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Biomedical subjects

D M Boothe

Publications and source records attributed to D M Boothe.

At least 37 records · Page 2Linked to original sources
PubMed1997

Itraconazole disposition after single oral and intravenous and multiple oral dosing in healthy cats.

OBJECTIVE: To determine the disposition of itraconazole in cats after single IV and oral dosing (as a solution or capsule) and multiple oral (capsule) dosing, and to establish bioavailability after oral administration of the solution. ANIMALS: 6 healthy cats for experiment 1 (E1), and 12 cats for experiment 2 (E2). PROCEDURE: For E1 (nonrandomized crossover design), each cat received a single dose of itraconazole solution (5 mg/kg of body weight) orally, and 1 month later, another dose i.v.. Blood samples were collected for 96 hours. For E2, each cat was given either 5 (group [G] 1) or 10 (G2) mg of itraconazole/kg (capsules) twice daily for 6 weeks. Samples were collected for 96 hours after the first and last dose. Itraconazole was detected by use of high-performance liquid chromatography. RESULTS: For E1, itraconazole plasma drug concentration extrapolated to time zero (IV dose) was 5.2 +/- 1.4 micrograms/ml, and mean residence time (MRT) was 37 +/- 16 hours. For oral dosing, maximal itraconazole concentration was 1.69 +/- 0.864 micrograms/ml, MRT was 48 +/- 17 hours, and bioavailability was 78.8 +/- 28%. For the multiple oral dosing study, MRT (at last dose: 81.1 +/- 97.4 hours for G1, and 63.1 +/- 15.1 hours for G2) was shorter (P = 0.02) at first dose, compared with last dose, for both groups but did not differ between groups. Maximal concentration did not differ between groups at either time. Steady state was achieved at 14 to 21 days. All cats tolerated itraconazole with no evidence of adverse effects. CONCLUSIONS: The oral itraconazole solution is preferred to capsules; a 24-hour dosing interval should be sufficient; 10 mg/kg given daily should generate therapeutic concentrations in most cats; steady-state concentrations may take up to 3 weeks to achieve; and cats appear to tolerate itraconazole well.

Administration, Oral↗
PubMed1996

Effects of serum separation tubes on serum benzodiazepine and phenobarbital concentrations in clinically normal and epileptic dogs.

OBJECTIVE: To characterize the effects of serum separation tubes (SST) on serum drug concentrations. SAMPLE POPULATION: Clinically normal dogs (clorazepate, n = 7) or dogs with epilepsy (phenobarbital, n = 7) were studied in experiment 1, and samples submitted for therapeutic drug monitoring (n = 87) were studied in experiment 2. PROCEDURE: In experiment 1, blood containing either drug was placed in 2 types of 4-ml SST (SST-A and SST-B) and in nonserum separation tubes (non-SST [control]). Samples were processed, then stored at 20 to 22 C (both drugs) or 10 C (phenobarbital only). Aliquots were collected for 96 hours. The rate constant of disappearance and the percentage decrease of each drug over time were determined for each tube. For experiment 2, paired samples were collected in non-SST and SST and submitted by mail for therapeutic drug monitoring. The SST samples were either decanted from SST prior to shipment (group 1; n = 30) or mailed in SST with serum in contact with the silica gel (group 2; n = 57). Drug concentrations and drug elimination half-life were compared between groups. For both experiments, drugs were detected in samples, using polarized immunofluorescence. RESULTS: For experiment 1, the rate constant of drug disappearance for both drugs was greater in the 4-ml SST-A (P < 0.0001). This SST also caused the greatest percentage decrease (20% for phenobarbital and 35% for benzodiazepines) at 96 hours. Refrigeration reduced the mean decrease in phenobarbital at 96 hours to 11%. For experiment 2, phenobarbital concentration was lower for both SST, compared with non-SST (P < 0.0005). Phenobabital had decreased a mean 6.4 +/- 0.5% in group-1 and a mean 30.5 +/- 11.1% in group-2 (P < 0.0005) samples. CONCLUSION: The SST should be avoided when collecting serum for monitoring of either phenobarbital or benzodiazepines. CLINICAL RELEVANCE: The SST can falsely decrease serum drug concentrations and should be avoided when collecting blood for therapeutic drug monitoring.

Animals↗
PubMed1994

Nephrotoxicosis associated with topical administration of gentamicin in a cat.

A 4-year-old cat was referred for treatment of a large, open wound. The wound had been lavaged twice, approximately 12 hours apart, with approximately 10 ml of 5% gentamicin solution prior to referral, because of infection caused by Pseudomonas spp. Results of initial serum biochemical analyses were within reference ranges, and the cat was anesthetized for surgical wound debridement and closure. Two days later, the cat was azotemic (SUN concentration, 113 mg/dl; serum creatinine, concentration, 9.8 mg/dl) and had a urine specific gravity of 1.008. Granular casts were seen in the urine. The azotemia became more severe over the next 2 1/4 hours, despite treatment for acute renal failure, and the cat was euthanatized. Severe acute proximal tubular necrosis, consistent with gentamicin-induced nephrotoxicosis, was diagnosed histologically. Retrospectively, serum samples obtained for biochemical analyses were assayed for gentamicin concentration. Serum concentration of gentamicin 8 hours after topical lavage was 58.07 micrograms/ml. This was approximately 6 times greater than the desired peak concentration for gentamicin and suggested that gentamicin had been absorbed systemically following topical application.

Abscess↗
PubMed1994

Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease.

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P < or = 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.

Analysis of Variance↗
PubMed1993

Effects of vena caval banding in experimentally induced multiple portosystemic shunts in dogs.

Effects of vena caval banding on portal venous and vena caval hemodynamics were examined in 6 control dogs and in 10 dogs that had undergone attenuation (banding) of the abdominal part of the caudal vena cava and had dimethylnitrosamine-induced multiple portosystemic shunts (PSS). Additionally, indocyanine green (ICG) extraction and clearance after infusion to steady state were used to calculate hepatic plasma flow in these dogs. Sixteen dogs were randomly assigned to 2 groups: control (n = 6) or diseased (n = 10). Diseased dogs were administered dimethylnitrosamine (2 mg/kg, PO, twice weekly) until multiple PSS developed, as assessed by results of clinical laboratory tests, ultrasonography, and hepatic scintigraphy. Shunts were confirmed visually at celiotomy and by contrast portography. Venous pressures (caudal vena caval, portal, and hepatic) were recorded before and after vena caval banding for up to 7 days in dogs from both groups. Peritoneal cavity pressures were recorded in all dogs after closure of the body wall. To determine ICG extraction and clearance, a bolus injection of ICG (0.5 mg/kg, i.v.) was administered, followed by steady-state infusion of 0.097 mg/min. Extractions and clearances of ICG were measured, and from these, hepatic plasma flow rates were determined immediately before and after banding and at 6 hours, 48 hours, and 7 days after banding. The gradient (caudal vena caval pressure within 1 to 2 mm of Hg of portal pressure) between caudal vena cava and portal venous pressures established at banding was maintained after the first hour in both groups. Caudal vena cava pressures established at banding were maintained throughout the study, with the exception of the first hour in diseased dogs. Extraction ratios were higher in control dogs at all times, except at 48 hours. Clearance was higher in control dogs at all times. Hepatic plasma flow did not differ between groups, except immediately after banding, when flow was greater in diseased dogs, and differences were not found over time in either group. This study indicated that vena caval banding in this model of experimentally induced multiple PSS increases and maintains caudal vena cava pressure, relative to portal venous pressure (after the first hour) for 7 days, and that calculated hepatic plasma flow is not persistently improved by vena caval banding.

Animals↗
PubMed1993

Tracheal mucociliary transport rate in awake dogs.

To measure tracheal mucociliary transport rate (TMTR) in awake dogs, restrained in dorsal recumbency, 99mtechnetium-labeled macroaggregated albumin was administered by tracheal injection, and the cephalic movement of boluses containing the radiopharmaceutical was detected by a gamma camera positioned lateral to the dog's head and neck. The distance traveled by each bolus was measured, relative to external markers placed a known distance apart. Tracheal mucociliary transport rates were calculated by dividing the measured distance of radiopharmaceutical movement by elapsed time. The technique was efficient and well tolerated. Mean (+/- SD) TMTR was 35.3 +/- 15.9 mm/min. Significant (P = 0.029) difference in TMTR was found between males and females, but significant difference attributable to age of the dog was not detected. This method of measuring TMTR in awake dogs has potential for evaluation of clinical animal patients with suspected tracheal mucociliary abnormalities.

Aerosols↗
PubMed1992

Use of hepatobiliary scintigraphy in the diagnosis of extrahepatic biliary obstruction in dogs and cats: 25 cases (1982-1989).

Twenty-five animals (21 dogs and 4 cats) in which hepatobiliary scintigraphy (HBS) was performed between 1982 and 1989 were included in a retrospective study to determine the utility of HBS for diagnosis of extrahepatic biliary obstruction. Final diagnoses, which were based on liver biopsy results and surgical findings in all animals, were hepatocellular disease alone (n = 17), hepatocellular disease and extrahepatic biliary obstruction (n = 7), and normal liver (n = 1). Hepatobiliary scintigraphy was performed by use of 99mTc-diisopropyl iminodiacetic acid in all cases. All 7 cases of extrahepatic biliary obstruction were confirmed at surgery. In animals with biliary obstruction, HBS failed to demonstrate radiolabel within either the gallbladder or intestine at any time. Using nonvisualization of the intestine by 180 minutes as the scintigraphic criterion for diagnosis of biliary obstruction, sensitivity was 83% and specificity was 94% in this series. Hepatobiliary scintigraphy was concluded to be an accurate indicator of extrahepatic biliary obstruction in this group of animals. High serum bilirubin concentration at the time HBS was performed did not appear to reduce the diagnostic usefulness of the scintigraphic findings.

Animals↗
PubMed1992

Respiratory therapeutics.

Treatment of small animal respiratory diseases tends to target bronchodilators. Although this is not inappropriate, recent advances in the understanding of respiratory diseases have underscored the importance of inflammatory mediators in the pathophysiology of respiratory diseases. Drug therapy of the respiratory tract in small animals is most successful when it is based on a knowledge of normal physiology and disease pathophysiology of respiratory tract diseases.

Animals↗
PubMed1992

Indocyanine green disposition in healthy dogs and dogs with mild, moderate, or severe dimethylnitrosamine-induced hepatic disease.

Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease.

Animals↗
PubMed1992

Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease.

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.

Animals↗
PubMed1990

Drug therapy in cats: recommended dosing regimens.

The goal of this series of articles has been to provide a comprehensive review of the literature regarding recommended dosing regimens, therapeutic indications and contraindications, and potential side effects of drugs used in cats. In this fourth and last article, the available information regarding dosage regimens in cats has been consolidated in tabular form to facilitate an effective and rational approach to the pharmacologic prevention and treatment of a variety of feline medical disorders.

Animals↗
PubMed1990

Drug therapy in cats: a therapeutic category approach.

The third article of this 4-part series discusses drug therapy in cats by therapeutic category. Specifically, the use of drugs to control infections, pain, fever, inflammation, cancer, and selected parasites is described. In addition, the use of hormonally related drugs and selected miscellaneous drugs in cats is addressed. Drugs emphasized are those for which use in cats is frequently associated with adverse reactions or drugs for which use is limited to illnesses that tend to be unique in cats.

Animals↗