Use of Recombinant Canine Granulocyte Colony-Stimulating Factor to Decrease Myelosuppression Associated with the Administration of Mitoxantrone in the Dog

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.     

Hematologic Toxicosis Associated with Doxorubicin Administration in Cats

The hematologic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Complete blood and platelet counts were performed daily during the first treatment cycle. They were monitored before treatment for all remaining cycles, and at the average neutrophil nadir (day 8) starting with cycle 4. Significant poikilocytosis developed after the first treatment and remained throughout the study, although anemia did not occur. No other red blood cell abnormalities were seen. Platelet counts remained within the reference range throughout the first treatment cycle, but mild thrombocytopenia (88,000-288,000/uL) was found in 11.3% of subsequent complete blood counts (CBCs). Thrombocytosis was seen in 30.9% of CBCs. Neutropenia did not occur during the first treatment cycle although neutrophil counts did decrease, with the nadir occurring between days 8 and 11. All neutrophil counts returned to pretreatment values by day 14. Neutropenia was documented after 14 of 46 (30.4%) doxorubicin treatments, and was associated with fever in 5 cats (10.9%). All fevers responded to oral antibiotic therapy. Neutropenia that lasted more than 14 days developed in two cats, necessitating dosage reduction to 25 mg/m2 BSA. At the dose used in this study, doxorubicin administration was associated with acceptable hematologic toxicosis in most cats.     

Evaluation of Recombinant Canine Granulocyte Colony-Stimulating Factor as an Inducer of Granulopoiesis: A Pilot Study

Five healthy young adult dogs were given recombinant canine granulocyte colony-stimulating factor (rcG-CSF) at a dosage of 5 micrograms/kg/day subcutaneously for 4 weeks to evaluate the effect on complete blood cell counts. The mean neutrophil counts +/- standard deviation (SD) increased significantly (P less than 0.01) from 6,537/microliters +/- 1,726 (range, 4,950-9,512/microliters) to 26,330/microliters +/- 7,066 (range, 15,368-35,785/microliters) within 24 hours after the first injection of rcG-CSF. Mean monocyte counts +/- SD were significantly increased (P less than 0.05) from baseline values of 751/microliters +/- 168 (range, 444-891/microliters) to 2,514/microliters +/- 878 (range, 1,740-3,752/microliters) on day 5 of rcG-CSF administration. Mean neutrophil and monocyte counts (+/- SD) continued to increase reaching a maximum of 72,125/microliters +/- 15,073 (range, 50,915-96,278/microliters) and 3,972/microliters +/- 2,621 (range, 685-8,030/microliters), respectively by day 19. These increased neutrophil and monocyte counts were maintained until the administration of rcG-CSF was stopped. Blood counts returned to normal within 5 days after discontinuing the rcG-CSF. One week after discontinuing treatment, rcG-CSF was started again at 5 micrograms/kg/day subcutaneously. Within 48 hours following administration of rcG-CSF, mean neutrophil counts +/- SD increased from 5,860/microliters +/- 1,819 (range, 3,720-8,650/microliters) to 57,444/microliters +/- 8,173 (range, 43,983-68,278/microliters). Myeloid:erythroid ratios increased from a mean of 1.63:1 on day 1 prior to administration of rcG-CSF to 3.3:1 on day 10 in three dogs for which bone marrow samples were evaluated. Recombinant canine G-CSF did not cause clinically significant toxicosis in any of the dogs.     

Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma

Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.     

Evaluation of efficacy of selamectin, fipronil, and imidacloprid against Ctenocephalides felis in dogs

OBJECTIVE: To evaluate efficacy of monthly administration of selamectin, fipronil, and imidacloprid against Ctenocephalides felis in dogs. DESIGN: Randomized controlled trial. ANIMALS: 44 healthy dogs. PROCEDURE: Dogs known to be free of fleas were infested with 100 unfed adult fleas on days -28 and -21. On days 0, 30, 60, 90, and 120, dogs (12/group) were treated by topical administration of selamectin (6 mg/kg [2.7 mg/lb] of body weight), fipronil (7.5 mg/kg [3.4 mg/lb]), or imidacloprid (10 mg/kg [4.5 mg/lb]); 8 untreated dogs were used as controls. On day -6 and every 2 weeks after initial treatment, comb counts of viable adult fleas were made, and fleas (< or =50/dog) were replaced onto the dog from which they were removed. On day 89, fleas were not replaced. On day 91 and every 7 days until the end of the study, dogs were challenged with 20 adult fleas. RESULTS: 14 days after initial treatment, geometric mean flea counts were reduced by 97.5 to 99.1 % for all treatments, compared with pretreatment counts on day -6. Selamectin, fipronil, and imidacloprid reduced geometric mean flea counts by 99.7 to 100% from day 29 to the end of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Selamectin is as effective as fipronil and imidacloprid in reducing C felis infestation in dogs housed for 3 months in a flea-infested environment under conditions known to support the flea life cycle, and in protecting against subsequent weekly challenges with C felis for an additional 2 months.     

Neutropenia associated with vincristine and L-asparaginase induction chemotherapy for canine lymphoma

Vincristine (VCR) and L-asparaginase (L-ASP) are commonly used to treat canine lymphoma. As single agents, these drugs are not myelosuppressive. However, in combination, VCR and L-ASP cause severe neutropenia in some dogs. It has been recommended that L-ASP be administered 12-24 hours after VCR to minimize toxicity. The purpose of this retrospective study was to determine the prevalence of neutropenia after VCR/L-ASP induction therapy for canine lymphoma and to evaluate risk factors for myelosuppression, especially the interval between VCR and L-ASP administration. Medical records of 147 dogs were reviewed. L-ASP was given 0 (n = 50), 6 (n = 23), 18 (n = 20), or 24 (n = 54) hours after VCR. Forty percent of the dogs were neutropenic 7 days after VCR/L-ASP, and 18% had neutrophil counts of <1,000 cells/microL. The median neutrophil count was 3,712 cells/microL (range 0-30,968 cells/microL). No correlation was found between administration interval and day 7 neutrophil count (P = .84) or development of gastrointestinal signs, including vomiting (P = .80), diarrhea (P = .52), and decreased appetite (P = .30). No significant predictors of neutropenia were identified. Higher clinical stage and substage b were associated with decreased appetite after treatment (P = .04 and .01, respectively). Sixteen percent of the dogs were hospitalized. This study demonstrates that VCR/L-ASP induction for canine lymphoma may result in neutropenia but that separation of VCR and L-ASP administration may not be necessary to avoid toxicity.     

Effect of Recombinant Canine Granulocyte Colony-stimulating Factor on Peripheral Blood Neutrophil Counts in Normal Cats

Recombinant canine granulocyte colony-stimulating factor (rcC-CSF) was administered subcutaneously at a dosage of 5 μg/kg/day to five healthy, young adult cats for 42 days. Mean neutrophil counts ± standard deviation increased significantly ( P > 0.001) from 10,966/μL ± 2324 to 30,688/μL ± 5296 within 24 hours after administration of the first dosage of rcG-CSF. Mean neutrophil counts reached 52,978/μL ±11,207 on day 6, representing a second significant increase ( P > 0.01) over the previous 5 days. Mean neutrophil counts continued to increase, reaching 66,994/μL ± 12,419 on day 14, then remaining within a range of 66,994 to 87,839/μL throughout the remainder of the study. The maximum mean neutrophil count was 87,839/μL ± 8,695 on day 42. Neutrophil counts remained high until the administration of recombinant canine granulocyte colony-stimulating factor was discontinued 42 days after initiation of therapy. Once the rcG-CSF administration was discontinued, neutrophil counts returned to pretreatment values within 5 days. There were no significant changes in numbers of any of the other cell lines. There was no clinically significant toxicosis associated with the administration of rcGCSF.     

Clinical efficacy of selamectin in the treatment of naturally acquired infection of sucking lice (Linognathus setosus) in dogs

A clinical study was performed in 21 dogs to evaluate the efficacy of selamectin for the treatment of naturally acquired infection of sucking lice (Linognathus setosus [L.setosus]) in dogs. Each dog was randomly assigned to one of two treatment groups. One group was treated with selamectin applied topically at a mean dosage of 7.9 mg/kg. The other group was treated with permethrin applied topically at a mean dosage of 85.7 mg/kg. At day 42 posttreatment, all animals remaining in the study (10 treated with selamectin and six with permethrin) were clear of lice. In both groups, the reduction in lice counts from pretreatment values to day 42 was statistically significant at P< or =0.0001. Selamectin applied topically appeared to be effective against L. setosus infection in dogs.     

Weekly administration of low-dose doxorubicin for treatment of malignant lymphoma in dogs

Nine dogs with intermediate- or high-grade lymphoma were prospectively entered into a protocol to be given a total of 15 weekly doses of doxorubicin (10 mg/m2 of body surface, IV) in an attempt to eliminate all clinical evidence of neoplasia, with minimal risk of drug toxicity. Eight of these dogs did not complete the protocol because of progression of the disease. The median number of doses administered to dogs that developed progressive disease before the regimen was completed was 5 (range, 2 to 9). Seven dogs achieved partial (n = 5) or complete (n = 2) remission, with median duration of 14 days (range, 7 to 231 days). The dog that was given all 15 weekly treatments remained in complete remission for 231 days. Complete remission that lasted for 14 days was observed in another dog. Toxicosis developed in 3 dogs; signs of toxicosis were generally mild and included colitis (n = 1), vomiting (n = 1), neutropenia (n = 1), and lethargy (n = 1). The lowest neutrophil count (1,876 cells/microliter) was seen in one dog after 7 doses of doxorubicin were given. Doxorubicin at dosage of 10 mg/m2/wk appears to be safe, but is generally ineffective for treatment of lymphoma.     

Diagnostic importance of vitamin K1 and its epoxide measured in serum of dogs exposed to an anticoagulant rodenticide

Administration of vitamin K1, SC, to anticoagulant-poisoned (diphenadione) dogs provided diagnostic information within 4 hours, when vitamin K1 and its epoxide were measured in canine sera. Twelve dogs (2 groups of 6) were given 2.5 mg of diphenadione/kg of body weight for 3 days. Dogs were treated with vitamin K1, 2.5 (n = 6) or 5 mg/kg/day (n = 6) SC for 21 days, and their responses were compared. Four nonexposed control dogs were given 5 mg of vitamin K1/kg/day. Serum concentration of vitamin K epoxide was significantly (P less than 0.02) higher in diphenadione-exposed dogs than in control dogs 1 to 4 hours after the initial vitamin K1 treatment on day 4. Vitamin K epoxide/vitamin K1 ratios were similarly higher and became more distinct. Cessation of vitamin K1 therapy on day 24 resulted in prolongation of one-stage prothrombin times in diphenadione-exposed dogs, becoming clearly evident on day 27. Serum vitamin K1 concentrations were not detectable on day 27 in diphenadione-exposed dogs, whereas serum vitamin K1 concentrations were readily detectable in control dogs. One-stage prothrombin time changes, during days 24 to 32, indicated 5 mg of vitamin K1/kg provided better protection than did 2.5 mg of vitamin K1/kg. Coagulopathy in the dogs was resolved by day 32.     

Dose titration and confirmation tests for determination of cesticidal efficacy of epsiprantel in dogs

Fifty-five dogs, naturally infected with Taenia sp or Dipylidium caninum or both, were assigned to the following treatment groups for dose titration studies with epsiprantel: nonmedicated control dogs (n = 14), medicated dogs given a dosage of 2.75 mg/kg of body weight (n = 15), medicated dogs given a dosage of 5.5 mg/kg (n = 16), and medicated dogs given a dosage of 8.25 mg/kg (n = 10). Medication was given orally in a tablet formulation. Feces were examined for cestodes passed and the gastrointestinal tract was examined at necropsy for retained cestodes. Efficacy of epsiprantel was 92.9% against Taenia and 44.8% against Dipylidium for a dosage of 2.75 mg/kg, 100% against Taenia and 99.8% against Dipylidium for a dosage of 5.5 mg/kg, and 94.6% against Taenia and 100% against Dipylidium for a dosage of 8.25 mg/kg. For dose confirmation, 36 dogs naturally infected with Taenia sp or D caninum or both were allotted to 2 treatment groups: nonmedicated control dogs (n = 16) and dogs medicated with epsiprantel at a dosage of 5.5 mg/kg (n = 20). Efficacy was 100% for both Taenia sp and D caninum.     

Evaluation of ifosfamide for treatment of various canine neoplasms

lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.     

Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital

The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1, 5, 7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.     

A comparison of toxicity of two dosing schemes for doxorubicin in the cat

Doxorubicin is a commonly used and effective treatment for a variety of tumors in both people and cats. However, the use of this drug in cats has been associated with side effects such as renal injury, myelosuppression, anorexia, and weight loss. The goal of this study was to compare the toxicities associated with two dosing schemes for doxorubicin in tumor-bearing cats. Group A cats received 1mg/kg of doxorubicin, while group B cats received 25mg/m2 of doxorubicin plus 22ml lactated Ringer's solution per kilogram body weight subcutaneously. Toxicities were evaluated using laboratory data, physical examination, and history, and were graded using a standardized scale and compared between groups. Post-treatment neutrophil counts were significantly lower among cats in group B compared to cats in group A (P< or =0.001), although complete blood counts were not evaluated at identical intervals in all cases. No other significant differences in the type, frequency or severity of clinical or laboratory toxicities were noted between groups, and no episodes of sepsis were recognized in either group. The results of this study suggest that higher doses of doxorubicin may not be associated with an increased risk of toxicity in the cat. Additional studies are still indicated to determine optimal dosing for doxorubicin in this species.     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Effects of short courses of different doses of prednisone and dexamethasone on serum third component of complement (C3) levels in dogs.

The effect of different doses of prednisone and dexamethasone on serum C3 levels was determined in 35 dogs. Dogs in Group A (n = 15) were administered prednisone (1.1 mg/kg/day) for 14 days; dogs in Group B (n = 10) were given prednisone at 2.2 mg/kg/day for 7 days; dogs in group C (n = 10) were administered dexamethasone (0.25 g/kg/day) for 7 days. Serum C3 concentrations were determined using a sandwich ELISA in samples obtained before and after glucocorticoid administration. Concentrations were expressed as a percentage of a reference standard. No statistically significant differences were found after glucocorticoid administration in all groups. Thus, short-term administration of prednisone and dexamethasone at commonly used doses did not result in significantly lower serum C3 levels.     

A comparison of two pamidronate dosing protocols on bone turnover in normal dogs and dogs with osteosarcoma

Introduction: Dogs with appendicular osteosarcoma (OSA) excrete higher concentrations of urine cross‐linked N‐telopeptide of type I collagen (NTx) than normal dogs. NTx is a specific biochemical marker of osteoclastic activity. Pamidronate is a bone‐modulating agent that exerts potent inhibitory effects on osteoclasts. The use of pamidronate is currently being evaluated for the management of osteolytic bone pain in dogs with appendicular osteosarcoma. Despite pamidronate's increasing usage in veterinary oncology, optimal dosing has yet to be determined. Commonly utilized dosages range from 1–2 mg/kg, given intravenously (IV) as a 2‐hour constant rate infusion every 28 days. The purpose of this prospective study was to compare the biological activity of two pamidronate doses (1 mg/kg vs. 2 mg/kg) in the suppression of urine NTx excretion in normal dogs and dogs with appendicular osteosarcoma. Methods: Seventeen OSA dogs receiving single‐agent pamidronate as palliative therapy were evaluated. Group 1A (n = 10) received a dose of 1 mg/kg and group 2A (n = 7) received a dose of 2 mg/kg IV. Urine NTx level were measured at day 0 and 28 using a commercial ELISA (Ostex International). Urine NTx level were also measured in 6 normal dogs: Group 1B (n = 3) received a dose of 1 mg/kg and group 2B (n = 3) received a dose of 2 mg/kg. In normal dogs, urine NTx levels were recorded weekly for six consecutive weeks. Results: In dogs with osteosarcoma, greater reductions in urine NTx excretion from baseline values were demonstrated at 2 mg/kg versus 1 mg/kg (57% and 23%, respectively). Likewise, in normal dogs, urine NTx excretion was suppressed to a greater extent with a dosage of 2 mg/kg versus 1 mg/kg (69% and 23%, respectively). Conclusion: Pamidronate possesses biologic activity in both normal dogs and in dogs with osteosarcoma, as assessed by reductions in urine NTx excretion. Based upon reductions in urine NTx excretion, a dosage of 2 mg/kg appears more effective than 1 mg/kg.     

Pharmacokinetics of a controlled‐release liposome‐encapsulated hydromorphone administered to healthy dogs

The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (C_MAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

Serum concentration and safety of intravenous drip versus subcutaneous administration of carboplatin in dogs

Carboplatin is used to treat certain cancers in dogs and cats and is routinely administered via intravenous drip (IVD). Subcutaneous (SC) administration has also been described. However, the toxicity, serum concentrations, and area under blood concentration-time curves (AUCs) of SC carboplatin are unknown. This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events. In this crossover study, five dogs received SC or IV carboplatin (300 mg/m²). After a minimum of 3 weeks, each dog received the other treatment. No gross skin toxicity or abnormal clinical signs were observed in any of the dogs. Blood test abnormalities were detected in most dogs. Decreased neutrophil and platelet counts, and increased C-reactive protein (CRP) levels were found. There was no significant difference in the neutropenia, thrombocytopenia, and CRP scores between the groups. Systemic toxicities of SC carboplatin were comparable to those of IVD carboplatin. The time to maximum carboplatin concentration after SC was longer than that after IVD (P<0.001). SC carboplatin remained in the serum longer than IVD carboplatin (P=0.008). The AUC of SC was less than that of IVD (P=0.002). The AUC and time taken to reach the maximum concentration of SC carboplatin were lower than those of IVD carboplatin. This study suggests that SC carboplatin may be an efficacious option for the treatment of tumors in dogs, particularly where IVD administration is challenging.