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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.
OBJECTIVE: To determine the effect of long-term administration of enalapril on renal function in dogs with severe, compensated mitral regurgitation. DESIGN: Randomized controlled trial. ANIMALS: 139 dogs with mitral regurgitation but without overt signs of heart failure. PROCEDURE: Dogs were randomly assigned to be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and serum creatinine and urea nitrogen concentrations were measured at regular intervals for up to 26 months. RESULTS: Adequate information on renal function was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median, 12 months). Mean serum creatinine and urea nitrogen concentrations were not significantly different between dogs receiving enalapril and dogs receiving the placebo at any time, nor were concentrations significantly different from baseline concentrations. Proportions of dogs that developed azotemia or that had a +/- 35% increase in serum creatinine or urea nitrogen concentration were also not significantly different between groups. Conclusions: And Clinical Relevance: Results suggest that administration of enalapril for up to 2 years did not have any demonstrable adverse effects on renal function in dogs with severe, compensated mitral regurgitation.  相似文献   

4.
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   

5.
The feasibility of renal arterial infusion of nonbiodegradable microspheres as a model of chronic renal disease in dogs was evaluated. Resin-coated, styrene-divinyl benzene copolymer microspheres were infused into the kidneys of healthy adult Beagles by direct injections of both renal arteries in a single surgical procedure. Injections of 25-microns diameter microspheres had minimal effect on either the clinical status or serum values of the dogs. Histologic examination revealed the majority of the microspheres lodged within the capillary beds of the glomeruli, and little change to the kidneys. However, injections of 50-microns diameter microspheres caused significant increases in serum concentrations of urea nitrogen and creatinine. Histologically, the larger microspheres obstructed afferent arterioles and small arteries, which caused diffuse glomerular necrosis and nephron damage. With doses ranging from 1 to 3 million microspheres/dog, a correlation between the quantity of microspheres injected and severity of renal damage was observed. The optimal dose for producing a model of moderate renal disease was determined to be 1.8 million microspheres/dog (0.9 million microspheres/kidney). During long-term studies, microsphere-injected dogs fed a moderately restricted protein ration remained relatively azotemic, compared with control dogs on the identical ration. During the 5-month postsurgical period, the serum urea nitrogen concentration averaged 18.41 +/- 1.59 mg/dl (mean +/- SE) for the microsphere-injected dogs vs 9.31 +/- 0.38 for the control dogs (P less than 0.001). Similarly, the mean serum creatinine value was significantly higher (P = 0.020) for the microsphere-injected dogs, compared with the controls (1.23 +/- 0.12 mg/dl vs 0.94 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

6.
Hemolytic Uremic Syndrome in Dogs   总被引：1，自引：1，他引：0  
A disease syndrome similar to the hemolytic uremic syndrome of people is described in three dogs with acute renal failure. In each dog, hemorrhagic gastroenteritis preceded the onset of anuric acute renal failure. Evidence of microangiopathic hemolytic anemia (schizocytes, thrombocytopenia, and increased concentrations of fibrin split products) was present in the three dogs. Serum chemistry results showed increased concentrations of blood urea nitrogen, creatinine, and phosphorus. Ultrasound examination performed in one dog revealed increased echogenicity of the renal cortices. Treatment for anuric acute renal failure using a continuous dopamine and furosemide infusion established urine production in one of three dogs. Microscopic examination of tissue from the two dogs that underwent necropsy showed occlusion of the renal vasculature by fibrin thrombi consistent with microangiopathic arteriolar thrombosis. The pathophysiology and current knowledge of human hemolytic uremic syndrome is compared with hemolytic uremic syndrome in these dogs. (Journal of Veterinary Internal Medicine 1993; 7:220–227. Copyright © 1993 by the American College of Veterinary Internal Medicine.)  相似文献   

7.
Glomerulonephritis (GN) is a leading cause of chronic renal failure in dogs. However, little is known about the efficacy of available treatment options for GN in this species. The purpose of this study was to determine the effects of cyclosporine (Cy) administration on the outcome of naturally occurring GN in dogs. Thirteen dogs from 4 institutions were included in the study. Randomization of dogs into placeboversus Cy-treated groups was stratified according to initial morphological diagnosis and contributing institution. Seven and 6 dogs were assigned to be given placebo or Cy, respectively. The initial Cy dose of 10 mg/kg every 24 hours was adjusted to maintain 24-hour trough, whole blood Cy concentrations between 250 and 400 ng/mL. There were no statistically significant differences between placebo-and Cy-treated groups with respect to serum total protein, albumin, urea nitrogen and creatinine, and plasma protein concentrations; platelet count; urine protein-creatinine ratio; endogenous creatinine clearance; 24-hour urine protein concentrations; or 24-hour urine protein—endogenous creatinine clearance ratio. However, PCV was significantly lower in the Cy-treated group. Decreased appetite, diarrhea, vomiting, weight loss, involuntary shaking, and thrombocytopenia were noted in both treatment groups; however, clinical signs in Cy-treated dogs subjectively were more severe. One Cy-treated dog developed gingival hyperplasia. After entry into the study, the median survival times for placebo-and Cy-treated dogs were 16 and 11 months, respectively. Considering the expense and the frequency of adverse effects related to Cy administration, the use of Cy in the treatment of dogs with GN does not seem warranted.  相似文献   

8.
OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.  相似文献   

9.
OBJECTIVES: To evaluate renal function in healthy dogs undergoing general anesthesia and ovariohysterectomy without concurrent IV administration of fluids. ANIMALS: 35 healthy client-owned dogs. PROCEDURE: Dogs were medicated with promazine hydrochloride (0.05 mg/kg of body weight, SC) approximately 45 minutes before induction of anesthesia with thiopental sodium (10 to 15 mg/kg, IV). Anesthesia was maintained with 2% halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students under the direct supervision of a veterinary surgeon. Renal function was assessed (serum urea and creatinine concentrations, fractional clearance of sodium, urine alkaline phosphatase [ALP] and gamma-glutamyltransferase [GGT] activities, urine specific gravity, and enumeration of renal tubular epithelial cells in urine sediment) prior to and 24 and 48 hours after surgery. RESULTS: Duration of general anesthesia ranged from 80 to 310 minutes. Urine specific gravity and ALP activity and serum urea and creatinine concentrations did not change over time. Fractional clearance of sodium decreased 24 and 48 hours after surgery, whereas urine GGT activity and the ratio of urine GGT activity to urine creatinine concentration increased 24 hours after surgery, compared with presurgery values. Renal tubular epithelial cells increased in number in urine sediment from 11 of 35 (31.4%) dogs and 5 of 35 (14.3%) dogs 24 and 48 hours after surgery, respectively. However, this increase was not clinically relevant. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fluids to healthy dogs undergoing general anesthesia and elective surgery may not be necessary for maintenance of renal homeostasis.  相似文献   

10.
Captopril, furosemide, and a sodium-restricted diet were administered to 6 normal dogs and 10 dogs with congestive heart failure. Serum electrolyte concentrations and renal function were monitored in both groups. In the normal dogs, no clinically meaningful changes in serum electrolyte, urea nitrogen, or creatinine concentrations developed during therapy with a sodium-restricted diet and 4 weeks each of furosemide alone, captopril alone, or furosemide plus captopril. Three of 6 normal dogs on furosemide and a sodium-restricted diet had at least one serum potassium concentration above the reference range during the 4 weeks of observation. One normal dog on captopril, furosemide, and a sodium-restricted diet developed azotemia, and 2 dogs had serum potassium concentrations above the reference range during the 4 weeks of observation. Ten dogs with congestive heart failure were treated with captopril, furosemide, a sodium-restricted diet, and digoxin.
Etiopathogenesis of the heart failure included valvular insufficiency (n = 6), dilated cardiomyopathy (n = 3), and dilated cardiomyopathy and dirofilariasis (n = 1). Serum electrolyte concentrations and renal function were monitored for 5 consecutive weeks in 7 of the 10 dogs and for 17 weeks or longer in 6. Two dogs were euthanized after 4 weeks because of acute decompensation of heart failure, and one dog developed severe azotemia and uremia. Six of 10 dogs with congestive heart failure had at least one serum potassium concentration above the reference range sometime during the 5 weeks of observation, although the changes in the mean serum potassium concentrations were not statistically significant. Four of 10 dogs with congestive heart failure developed azotemia sometime during the 5 weeks of observation.  相似文献   

11.
OBJECTIVE: To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months. DESIGN: Prospective, randomized, blinded, placebo-controlled clinical trial. ANIMALS: 22 dogs with osteoarthritis in the hip or elbow joint. PROCEDURE: 13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, gamma-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects. RESULTS: Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.  相似文献   

12.
The records of 15 sequential cases of transitional cell carcinoma of the urinary bladder or urethra in dogs were examined to determine the results of treatment with cisplatin (cisdiamminedichloroplatinum) and to record and assess toxicities. All dogs had measurable disease and were considered eligible for evaluation of toxicity following one cisplatin treatment. Three dogs were eliminated from evaluation of efficacy because of acute toxicities. Of the 12 remaining dogs that received two or more cisplatin treatments, evaluations at the end of the second month of treatment revealed no complete responses; however, three dogs showed partial responses and six dogs maintained stable disease. Three dogs had tumor progression. The median survival time for these 12 dogs was 180 days (mean, 220 days; range, 36 to 589 days). Three dogs were azotemic before treatment. Two of these dogs showed improvement in renal function following therapy. Six of the other twelve dogs developed increases in serum creatinine during therapy. The objective and subjective improvements of some dogs to cisplatin chemotherapy suggest that this agent is active in selected dogs with transitional cell carcinomas of the urinary tract.  相似文献   

13.
In this study the pharmacokinetics and renal safety of gentamicin in healthy dogs was investigated after multiple dosing. Six adult male dogs received once-daily gentamicin (6 mg/kg) intramuscularly for 5 days. Serial blood samples were taken on days 1 and 5 of treatment, and at predose, 1 and 6 h on days 2, 3 and 4. Urinalysis, hematology and serum biochemistry evaluation were carried out before, 7 and 14 days after the first gentamicin administration. Mean value of the main pharmacokinetic parameters were: AUC (microg.h/mL), 97.4 and 100.2; terminal half-life (harmonic mean), 0.76 and 1.01 h; ClB/F (mL/min.kg), 1.24 and 1.10; VD(area)/F (L/kg), 0.084 and 0.10; MRT (h), 1.48 and 1.77; Cmax (microg/mL), 54.5 and 49.2; tmax (h), 0.40 and 0.48 for the first and last dose, respectively. Accumulation was determined as R1 = 0.97 and R2 = 1.22. Mean trough gentamicin serum concentrations were 0.06, 0.07, 0.09, 0.1 and 0.1 microg/mL for the first, second, third, fourth and fifth dose, respectively. Statistically significant increases (P < 0.05) were found for last dose MRT and fourth and fifth trough gentamicin serum concentrations. Laboratory tests detected a slight increase in serum creatinine and urea nitrogen concentrations (one dog), decreased specific urine gravity (one dog) and presence of few granular casts (two dogs). It is concluded that once-daily administration of gentamicin may provide adequate serum levels to treat most susceptible gram-negative infections with little or no nephrotoxicity in dogs.  相似文献   

14.
Azotemic dogs receiving prednisone and azathioprine to enhance renal allograft survival had higher blood urea nitrogen (BUN):serum creatinine (SC) ratios, when compared with nontreated dogs with induced azotemia. The difference in ratios probably was attributable to increased BUN content secondary to the catabolic effects of the drugs used. However, dogs with naturally occurring renal failure had BUN:SC ratios that were similar to those for dogs receiving the catabolic drugs. It was concluded that even though catabolic drugs may influence BUN:SC ratios, the multiplicity of other factors affecting BUN and SC may interact to cause a wide range of BUN:SC ratios under conditions of naturally occurring primary renal failure in the dog.  相似文献   

15.
Uremic gastritis is a term commonly used to describe the gastrointestinal signs and histopathologic changes associated with renal failure in the dog. This retrospective study reviews the clinical, serum biochemical, and postmortem histopathologic data from 28 dogs with renal failure to determine the prevalence of gastric histopathology, characterize the gastric histopathology, and identify associations between gastric histopathology and serum concentrations of blood urea nitrogen (BUN), creatinine (Cr), calcium-phosphorus product (Ca x Phos), and hematocrit. Affected and control dogs with available renal and gastric tissue, serum biochemistry data, and urinalysis data were identified over a 10-year period (1992-2002) in the pathology department postmortem examination database at the Cornell University College of Veterinary Medicine. The serum biochemistry data and histopathologic findings were scored as normal, mild, moderate, and severe. All affected dogs had derangements of BUN, Cr, or Ca x Phos with gastric histopathology in 22 of 28 dogs (79%). Dogs with renal failure had a higher prevalence of gastric histopathologic changes compared with the control group. Associated histopathologic changes in the stomach were edema (P = .008), mineralization (P = .03), and vasculopathy (P = .03). Only 1 dog had evidence of gastric ulceration. Gastric necrosis was an uncommon finding (4/28, 14%). Gastric histopathology appears to be common in dogs with renal failure and is associated with increasing severity in the serum biochemistry data. Unlike humans with renal failure, in whom gastric ulceration predominates, gastric necrosis and ulceration appear to be uncommon in dogs with renal failure.  相似文献   

16.
The purpose of this study was to evaluate the clinical safety of pamidronate when administered at a mean dosage of 1.0 mg/kg IV q28d in 33 tumor-bearing dogs. Biochemical tests of renal function were evaluated before each successive pamidronate treatment. Of 33 dogs treated with pamidronate, 1 dog had clinically relevant increases in serum creatinine and blood urea nitrogen concentrations. The biologic activity of IV pamidronate was assessed prospectively in 10 dogs with appendicular osteosarcoma and was assessed on reductions in urine N-telopeptide excretion (P = .042) and enhanced bone mineral density of the primary tumor measured with dual-energy x-ray absorptiometry (P = .024). Additionally, in these 10 dogs, pamidronate's therapeutic activity was supported by subjective improvement in pain control in 4 of the 10 dogs treated. IV pamidronate appears clinically safe in tumor-bearing dogs and may possess modest biologic activity for managing neoplastic complications associated with pathologic bone resorption.  相似文献   

17.
Thirteen dogs with tumors were treated with monthly infusions of cisplatin. Complete responses were not observed. Of 8 dogs with urinary tract transitional cell carcinomas, 1 (12.5%) had a partial response of 31 weeks' duration, and 4 (50%) had stable disease for 12, 30, 32, and 34 weeks. Three (60%) of 5 dogs with head and neck squamous cell carcinomas had partial responses for 2, 10, and 15 weeks. All 13 dogs were evaluated for signs of toxicosis. Transient episodes of vomiting were recorded for 7 dogs (54%), and 2 dogs (15%) had mild thrombocytopenia. Although renal function gradually decreased in 2 dogs (15%), none of the dogs had an episode of acute renal failure attributable to cisplatin. These findings suggest that cisplatin may be a safe and potentially effective agent for treatment of transitional cell and squamous cell carcinomas in dogs.  相似文献   

18.
OBJECTIVE: To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine. ANIMALS: 6 male and 6 female healthy young-adult Beagles. PROCEDURE: A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia. RESULTS: Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.  相似文献   

19.
Serum Cystatin C (sCys-C) is one of the most important serum markers of renal function assessment in dogs. The purpose of this study was to determine the sCys-C concentration in dogs with visceral leishmaniasis (VL). In the study, 16 dogs with VL and 10 clinical healty dogs (control) were used. Mean sCys-C concentration of the infected dogs was significantly higher than that of the control group (p < 0.05). Mean serum creatinine concentration was lower and mean blood urea nitrogen, albumin and globulin concentrations were higher in dogs with VL; however, these changes were not statistically significant. Mean total protein and phosphorus concentrations were found to be higher in dogs with VL than healthy dogs (p < 0.05). No significant correlation had been determined between sCys-C and other variables. Visceral leishmaniasis in dogs has increased sCys-C concentration indicating a possible renal impairment; however, further studies are needed to be performed together with renal biopsies in the investigation sCys-C in dogs with VL.  相似文献   

20.
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   

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