OBJECTIVE To evaluate the pharmacokinetics of hydrocodone (delivered in combination with acetaminophen) and tramadol in dogs undergoing tibial plateau leveling osteotomy (TPLO). ANIMALS 50 client-owned dogs. PROCEDURES Dogs were randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate–acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard anesthetic and surgical protocols. Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication. RESULTS The terminal half-life, maximum serum concentration, and time to maximum serum concentration for tramadol following naïve pooled modeling were 1.56 hours, 155.6 ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum concentration determined by naïve pooled modeling was 7.90 ng/mL, and time to maximum serum concentration was 3.47 hours. The terminal half-life for hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption in some dogs and may not have been a robust estimate. Serum concentrations of hydromorphone were low. CONCLUSIONS AND CLINICAL RELEVANCE The pharmacokinetics of tramadol and metabolites were similar to those in previous studies. Serum tramadol concentrations varied widely, and concentrations of the active M1 metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor. Further study is warranted to assess variables that affect metabolism and efficacy of these drugs in dogs.

OBJECTIVE To investigate the safety of daily oral administration of grapiprant to dogs. ANIMALS Thirty-six 9-month-old Beagles of both sexes. PROCEDURES Dogs were randomly assigned to groups that received grapiprant via oral gavage at 0, 1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group, which included 4 additional dogs that were monitored for an additional 30 days after treatment concluded (recovery period). All dogs received ophthalmologic, ECG, and laboratory evaluations before treatment began (baseline) and periodically afterward. All dogs were observed daily. Dogs were euthanized at the end of the study for necropsy and histologic evaluation. RESULTS All dogs remained clinically normal during treatment, with no apparent changes in appetite or demeanor. Emesis and soft or mucoid feces that occasionally contained blood were observed in all groups, although these findings were more common in dogs that received grapiprant. In general, clinicopathologic findings remained within baseline ranges. Drug-related changes in serum total protein and albumin concentrations were detected, but differences were small and resolved during recovery. No drug-related gross or microscopic pathological changes were detected in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the 50 mg/kg group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.

OBJECTIVE To use CT-derived measurements to create a ferret-specific formula for body surface area (BSA) to improve chemotherapeutic dosing. ANIMALS 25 adult ferrets (19 live and 6 cadavers). PROCEDURES Live subjects were weighed, and body measurements were obtained by each of 3 observers while ferrets were awake and anesthetized. Computed tomography was performed, and a 3-D surface model was constructed with open-source imaging software, from which BSA was estimated. The CT-derived values were compared with BSA calculated on the basis of the traditional tape method for 6 cadavers. To further validate CT analysis software, 11 geometric shapes were scanned and their CT-derived values compared with those calculated directly via geometric formulas. Agreement between methods of surface area estimation was assessed with linear regression. Ferret-specific formulas for BSA were determined with nonlinear regression models. RESULTS Repeatability among the 3 observers was good for all measurements, but some measurements differed significantly between awake and anesthetized ferrets. Excellent agreement was found between measured versus CT-derived surface area of shapes, traditional tape– versus CT-derived BSA of ferret cadavers, and CT-derived BSA of cadavers with and without monitoring equipment. All surface area formulas performed relatively similarly. CONCLUSIONS AND CLINICAL RELEVANCE CT-derived BSA measurements of ferrets obtained via open-source imaging software were reliable. On the basis of study results, the recommended formula for BSA in ferrets would be 9.94 × (body weight)2/3; however, this represented a relatively minor difference from the feline-derived formula currently used by most practitioners and would result in little practical change in drug doses.