Daytime profile of the intraocular pressure and tear production in normal dog

Objective  To evaluate the circadian rhythms of intraocular pressure (IOP) and tear production in dog exposed to a natural photoperiod.
Animals studied  We used 12 clinically healthy Beagles dog housed under natural photoperiod at indoor temperature and humidity.
Procedure  Intraocular pressure and Schirmer tear test (STT) I were measured every 4 h over a 48-h period in both eyes in each animal. Statistical analysis of the data was performed by one-way repeated-measures anova , Student's t -test, and single cosinor method.
Results  On each day, there was a highly significant effect of time on both parameters. A statistically significant difference of STT I values was observed comparing left and right eyes ( P  < 0.0001). Robust daily rhythms were observed for both parameters, IOP values showed diurnal acrophase (left eye: 09:33 ± 00:50 h; right eye: 09:25 ± 00:22 h), while STT I values showed nocturnal acrophase (left eye: 20:27 ± 00:46 h; right eye: 20:00 ± 00:05 h).
Conclusion  This study has demonstrated circadian rhythms in both IOP and STT I.     

Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog

The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.     

Pharmacokinetic evaluation of tramadol and its major metabolites after single oral sustained tablet administration in the dog: a pilot study

The study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N-O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100mg tablet to dogs. Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog while M2 and M5 were quantified in all of the dogs. The median values of C(max) (maximum plasma concentration), T(max) (time to maximum plasma concentration) and T(1/2) (half-life) for tramadol were 0.04 (0.17-0.02)mirog mL(-1), 3 (4-2) and 1.88 (2.211-1.435)h, respectively. M5 showed median values of C(max), T(max) and T(1/2) of 0.1 (0.19-0.09)microg mL(-1), 2 (3-1) and 4.230 (6.583-1.847)h, respectively. M2 showed median values of C(max), T(max) and T(1/2) of 0.22 (0.330-0.080)microg mL(-1), 4 (7-3) and 4.487 (6.395-1.563)h, respectively. The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog.     

Pharmacokinetic and urine profile of tramadol and its major metabolites following oral immediate release capsules administration in dogs

The aim of the present paper was to test the oral administration of oral immediate release capsules of tramadol in dogs, to asses both its pharmacokinetic properties and its urine profile. After capsules administration of tramadol (4 mg/kg), involving eight male Beagle dogs, the concentration of tramadol and its main metabolites, M1, M2 and M5, were determined in plasma and urine using an HPLC method. The plasma concentrations of tramadol and metabolites were fitted on the basis of mono- and non-compartmental models, respectively. Tramadol was detected in plasma from 5 min up to 10 h in lesser amounts than M5 and M2, detected at similar concentrations, while M1 was detected in negligible amounts. In the urine, M5 and M1 showed the highest and smallest amount, respectively; M1 and M5 resulted widely conjugate with glucuronic acid. In conclusion, after oral administration of tramadol immediate release capsules, the absorption of the active ingredient was rapid, but its rapid metabolism quickly transformed the parental drug to high levels of M5 and M2, showing an extensive elimination via the kidney. Hence, in the dog, the oral immediate release pharmaceutical formulation of tramadol would have different pharmacokinetic behaviour than in humans.     

Pharmacokinetics of intravenous tramadol in dogs

The purpose of this study was to determine the pharmacokinetics of tramadol and the active metabolite mono-O-desmethyltramadol (M1) in 6 healthy male mixed breed dogs following intravenous injection of tramadol at 3 different dose levels. Verification of the metabolism to the active metabolite M1, to which most of the analgesic activity of this agent is attributed to, was a primary goal. Quantification of the parent compound and the M1 metabolite was performed using gas chromatography. Pharmacodynamic evaluations were performed at the time of patient sampling and included assessment of sedation, and evaluation for depression of heart and respiratory rates. This study confirmed that while these dogs were able to produce the active M1 metabolite following intravenous administration of tramadol, the M1 concentrations were lower than previously reported in research beagles. Adverse effects were minimal, with mild dose-related sedation in all dogs and nausea in 1 dog. Analgesia was not documented with the method of assessment used in this study. Tramadol may be useful in canine patients, but additional studies in the canine population are required to more accurately determine the effective clinical use of the drug in dogs and quantification of M1 concentrations in a wider population of patients.     

Pharmacokinetics of tramadol and the metabolite O-desmethyltramadol in dogs

Tramadol is an analgesic and antitussive agent that is metabolized to O-desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half-life, volume of distribution, and total body clearance were 0.80 +/- 0.12 h, 3.79 +/- 0.93 L/kg, and 54.63 +/- 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 +/- 38% and half-life 1.71 +/- 0.12 h following tramadol 11 mg/kg p.o. M1 had a half-life of 1.69 +/- 0.45 and 2.18 +/- 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half-life, volume of distribution, and clearance of M1 were 0.94 +/- 0.09 h, 2.80 +/- 0.15 L/kg, and 34.93 +/- 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.     

Thromboelastographic profile for a dog with hypocoagulable and hyperfibrinolytic phase of disseminated intravascular coagulopathy

The objective of this study is to report the use of thromboelastography as a diagnostic tool for the hyperfibrinolytic phase of disseminated intravascular coagulopathy in a dog with metastatic haemangiosarcoma. We established a cytological (i.e. fine needle aspirate) and histopathological (i.e. excisional surgical biopsy) diagnosis of haemangiosarcoma in a 10-year-old male castrated Bichon Frise with multiple dark purple dermoepidermal nodules on the ventral abdomen and medial stifle areas, multiple small pulmonary nodules and a solitary liver mass. The dog was treated with chemotherapy (AC protocol). Forty-nine days after completion of four treatment cycles, the dog was presented for recheck. Complete blood count revealed anaemia and mild thrombocytopenia. Chemistry profile showed no significant abnormalities. Analysis of haemostasis consisted of prolonged clotting times (prothrombin time, activated partial thromboplastin time), mild hypofibrinogenaemia and increased D-dimers. A presumptive diagnosis of disseminated intravascular coagulopathy was made. A re-calcified thromboelastography was simultaneously done to confirm the coagulopathy. Thromboelastographic tracings correlated with the plasma-based test results showing hypocoagulability (prolonged clotting times and prolonged thromboelastography clot kinetics; weaker clot with decreased fibrinogen levels, platelet count and lower thromboelastography tracing amplitude) and hyperfibrinolysis (increased D-dimers and increased D-dimers and increased thromboelastography lysis parameters). Based on these results, the dog was considered to be in the hyperfibrinolytic phase of disseminated intravascular coagulopathy. Results of the conventional haemostasis tests supported those obtained on thromboelastography. Humane euthanasia was performed because of poor prognosis and progressive disease, making further follow-up unavailable. As demonstrated in this case report, thromboelastography was found to be a helpful diagnostic tool for the diagnosis and monitoring of the hyperfibrinolytic phases of disseminated intravascular coagulopathy.     

Determination of oral tramadol pharmacokinetics in horses

The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia. The purpose of this study was to determine the pharmacokinetics and elimination pattern in urine of tramadol and its metabolites after oral administration to horses. Tramadol was administered orally to six horses and its half-life, T_max and C_max in plasma were 10.1, 0.59 h, and 132.7 ng/mL, respectively. The half-life, T_max and C_max for M1 in plasma were 4.0, 0.59 h, and 28.0 ng/mL, respectively. Tramadol and its metabolites were detectable in urine between 1 and 24 h after the administration. In conclusion, the PK data reported in this study provides information for the design of future studies of tramadol in horses.     

Pharmacokinetics of intravenous and intramuscular tramadol in llamas

The purpose of this study was to determine the pharmacokinetics of tramadol and its metabolite M1 after intravenous and intramuscular administration to llamas. Tramadol, a centrally acting analgesic whose efficacy is a result of complex interactions between opiate, adrenergic and serotonin receptor systems, has been used clinically to treat moderate to severe pain in humans. The pharmacokinetic parameters of tramadol and M1 in plasma were examined following intravenous and intramuscular administration to six healthy male llamas. Tramadol half-life, volume of distribution at steady-state and clearance after intravenous administration were 2.12 ± 0.37 h, 4.02 ± 1.16 L/kg and 1728.73 ± 152.82 mL/h/kg, respectively. The bioavailability was 110 ± 21% and half-life 2.54 ± 0.31 h following intramuscular administration of tramadol. M1 had a half-life of 10.40 ± 2.90 h and 7.71 ± 0.54 h following intravenous and intramuscular administration of tramadol.     

Cystourethroscopy in the dog

Summary

The cystourethroscopic examination with cold light cystoscopes forms an essential part of a complete urological examination and is useful for diagnostic as well as surgical procedures. The fast and non‐invasive character of the procedure limits the inconvenience to the patient.

With the rigid non‐flexible scope its use is, however, limited to female dogs, unless in the male dog a urethro(s)tomy is performed.     

Haemobartonellosis in the dog

The literature on haemobartonellosis is reviewed. The condition in a dog is presented and the history, clinical signs and treatment are described.     

Neuroblastoma in the dog

A peripheral neuroblastoma is described in a two-year-old Japanese Akita with a vague illness and a palpable abdominal mass. Radiology confirmed the presence of a cranial abdominal mass which was determined to be inoperable at exploratory laparotomy. The tumour was believed to have originated in the adrenal glands. The problems of clinical and pathological diagnosis are discussed.     

Rabies in the dog

The presenting signs are described of 19 dogs that were observed from the time of presentation until death. Rabies was confirmed by laboratory tests in each case. Vicious behaviour was seen in only six dogs. Paralytic signs and/or abnormal behaviour--the so-called "dumb" rabies--were more frequent. Six of the dogs had received Flury strain LEP vaccination. Intense conjunctival congestion was an important diagnostic feature.     

Bacteriuria in the dog

The results of a retrospective study of 85 bacteriological cultures on urine samples from 64 dogs is presented. Fifty-three of the samples produced a pure growth of bacteria and Proteus spp was grown from 24 of those samples while Escherichia coli was grown from 13 samples and Staphylococcus spp from six samples. It was noted that a large majority of the Proteus spp isolates (87.5 per cent) were from females and conversely a large majority of the E. coli isolates 92.3 per cent came from males. A study of conditions concurrent with the urinary tract infection showed that many animals had underlying problems that could compromise the ability of their urinary tracts to withstand invasion by micro-organisms. The antibiotic sensitivity patterns of E. coli and Proteus spp are discussed and the value of various antimicrobial agents considered.