded, parallel‐group design study in healthy adult beagle dogs. The test article, Fortekor PLUS^® tablets, was administered orally twice daily for 6 months at one, two, and four times the highest recommended dosage of 0.5 mg/kg benazepril hydrochloride/0.25 mg/kg pimobendan (four males and four females per group). An additional control group was sham‐dosed. Fortekor PLUS^® did not induce any treatment‐related effects on body weight, food consumption, neurological, ophthalmologic or physical assessments over the 6‐month treatment period. The test article was possibly associated with an increased frequency of occasional vomiting. Fortekor PLUS^® was associated with small, but significant, increases in heart rate and reductions in PR and QT intervals, which were assessed by electrocardiography. These effects were most probably related to reflex tachycardia secondary to reduced systemic blood pressure. Statistically significant changes in some clinical pathology variables were noted after test article administration, but were considered to be of no clinical relevance as values remained within reference ranges and/or were not dose‐dependent. No treatment‐related macroscopic or microscopic findings were observed. In conclusion, Fortekor PLUS^® tablets were well tolerated in healthy adult dogs when administered at one, two, and four times the highest recommended dosage for 6 months.     

Influence of age on bronchoscopic findings in healthy beagle dogs

The aims of this study were to evaluate the effect of age on bronchoscopic features and bronchoalveolar lavage fluid (BALF) cellularity in dogs. Thirty healthy beagle dogs from three age groups were included: young dogs (10 months to 4.5 years of age; n = 8), middle-aged dogs (5–8 years old; n = 13) and older dogs (>8 years; n = 9). Haematology, thoracic radiography, bronchoscopy and bronchoalveolar lavage were performed; bronchoscopic findings were scored and BALF total and differential cell counts were determined. The total bronchoscopic score was higher in older dogs; these dogs had more irregular bronchial mucosa, more prominent mucosal vessels and bronchiectasis. Younger dogs had a higher percentage of neutrophils in BALF compared with middle-aged and old dogs and a higher percentage of lymphocytes in BALF compared with middle-aged dogs. The results show that age has an effect on bronchoscopic features of airways and the composition of BALF in the dog.     

Endoscopic evaluation of the gastroduodenal mucosa to determine the safety of short-term concurrent administration of meloxicam and dexamethasone in healthy dogs

OBJECTIVE: To evaluate the safety, with respect to the development of gastric ulcers and erosions, of concurrent administration of meloxicam and dexamethasone for 3 days to healthy dogs. ANIMALS: 20 conditioned purpose-bred research Beagles. PROCEDURE: Seven days prior to treatment, dogs were anesthetized for endoscopic evaluation of the upper portion of the gastrointestinal tract (ie, the gastric and duodenal mucosa). Five regions of the gastroduodenal area were scored by 2 investigators. Dogs were randomly assigned to 1 of 4 treatment groups as follows: saline-saline, dexamethasone-saline, saline-meloxicam, and dexamethasone-meloxicam groups. On days 1, 2, and 3, dogs received either dexamethasone or saline (0.9% NaCl) solution injections SC twice daily. On days 2, 3, and 4, dogs received either meloxicam or saline solution injections SC once daily. On day 2, dogs were anesthetized for a sham surgery (ie, electrostimulation). On day 5, the gastroduodenal area of each dog was reevaluated by use of endoscopic evaluation and histologic examination of biopsy specimens. RESULTS: The total endoscopic score of the dexamethasone-meloxicam group was significantly greater than the scores of the other groups. The dexamethasone-saline group had a mean cumulative score that was significantly greater than the saline-meloxicam or saline-saline groups. Endoscopic scores of the saline-meloxicam group were not significantly different from scores of the saline-saline group. No significant differences in histologic findings were found between groups. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, meloxicam appears to be safe with regard to adverse effects on the gastrointestinal tract. Concurrent administration of dexamethasone and meloxicam is more likely to cause gastric erosions than meloxicam administration alone.     

Effects of general anesthesia and surgery on renal function in healthy dogs

OBJECTIVES: To evaluate renal function in healthy dogs undergoing general anesthesia and ovariohysterectomy without concurrent IV administration of fluids. ANIMALS: 35 healthy client-owned dogs. PROCEDURE: Dogs were medicated with promazine hydrochloride (0.05 mg/kg of body weight, SC) approximately 45 minutes before induction of anesthesia with thiopental sodium (10 to 15 mg/kg, IV). Anesthesia was maintained with 2% halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students under the direct supervision of a veterinary surgeon. Renal function was assessed (serum urea and creatinine concentrations, fractional clearance of sodium, urine alkaline phosphatase [ALP] and gamma-glutamyltransferase [GGT] activities, urine specific gravity, and enumeration of renal tubular epithelial cells in urine sediment) prior to and 24 and 48 hours after surgery. RESULTS: Duration of general anesthesia ranged from 80 to 310 minutes. Urine specific gravity and ALP activity and serum urea and creatinine concentrations did not change over time. Fractional clearance of sodium decreased 24 and 48 hours after surgery, whereas urine GGT activity and the ratio of urine GGT activity to urine creatinine concentration increased 24 hours after surgery, compared with presurgery values. Renal tubular epithelial cells increased in number in urine sediment from 11 of 35 (31.4%) dogs and 5 of 35 (14.3%) dogs 24 and 48 hours after surgery, respectively. However, this increase was not clinically relevant. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fluids to healthy dogs undergoing general anesthesia and elective surgery may not be necessary for maintenance of renal homeostasis.     

Intradermal and serological testing for mites in healthy beagle dogs

Background – Intradermal testing (IDT) is widely used in veterinary medicine to select allergens for immunotherapy. The recommended concentration for mites is 250 protein nitrogen units (PNU)/mL. It is not known whether healthy dogs responding to this concentration have asymptomatic sensitization or irritation. Furthermore, interbatch and intersupplier variability of allergens has not been fully addressed. Hypothesis/Objectives – The incidence of positive IDTs in healthy beagles was recorded and the value of combining these results with serology to differentiate between asymptomatic sensitization and irritancy evaluated. Additionally, the interbatch and intersupplier variability of allergens was assessed. Animals – Seventeen healthy laboratory beagles with no history or clinical signs of canine atopic dermatitis were used. Methods – Intradermal tests were performed with four mite allergens from two suppliers (varying batches). An initial IDT at 250 PNU/mL was used to determine whether decreasing or increasing test concentrations were used in the subsequent titration IDTs. Additionally, two IgE ELISA tests from different manufacturers were performed. Results – Seven of 17 dogs showed IDT reactions at 250 PNU/mL. There were highly significant allergen interbatch and significant intersupplier correlations and agreement. The associations between the IDT reactions and the IgE serologies statistically identified two groups of dogs: one with positive serology and IDT reactions at 250 PNU/mL; and another with negative serology and IDT reactions. Conclusions and clinical importance – Our results suggest that dogs that have IDT reactions and positive serology are asymptomatically sensitized, while dogs that react at higher allergen concentrations, but have negative serology, do so as a result of irritant reactions.     

Effects of carprofen, meloxicam and deracoxib on platelet function in dogs

ObjectiveTo determine effects of anti-inflammatory doses of COX-2 selective NSAIDs carprofen, meloxicam, and deracoxib on platelet function in dogs and urine 11-dehydro-thromboxane B2.Study designRandomized, blocked, crossover design with a 14-day washout period.AnimalsHealthy intact female Walker Hounds aged 1–6 years and weighing 20.5–24.2 kg.MethodsDogs were given NSAIDs for 7 days at recommended doses: carprofen (2.2 mg kg^?1, PO, every 12 hours), carprofen (4.4 mg kg^?1, PO, every 24 hours), meloxicam (0.2 mg kg^?1, PO, on the 1st day then 0.1 mg kg^?1, PO, every 24 hours), and deracoxib (2 mg kg^?1, PO, every 24 hours). Collagen/epinephrine and collagen/ADP PFA-100 cartridges were used to evaluate platelet function before and during and every other day after administration of each drug. Urine 11-dehydro-thromboxane B₂ was also measured before and during administration of each drug.ResultsAll NSAIDs significantly prolonged PFA-100 closure times when measured with collagen/epinephrine cartridges, but not with collagen/ADP cartridges. The average duration from drug cessation until return of closure times (collagen/epinephrine cartridges) to baseline values was 11.6, 10.6, 11 and 10.6 days for carprofen (2.2 mg kg^?1 every 12 hours), carprofen (4.4 mg kg^?1 every 24 hours), meloxicam and deracoxib, respectively.Conclusions and clinical relevanceOral administration of some COX-2 selective NSAIDs causes detectable alterations in platelet function in dogs. As in humans, PFA-100 collagen/ADP cartridges do not reliably detect COX-mediated platelet dysfunction in dogs. Individual assessment of platelet function is advised when administering these drugs prior to surgery, particularly in the presence of other risk factors for bleeding.     

Pharmacokinetics of low‐dose methotrexate in healthy beagle dogs

Methotrexate may be an alternative to ciclosporin in the treatment of canine atopic dermatitis (cAD) as suggested by recent data. The aim of the study was to investigate both the tolerance and the pharmacokinetic behavior of methotrexate (MTX) in plasma, following intravenous (i.v.), subcutaneous (s.c.) or oral (OR) administration over several weeks. Six healthy dogs were given oral MTX once a week, respectively, per dog at 2.5 mg/1 week, 5 mg/4 weeks, 7.5 mg/3 weeks, 10 mg/6 weeks and 12.5 mg/5 weeks. No clinically relevant abnormalities of laboratory parameters were noticed. A high inter‐individual variation of MTX plasma concentration was observed with a suspicion of saturation phenomenon in absorption. To compare with other routes of administration, six healthy beagle dogs followed a crossover design study at 7.5 mg per dog MTX. The absolute bioavailability was 93% for SC injection and 30% for the oral route. The inter‐individual variability was quite low following SC administration compared to oral route. Just as in human, given the substantial variability of oral absorption, clinicians cannot assume consistent oral bioavailability of MTX. Therefore, they may consider switching dogs to the SC route in case of absence of clinical response with a weekly oral dose.     

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant‐bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 μg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady‐state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half‐life (T_1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T_1/2 was greater in renal failure patients than in normal patients. Sixty‐nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.     

Colonisation status of Malassezia pachydermatis on the hair and in the hair follicle of healthy beagle dogs

Hair and hair follicle carriage of Malassezia pachydermatis was studied in 12 healthy beagle dogs. The yeast was isolated from hair clipped from the lip region at 13 sites in nine dogs but was less frequently recovered from the interdigital spaces on the forefeet and from two sites on the trunk. Population sizes at the lip were significantly greater (P < 0.01) than those at other sites. Skin biopsy specimens were obtained from the same sites and epidermal and follicular tissues dissected following immersion in 1 M CaBr(2). Epidermal carriage of M. pachydermatis was identified in nine biopsy specimens taken from five dogs. Hair follicle carriage was identified in five skin specimens (four foot, one lip) from three dogs. This study indicates that M. pachydermatis is readily recovered from the distal hair in healthy dogs and that hair follicle carriage is infrequent or that populations are low at that site.     

Effect of fenoldopam on renal function after nephrotomy in normal dogs

OBJECTIVE: To evaluate effects of fenoldopam on renal function in normal dogs subjected to bisection nephrotomy. In addition, effects of bisection nephrotomy on renal function in normal dogs were evaluated. STUDY DESIGN: Controlled, randomized, blinded experiment. SAMPLE POPULATION: Sixteen mixed-breed adult dogs. METHODS: Dogs were paired for sex, body weight, and approximate age and assigned to 1 of 2 groups: fenoldopam (F) or placebo (P). Baseline glomerular filtration rate (GFR) based on quantitative renal scintigraphy using (99m)Tc-DTPA, blood urea nitrogen (BUN), serum creatinine (SCr), urinalysis, and urine culture were performed before surgery. Left nephrotomy was performed via median celiotomy. Group F dogs were administered intravenous (IV) fenoldopam (0.1 microg/kg/min) for 90 minutes, whereas group P dogs were administered an equivalent volume of saline (0.9 % NaCl) solution for 90 minutes. Temperature, heart rate, respiration, direct arterial blood pressure, and urine volume were recorded during anesthesia. Renal function was assessed by measuring SCr, BUN, and GFR at 1, 21, and 42 days after surgery. RESULTS: There was no significant difference between groups in measured physiologic variables. No significant difference in GFR, BUN, or SCr between groups or between operated or control kidneys was detected. CONCLUSIONS: Bisection nephrotomy in normal dogs with renal arterial occlusion of 15 minutes and using a simple continuous capsular closure does not adversely affect renal function. CLINICAL RELEVANCE: Bisection nephrotomy, as described in this study, does not decrease renal function; perioperative administration of renoprotective agents is not necessary in normal dogs.     

Effects of long-term oral administration of ketoprofen in clinically healthy beagle dogs

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.