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1.
The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

2.
A study was undertaken to determine the toxic effects of cisplatin, an antineoplastic agent, when administered immediately after a 1-hour saline diuresis. Four treatments with cisplatin (70 mg/m2 of body surface, q 3 wk) were administered IV to 6 healthy dogs over a 20-minute period after 0.9% NaCl (saline) solution was administered IV for 1 hour at a volume of 132 ml (kg)0.75. Each dog vomited at least once within 8 hours after each treatment was administered. Clinical status, body weight, and food consumption were normal throughout the 12-week study for 5 of the 6 dogs. The sixth dog developed acute renal failure and became acutely blind and deaf within 3 days after the fourth treatment with cisplatin. Serum electrolyte, creatinine, and urea nitrogen values remained within established normal limits in all dogs immediately prior to each treatment, and in 5 of 6 dogs evaluated 3 weeks after the final treatment. The serum creatinine value (3.3 mg/dl) obtained from the Beagle euthanatized 2 weeks after the fourth treatment was above established normal values. Despite normalcy for all but 1 of the creatinine values, serum creatinine concentration obtained 3 weeks after the final treatment with cisplatin was significantly (P = 0.0001) higher than pretreatment values. When compared with data from all other evaluation periods, significant decreases in glomerular filtration rate, as determined by exogenous (P less than or equal to 0.0001) and endogenous (P less than or equal to 0.0001) creatinine clearance testing, were identified 3 weeks after the fourth treatment with cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

3.
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.  相似文献   

4.
OBJECTIVE: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. DESIGN: Prospective nonrandomized clinical trial. ANIMALS: 25 dogs. PROCEDURE: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h).The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. RESULTS: 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.  相似文献   

5.
This study prospectively describes the systemic toxicity of cisplatin (20 mg/m(2),IV) when given in weekly doses prior to localized irradiation in dogs with solid malignancies. Eleven dogs received a total of 54 weekly doses of cisplatin. Two dogs did not complete the 5-week protocol due to progressive disease and two dogs received 6 weekly doses of cisplatin. Repeated administration of cisplatin caused a significant decline in the leukocyte count, segmented neutrophil count, and platelet count. These changes were related to the number of cisplatin doses. The dogs did not have any significant alteration of blood urea nitrogen, serum creatinine, or urine specific gravity during the treatment period. Weekly low-dose cisplatin, as used in this study, is safe for use in tumor-bearing dogs. However, the significant decline in the leukocyte, segmented neutrophil, and platelet counts in these 11 dogs suggest that cisplatin prescribed at 20 mg/m(2) IV once per week should not exceed five consecutive treatments.  相似文献   

6.
Cisplatin Therapy in 41 Dogs With Malignant Tumors   总被引：3，自引：0，他引：3  
Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).  相似文献   

8.
OBJECTIVE: To evaluate the effect of saline (0.9% NaCl) solution administered IV to induce diuresis on 15 dimensional variables of the kidneys, size of renal pelvis, and diameter of the cranial part of the ureters. ANIMALS: 25 dogs without evidence of renal disease that were undergoing chemotherapy for various neoplasms. PROCEDURE: The kidneys, cranial aspect of the ureters, and trigone area of the urinary bladder of each dog were examined ultrasonographically before and during IV administration of saline solution (2.7 to 18.8 ml/kg of body weight/h). RESULTS: Ultrasonography revealed unilateral and bilateral pyelectasis during diuresis in 16 of 23 (70%) dogs but unilateral pyelectasis in only 1 dog before diuresis. Unilateral pyelectasis during diuresis was observed in 11 of 16 (69%) dogs. Pyelectasis during diuresis was categorized as slight in 15 of 21 (71%) kidneys. Degree of pyelectasis during diuresis was not identical in both kidneys of 13 of 16 (81 %) dogs. Diuresis did not induce ureterectasis, and it did not cause changes in 15 dimensional variables of the kidneys. CONCLUSIONS: In nonsedated, nonazotemic dogs, IV administration of saline solution to induce diuresis may cause slight pyelectasis without evidence of ureterectasis. CLINICAL RELEVANCE: When dilatation of the cranial part of the ureter is > 2 mm at the same time that ipsilateral pyelectasis is detected during ultrasonographic examination of the urinary tract system of a nonsedated, nonazotemic dog receiving IV administration of saline solution to induce diuresis, additional examinations are recommended to determine the possibility of early obstructive nephropathy or pyelonephritis.  相似文献   

9.

Background

Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.

Hypothesis/Objectives

We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.

Animals

Fourteen client‐owned dogs were prospectively enrolled.

Methods

Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.

Results

A 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).

Conclusions and Clinical Importance

Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.  相似文献   

10.
Cisplatin Toxicity in Cats   总被引：2，自引：1，他引：1  
Cisplatin (cis-diamminedichloroplatinum; Platinol, Bristol, Syracuse, NY) was administered to 11 cats, divided into three groups of experimental and clinical patients. In group 1, cisplatin was administered at a dose of 60 mg/m2 to four cats. In an attempt to avoid renal toxicity, saline diuresis was induced by administering 0.9% saline solution intravenously at a rate of 20 ml/kg/hr for 4 hours before and 2 hours after cisplatin administration. All four cats became dyspneic and died 48-96 hours after cisplatin administration. Postmortem findings included severe hydrothorax, pulmonary edema, and mediastinal edema. In group 2, four experimental cats entered a trial comparing the effects of saline diuresis and cisplatin (60 mg/m2) with the effects of saline diuresis and placebo (0.9% saline solution). The cats in the saline control group remained completely normal, while the cats that received cisplatin developed clinical signs and gross postmortem pulmonary changes identical to those in the first group of cats. Histopathologic examination showed that the alveolar septa were thickened and congested, and contained macrophages, occasional neutrophils, thrombi, and small foci of necrosis and fibrin. Microangiopathic changes were seen in the alveolar capillaries. In the third group, three additional cats were treated with a lower dose of cisplatin. Two cats that received 40 mg/m2 of cisplatin developed pulmonary changes similar to, but less severe than, those seen in the cats that received the higher dose of cisplatin. One cat treated with 20 mg/m2 of cisplatin showed no pulmonary changes ante mortem or post mortem. This series of 11 clinical and experimental cases identifies an apparent species-specific, dose-related, primary pulmonary toxicity of cisplatin in cats.  相似文献   

11.
OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of morphine after IV administration as an infusion or multiple doses in dogs by use of a von Frey (vF) device. ANIMALS: 6 dogs. PROCEDURE: In the first 2 crossover experiments of a 3-way crossover study, morphine or saline (0.9%) solution was administered via IV infusion. Loading doses and infusion rates were administered to attain targeted plasma concentrations of 10, 20, 30, and 40 ng/mL. In the third experiment, morphine (0.5 mg/kg) was administered IV every 2 hours for 3 doses. The vF thresholds were measured hourly for 8 hours. Plasma concentrations of morphine were measured by high-pressure liquid chromatography. RESULTS: No significant changes in vF thresholds were observed during infusion of saline solution. The vF thresholds were significantly increased from 5 to 8 hours during the infusion phase, corresponding to targeted morphine plasma concentrations > 30 ng/mL and infusion rates > or = 0.15 +/- 0.02 mg/kg/h.The maximal effect (EMAX) was 78 +/- 11% (percentage change from baseline), and the effective concentration to attain a 50% maximal response (EC50) was 29.5 +/- 5.4 ng/mL. The vF thresholds were significantly increased from 1 to 7 hours during the multiple-dose phase; the EC50 and EMAX were 23.9 +/- 4.7 ng/mL and 173 +/- 58%, respectively. No significant differences in half-life, volume of distribution, or clearance between the first and last dose of morphine were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered via IV infusion (0.15 +/- 0.02 mg/kg/h) and multiple doses (0.5 mg/kg, IV, every 2 hours for 3 doses) maintained significant antinociception in dogs.  相似文献   

12.
Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

13.
Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
OBJECTIVE: To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURES: In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS: Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.  相似文献   

15.
Cytosine arabinoside (AraC) was administered as a continuous IV infusion to 15 dogs with malignant lymphoma at a dose of 300 mg/m2/d for 2 consecutive days. Dogs were re-examined 7 d after treatment for response to therapy and for hematologic toxicity. Regardless of response, all dogs were started on combination chemotherapy at this time. Other toxicities were reported by owners. No dog responded objectively to Ara-C treatment, although 1 dog with circulating lymphoblasts had partial regression of lymphadenopathy but persistent blastemia. Thrombocytopenia (platelet count < 200,000/μL) 7 days posttreatment was the most commonly encountered hematologic toxicity, occurring in 10 of 14 dogs. Three of these 10 dogs were also mildly neutropenic (neutrophil counts of 2000 to 3000 cell/μL). Nonhematologic toxicity occurred in 8 of 15 dogs and was principally gastrointestinal in nature and mild in severity. Cytosine arabinoside at a dose of 300 mg/m2/day was not considered an active drug for the induction of remission in dogs with lymphoma.  相似文献   

16.
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.  相似文献   

17.
Reversal of Oxymorphone Sedation by Naloxone, Nalmefene, and Butorphanol   总被引：1，自引：0，他引：1  
The effects of naloxone (0.4 mg and 1.2 mg intravenously [IV]), nalmefene (0.03 mg/kg IV) and butorphanol (0.2 mg/kg IV and 0.4 mg/kg IV) on oxymorphone-induced sedation were studied in six dogs over a 4-hour observation period. The same dogs were observed for 4 hours untreated (unsedated control) and with oxymorphone sedation followed by saline solution (sedated control). The reversal drug or saline placebo was administered IV 20 minutes after oxymorphone (4.5 mg IV). Blinded observers evaluated the dogs for positional and attitudinal responses, heart rate, and respiratory rate. Sedated dogs treated with nalmefene most closely resembled unsedated dogs in all observed variables. Naloxone was most effective when administered at the higher dose. Mild renarcotization occurred in two dogs at hour 2, even after the higher naloxone dose. Residual sedation was observed in all dogs treated with 0.4 mg naloxone. Butorphanol resulted in partial reversal of sedation at both dosage levels. However, the degree of sedation was significantly less than that observed in the saline-treated controls, and it appeared that 0.4 mg/kg butorphanol may be clinically useful for opiate reversal in some situations.  相似文献   

18.
The purpose of the study was to evaluate the effect of preoperative administration of meloxicam, a non-steroidal anti-inflammatory drug used for pain control, on primary haemostasis in dogs. Twenty healthy female dogs undergoing elective ovariohysterectomy were enrolled in the study. Sixty minutes before pre-anaesthesia, a single dose of meloxicam (0.2 mg/kg) was randomly administered intravenously (IV) to 10 dogs (treatment group) while control dogs received an equivalent volume of saline solution IV. Platelet aggregation, buccal mucosa bleeding time, platelet count and haematological indices were measured at 0, 1, 6 and 24 h after administration of meloxicam. Since significant differences between groups were not observed for any of the measured parameters, preoperative administration of meloxicam may be used for pain control before elective ovariohysterectomy in healthy dogs, without compromising primary haemostasis.  相似文献   

19.
OBJECTIVE: To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS). ANIMALS: 27 cats with a nonresectable, recurrent, or metastatic VAS. PROCEDURE: Each cat received ifosfamide (900 mg/m(2) of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifosfamide-associated toxic effects were graded in accordance with predetermined criteria. RESULTS: 61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treatments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/muL (range, 200 to 5,382 cells/microL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis. CONCLUSIONS AND CLINICAL RELEVANCE: Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.  相似文献   

20.
OBJECTIVE: To evaluate the efficacy of maropitant, a novel neurokinin-1 receptor antagonist, to treat and prevent emesis caused by IV infusion of a chemotherapeutic dose of cisplatin (70 mg/m(2)) in dogs. ANIMALS: 64 healthy 6-month-old Beagles (32 males and 32 females). PROCEDURES: To evaluate the effect of maropitant on ongoing emesis, 24 dogs were randomized to 2 treatment groups (12 dogs each). Saline (0.9% NaCl) solution or maropitant (1 mg/kg) was administered once by SC injection immediately following the first emetic event after cisplatin infusion. Dogs were assessed for emesis for 6 hours after initiation of cisplatin infusion. To evaluate the use of maropitant for the prevention of emesis, 40 dogs were randomized to 4 treatment groups (10 dogs each). Placebo or maropitant (1, 2, or 3 mg/kg) was administered PO as a tablet. Cisplatin infusion was initiated at 19 hours after treatment, and dogs were assessed for emesis for 6 hours. RESULTS: No treatment-related adverse events were observed in either study. For the treatment of ongoing emesis, significantly fewer emetic events were observed for maropitant-treated dogs, compared with placebo-treated dogs (mean, 5.2 vs 15.8), and the mean time to cessation of emesis was significantly shorter (0.65 vs 1.65 hours). In the prevention of emesis, maropitant-treated dogs had significantly fewer emetic events (means, 2.7, 1.1, and 0.5 for maropitant at 1, 2, and 3 mg/kg, respectively), compared with placebo-treated dogs (mean, 20.3). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that maropitant is safe and effective in the treatment and prevention of cisplatin-induced emesis in dogs.  相似文献   

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