Little brainiacs and big dummies: Are we selecting for stupid, stout, or small dogs?

Background: Brain size has been associated with intelligence of various orders and families of animals, leading to the concept of encephalization. Brain size scales with body weight between species within mammals to approximately the 0.67 power. However, within species, this scaling exponent appears to be much smaller (approximately 0.27 power). Aim: We examined whether this relationship has persisted in dogs over the 120 years since this was originally observed. Methods: Comparative cross-sectional study of magnetic resonance imaging (MRI) data obtained from 127 dogs, compared to historical data from 157 dogs and 24 non-dog canid species. Results: Brain size in dogs measured by MRI had a scaling exponent virtually identical to that observed previously (0.24 vs. 0.26). However, the proportionality constant was smaller, suggesting that dogs in the study cohort had relatively smaller brains than the historical cohort. Absolute brain size appeared to have both a lower and upper limit in dogs. When compared to non-dogs canids, the most appropriate "representative" size for a "typical dog" when examining allometric scaling across Canidae appeared to be approximately 10-15 kg. Conclusions: We interpreted the slight reduction in relative brain size to be a function of increased obesity in the study cohort compared to dogs examined 120 years ago. Further, we suggest that dog brains have a finite lower size limit. Finally, concepts of encephalization should not be applied to dogs.

In vivo detection of microstructural spinal cord lesions in dogs with degenerative myelopathy using diffusion tensor imaging.

BACKGROUND: Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. OBJECTIVE: Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. ANIMALS: Thirteen dogs with DM and 13 aged-matched controls. METHODS: All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. RESULTS: Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition.

Interthalamic adhesion size in aging dogs with presumptive spontaneous brain microhemorrhages: a comparative retrospective MRI study of dogs with and without evidence of canine cognitive dysfunction.

OBJECTIVE: Spontaneous brain microhemorrhages in elderly people are present to some degree in Alzheimer's disease patients but have been linked to brain atrophy in the absence of obvious cognitive decline. Brain microhemorrhages have recently been described in older dogs, but it is unclear whether these are associated with brain atrophy. Diminution of interthalamic adhesion size-as measured on MRI or CT-has been shown to be a reliable indicator of brain atrophy in dogs with canine cognitive dysfunction (CCD) in comparison with successfully aging dogs. We hypothesized that aging dogs with brain microhemorrhages presenting for neurologic dysfunction but without obvious features of cognitive decline would have small interthalamic adhesion measurements, like dogs with CCD, compared with control dogs. The objective of this study was to compare interthalamic adhesion size between three groups of aging (>9 years) dogs: (1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of cognitive dysfunction (2) dogs with CCD (3) dogs without clinical evidence of encephalopathy on neurologic examination (control dogs). MR images from 52 aging dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. RESULTS: All interthalamic adhesion measurement parameters were significantly (P < 0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/15; 80%) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/25; 12%). Affected dogs without cognitive dysfunction had significantly more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct disease category.

Efficacy of frameless stereotactic radiotherapy for the treatment of presumptive canine intracranial gliomas: A retrospective analysis (2014-2017).

The use of conventional multi-fractionated radiotherapy for the treatment of glial tumours is well documented in the literature. Recently, stereotactic radiotherapy (SRT) has become more widely available allowing for hypo-fractionated protocols; however, its usefulness in the treatment of canine intracranial gliomas is largely undetermined. We conducted a retrospective analysis, including 21 dogs diagnosed with presumptive intracranial gliomas treated with one or more courses of three fractions of 8 to 10 Gy CyberKnife SRT. The objective of this study was to evaluate the efficacy, safety and prognostic factors associated with the use of SRT for the treatment of canine intracranial gliomas. Overall MST for all dogs was 636 days (d). Dogs treated with one course of the described SRT protocol had a MST of 258 days while those treated with >1 course had a MST of 865 days (P = .0077 log rank, 0.0139 Wilcoxon). Dogs treated with one course of SRT who received adjuvant chemotherapy had a MST of >658 days and lived significantly longer than those who did not receive chemotherapy (MST, 230 days) (P = .0414 log rank, 0.0453 Wilcoxon). The most common adverse event included presumptive transient demyelination in 3/21 dogs, which was treated successfully with corticosteroids in all patients. This study provides evidence that SRT is effective in prolonging survival in dogs with intracranial gliomas, and may provide similar results to conventional fractionated protocols, while decreasing the number of hospital visits and anaesthetic episodes. Additionally, it appears that patients can be safely treated with multiple rounds of SRT resulting in improved survival times.

Pharmacokinetics of Single-Dose Oral Pregabalin Administration in Normal Cats.

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing. Animals: Six healthy adult research cats. Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software. Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 µg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 µg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 µg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals. Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1-2 mg/kg q 12 h), should be evaluated in prospective clinical studies.

Histopathologic characteristics of biopsies from dogs undergoing surgery with concurrent gross splenic and hepatic masses: 125 cases (2012-2016).

OBJECTIVE: To investigate the histopathologic characteristics of concurrent splenic and liver masses in dogs undergoing splenectomy and liver mass biopsy/resection. Medical records of 125 client-owned dogs found to have splenic mass or masses and a liver mass or masses during surgery were examined. Signalment (age, sex, breed), body weight, and results of histopathology were recorded for all dogs. RESULTS: Twenty-seven percent (34/125) of the dogs in this study had no evidence of malignancy in either the liver or the spleen. Sixty of 125 dogs (48.0%) had malignancy in the spleen and liver, and 56 (56/60, 93.3%) of those dogs had the same malignancy in both organs. Signalment was similar to that in other reports of splenic pathology. In this clinical population of dogs, 27% of dogs with concurrent gross splenic and liver masses discovered intraoperatively had benign lesions in both locations and therefore had a favorable prognosis.

A Subset of Dogs with Presumptive Idiopathic Epilepsy Show Hippocampal Asymmetry: A Volumetric Comparison with Non-Epileptic Dogs Using MRI.

MRI-acquired volumetric measurements from 100 dogs with presumptive idiopathic epilepsy (IE) and 41 non-epileptic (non-IE) dogs were used to determine if hippocampal asymmetry exists in the IE as compared to the non-IE dogs. MRI databases from three institutions were searched for dogs that underwent MRI of the brain and were determined to have IE and those that were considered non-IE dogs. Volumes of the right and left hippocampi were measured using Mimics® software. Median hippocampal volumes of IE and non-IE dogs were 0.47 and 0.53 cm3, respectively. There was no significant difference in overall hippocampal volume between IE and non-IE dogs; however, IE dogs had greater hippocampal asymmetry than non-IE dogs (P < 0.012). A threshold value of 1.16 from the hippocampal ratio had an 85% specificity for identifying IE-associated asymmetry. Thirty five percent of IE dogs had a hippocampal ratio >1.16. Asymmetry was not associated with any particular hemisphere (P = 0.67). Our study indicates that hippocampal asymmetry occurs in a subset of dogs with presumptive idiopathic/genetic epilepsy, suggesting a structural etiology to some cases of IE.

Transnasal, Endoscopically Guided Skull-Based Surgery by Pharyngotomy for Mass Removal from the Sphenopalatine Sinus in a Horse.

OBJECTIVE: To report a transnasal, endoscopically guided ventral surgical approach for accessing the cranial and caudal segments of the sphenopalatine sinus for mass removal in a horse. STUDY DESIGN: Case report. ANIMAL: Adult horse with acute onset blindness referable to a soft tissue mass within the sphenopalatine sinus. CLINICAL REPORT: A 7-year-old Warmblood gelding presented with a history of running into a fence and falling. No neurologic signs were identified at initial examination but acute blindness was noted 3 weeks later. On computed tomography (CT) the sphenopalatine sinus was filled with a large homogeneous mass with poor contrast enhancement that extended dorsally with thinning to the dorsal cortex of the sphenoid bone, just rostral to the entrance of the optic canals into the cranial cavity. Surgical access to the sphenopalatine sinus was achieved using a transnasal, endoscopically guided ventral pharyngotomy approach and the mass lesion was removed. A presumptive diagnosis of chondroma was made based on histopathology. The horse recovered well from surgery, and although it has not regained vision as of 6.5 years postoperatively, the disease has not progressed. CONCLUSION: Transnasal, endoscopically-guided ventral surgical access to the sphenopalatine sinus is possible in horses and may improve access in horses with disease extending caudally beyond the palatine portion of the sinus. Use of smaller diameter or specialized instruments, such as various endoscopic bone cutting instruments, and CT image guidance may improve sinus access by this route.

Kyphosis and Kyphoscoliosis Associated with Congenital Malformations of the Thoracic Vertebral Bodies in Dogs.

Congenital malformations of the thoracic vertebral bodies are commonly encountered in veterinary practice. These anomalies are prevalent in juvenile and adult small-breed dogs. These anomalous vertebrae typically result in various degrees of kyphosis and scoliosis in the region of the abnormality. They are thought to occur following developmental errors during embryonic or fetal vertebral segmentation and ossification; most are incidental. This article focuses on those anomalies of the thoracic vertebral bodies that lead to clinical signs of neurologic dysfunction. Based on a limited number of reported cases, the prognosis for surgically managed dogs with thoracic vertebral body abnormalities is favorable.

Characteristics and Survival of 121 Cats Undergoing Excision of Intracranial Meningiomas (1994-2011).

OBJECTIVE: To report clinical features and outcomes of cats undergoing excision of intracranial meningiomas. STUDY DESIGN: Retrospective, multicenter case series. SAMPLE POPULATION: One hundred and twenty-one cats. METHODS: Signalment, clinical signs, duration of clinical signs, preoperative drug therapy, diagnostic imaging reports, surgery, histopathology, and outcome were collected from records of cats undergoing excision of intracranial meningiomas. Survival estimates were made using Kaplan-Meier analysis. RESULTS: There were 76/121 neutered males and 83/121 domestic short-hairs. Body weight ranged from 1.5-8.7 kg (median 5.0 kg). Age at diagnosis ranged from 3-18 years (median 12 years). Clinical signs included changes in behavior, ataxia, seizures, visual deficits, circling, and paresis. Duration of neurologic signs ranged from <1-23 months (median 1.25 months). At the time of writing, 13 cats were alive, 54 were dead or euthanatized, and 54 were lost to followup. Seven cats (13% of cats that died; 6% of all cats) died or were euthanatized in the immediate postoperative period (<1 month post-surgery) and 9 cats (17% of all cats that died; 7% of all cats) died from causes related to the meningioma but outside the immediate perioperative period. The median survival time for all cats was 37 months (95% confidence interval 28-54 months). CONCLUSION: Cats undergoing excision of intracranial meningiomas had a low perioperative mortality and a long-term prognosis of more than 3 years.

Medical infrared thermal imaging of cats with hyperthyroidism.

OBJECTIVE: To determine the usefulness of medical infrared thermal imaging (MITI) as a screening tool for hyperthyroidism in cats, evaluate the need for hair clipping over the ventral aspect of the neck to achieve optimal images, and determine whether there is a change in thermal patterns at 1 and 3 months after radioactive sodium iodide I 131 treatment. ANIMALS: 17 cats with and 12 control cats without hyperthyroidism. PROCEDURES: All cats underwent MITI first with the hair present and then after the hair was clipped. Each cat with hyperthyroidism was subsequently appropriately treated SC with radioiodide; reevaluations, including MITI before and after hair clipping and measurement of serum thyroxine concentration, were performed 1 and 3 months after treatment. RESULTS: The MITI had 80.5% and 87.5% accuracy in differentiating hyperthyroid cats from clinically normal cats before and after the hair over the ventral aspect of the neck was clipped. Among cats with an initial serum thyroxine concentration > 4.0 µg/dL, the success rate for MITI-detected response to radioiodide treatment at the 1-month reevaluation was 92.86% in unshaved cats and 85.71% in shaved cats. The success rate for MITI-detected response to radioiodide treatment at the 3-month reevaluation was 100% in unshaved and shaved cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that MITI was successful in differentiating between hyperthyroid cats and clinically normal cats and identifying patients with thyroxine concentration within reference interval after radioactive sodium iodide I 131 treatment.

Severe hyperthermia, hypernatremia, and early postoperative death after transethmoidal cavitron ultrasonic surgical aspirator (CUSA)-assisted diencephalic mass removal in 4 dogs and 2 cats.

OBJECTIVE: To report clinical findings including severe hyperthermia and hypernatremia after transethmoidal Cavitron ultrasonic surgical aspirator (CUSA)-assisted diencephalic mass removal. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 4) and 2 cats. METHODS: Medical records (1997-2003) of dogs and cats that had transethmoidal CUSA-assisted diencephalic mass removal were reviewed. Retrieved data were: history, signalment, blood work, neurologic examination findings, MRI results, histopathology, postoperative complications, pre- and postoperative medical therapy, and outcome. RESULTS: Tumor types included: meningioma (n = 3), choroid plexus papilloma (1), astrocytoma (1), and pituitary macroadenoma (1). Median onset of hyperthermia was 3.5 hours (range: 1-6 hours) after extubation; median high temperature at onset was 40.3°C, (range: 39.6-41.7°C). Median onset of hypernatremia (median, 172 mmol/L; range: 168-196 mmol/L) was 4.5 hours (range: 1-9 hours) after extubation. Median time of death after hyperthermia was 10.5 hours (range: 6-13 hours) and after extubation was 13.5 hours (range: 11-15 hours). CONCLUSIONS: Transethmoidal CUSA-assisted diencephalic mass removal is associated with early postoperative hyperthermia, hypernatremia, and death, and cannot be recommended.

Morphometric features of the craniocervical junction region in dogs with suspected Chiari-like malformation determined by combined use of magnetic resonance imaging and computed tomography.

OBJECTIVE: To objectively describe morphometric features of the craniocervical junction region of Cavalier King Charles Spaniels (CKCSs) and non-CKCS dogs with suspected Chiari-like malformation (CLM) and identify associations between these features and the presence of other malformations in this region. ANIMALS: 216 CKCSs and 58 non-CKCS dogs. PROCEDURES: Magnetic resonance and computed tomographic images of the head and craniocervical junction region of patients evaluated because of suspected CLM were assessed for cerebellar compression (CC), ventral spinal cord compression at the C1-C2 articulation (medullary kinking), and dorsal spinal cord compression at the C1-C2 articulation (dorsal compression). A compression index was calculated for each of these 3 locations in each dog. Multiple logistic regression analysis was performed to determine whether breed (CKCS vs non-CKCS) and compression index values were associated with the presence of other craniocervical junction abnormalities. RESULTS: All 274 dogs had CC; medullary kinking was identified in 187 (68.2%) and dorsal compression was identified in 104 (38.0%). Atlantooccipital overlapping (AOO) was identified in 76 (27.7%) dogs. Breed of dog (CKCS vs non-CKCS) and value of CC index were the only significant predictors of AOO. The CKCSs had an almost 5-fold decrease in risk of AOO, compared with the non-CKCS dogs, and the risk of AOO nearly doubled for every 10% increase in CC index. CONCLUSIONS AND CLINICAL RELEVANCE: The anatomic abnormality responsible for CC was AOO in a substantial percentage of dogs suspected to have CLM. The CC index value may be used to help differentiate subtypes of craniocervical junction abnormalities in dogs.

Spinal cord nephroblastoma in dogs: 11 cases (1985-2007).

OBJECTIVE: To evaluate clinical features and outcome of dogs with a confirmed spinal cord nephroblastoma and to describe the use of Wilms tumor-1 (WT-1) immunohistochemical staining to confirm a diagnosis of nephroblastoma in dogs. DESIGN: Retrospective case series. Animals-11 dogs with a spinal cord nephroblastoma. PROCEDURES: Medical records of dogs with a spinal cord nephroblastoma were reviewed. Information extracted included signalment, history, clinical signs, results of diagnostic testing, tumor location, treatment, and outcome. The diagnosis was confirmed through histologic review and WT-1 immunohistochemical staining of a tumor sample. In dogs with negative results for staining with WT-1, staining for cytokeratin, vimentin, and glial fibrillar acidic protein was performed. RESULTS: 11 dogs had a spinal cord tumor with a histologic appearance and immunohistochemical staining consistent with a nephroblastoma. Positive results for staining with WT-1 were detected in 9 of 11 dogs. Age at admission ranged from 5 to 48 months (median, 14 months). Nine dogs were female. All had progressive paraparesis, paraplegia, or ataxia. Duration of clinical signs ranged from 2 to 60 days (median, 14 days). Median survival time was 30 days from the time of diagnosis. Median survival time in dogs treated via surgical resection was 70.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis for dogs with a spinal cord nephroblastoma appeared to be poor, although combined surgical resection and radiation therapy may provide a good functional outcome. Results for staining with WT-1 can be used to support a diagnosis of nephroblastoma.

Surgical treatment of a meningoencephalocele in a cat.

OBJECTIVE: To report the clinical signs, imaging findings and surgical treatment of a meningoencephalocele in a cat. STUDY DESIGN: Case report. ANIMAL: Domestic shorthaired cat, 4 months old. METHODS: A parietal meningoencephalocele was identified and characterized by magnetic resonance and computed tomography (CT) imaging. The abnormal tissue was excised and submitted for histopathology, and the meningeal and skull defects were reconstructed. RESULTS: The cat made a full recovery and the episodes of aggression, restlessness and apparent discomfort that occurred before surgery ceased after surgical treatment. The cat was clinically normal 1 year postoperatively. CONCLUSION: Surgical management of meningoencephalocele in cats may be a viable treatment option.

Mycophenolate mofetil treatment in dogs with serologically diagnosed acquired myasthenia gravis: 27 cases (1999-2008).

OBJECTIVE-To compare clinical outcome in dogs with serologically diagnosed acquired myasthenia gravis (MG) treated with pyridostigmine bromide (PYR) with that of dogs treated with mycophenolate mofetil (MMF) and PYR (MMF + PYR). DESIGN-Retrospective case series. ANIMALS-27 dogs. PROCEDURES-Medical records from August 1999 through February 2008 were reviewed to identify dogs with serologically diagnosed acquired MG treated with PYR or MMF + PYR. Data collected for each dog included signalment, whether the dog had megaesophagus or pneumonia (or both), thyroid hormone concentration, remission, time to remission, and survival time. Rates for detection of clinical signs and survival time were compared. Survival time was estimated via the Kaplan-Meier method. Influence of drug treatment protocol on likelihood of remission, time to remission, and survival time was examined. Effects of MMF treatment, megaesophagus, pneumonia, and low serum thyroid hormone concentration on time to remission and survival time were also analyzed. RESULTS-12 dogs were treated with PYR, and 15 were treated with MMF + PYR. Mortality rates were 33% (PYR) and 40% (MMF + PYR). There was pharmacological remission in 5 and 6 dogs in the PYR and MMF + PYR groups, respectively. No significant differences were detected between treatment groups for remission rate, time to remission, or survival time. Megaesophagus, pneumonia, and low serum thyroid hormone concentration had no significant effect on time to remission or survival time for either treatment group. CONCLUSIONS AND CLINICAL RELEVANCE-The results did not support routine use of MMF for the treatment of dogs with acquired MG.

Congenital diseases of the craniocervical junction in the dog.

Craniocervical junction disorders are most frequently seen in toy and small-breed dogs. They can present a diagnostic challenge, as multiple anomalies can be present concurrently and share similar clinical manifestations. Some, such as Chiari-like malformations, may be present in asymptomatic dogs. A thorough evaluation of the entire craniocervical junction, frequently using more than 1 imaging modality, is necessary before making treatment decisions.

Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy.

OBJECTIVE: To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. DESIGN: Open-label, noncomparative clinical trial. ANIMALS: 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. PROCEDURES: Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. RESULTS: Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Pharmacokinetics of single-dose oral pregabalin administration in normal dogs.

OBJECTIVE: To describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose. STUDY DESIGN: Prospective experiment. ANIMALS: Six adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6-5.6) years old (median and range) weighing 33.4 (26.8-42.1) kg. METHODS: After jugular vein catheterization, the dogs received a single oral dose of pregabalin ( approximately 4 mg kg(-1)). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables. RESULTS: No adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5-92.1) microg hour mL(-1); absorption half-life = 0.38 (0.25-1.11) hours; elimination half-life = 6.90 (6.21-7.40) hours; time over 2.8 microg mL(-1) (the presumed minimal effective concentration) = 11.11 (6.97-14.47) hours; maximal plasma concentration (C(max)) = 7.15 (4.6-7.9) microg mL(-1); time for C(max) to occur = 1.5 (1.0-4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8-8.1), 8.8 (7.3-10.9), and 13.0 (8.8-15.2) microg mL(-1). The corresponding values assuming a 12-hour interval were 3.8 (2.4-4.8), 6.8 (4.9-7.9), and 10.1 (6.6-11.6) microg mL(-1). CONCLUSIONS AND CLINICAL RELEVANCE: Pregabalin 4 mg kg(-1) PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.