Multidose pharmacokinetics and safety of a modified, compounded theophylline product in dogs.

Theophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species-validated commercial products are available. This study reports the single-dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well-established, USP-compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 µg/ml for 91 +/- 15% of the dosing interval. There was no significant difference in half-life between single-dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.

Biomechanical properties of canine staphylectomies closed with barbed or smooth suture.

OBJECTIVE: To compare the duration of closure and biomechanical properties of staphylectomies closed with absorbable bidirectional barbed suture or smooth monofilament suture in a simple continuous or interrupted pattern STUDY DESIGN: Ex vivo study SAMPLE POPULATION: Soft palates (n = 60) harvested from mesaticephalic canine cadavers METHODS: One centimeter of tissue was excised from the caudal border of each soft palate, and the oral and nasopharyngeal mucosal surfaces were apposed with 2-0 bidirectional Quill Monoderm knotless closure device barbed suture (Q), 3-0 Monocryl in a simple continuous (MC) pattern, or 3-0 Monocryl in a simple interrupted (MI) pattern (n = 20 per group). Duration of closure was compared between groups. Tissues were tested under tension to failure, and mode of failure data were collected by video capture. RESULTS: Closure time was longer for MI closures than for Q and MC closures, with means of 259.9, 215.4, and 196.7 seconds, respectively (P < .0001). No difference was detected in yield force, force to first tissue rupture, maximum force, and energy required for yield and maximum force between groups. Energy to yield was 190.0, 167.8, and 188.95 N-mm for MI, Q, and MC closures, respectively. CONCLUSION: Biomechanical properties of staphylectomies closed with barbed or smooth sutures did not differ in this cadaveric model. CLINICAL SIGNIFICANCE: Barbed suture can be considered as an alternative for closure of canine staphylectomies. These results provide evidence to justify additional research to evaluate clinical outcomes in dogs undergoing staphylectomy.

Pharmacokinetics of a modified, compounded theophylline product in dogs.

Theophylline is a commonly used bronchodilator drug for treatment of chronic canine bronchitis, but no formulations validated in dogs are currently available. An oral, modified and compounded theophylline product (MCT), which could fulfil this need, is available through a USP-compliant, veterinary compounding pharmacy; however, its pharmacokinetic properties are unknown. The aim of this study was to determine the pharmacokinetics of MCT. Plasma drug concentrations were measured in seven healthy, fed dogs after single doses of intravenous aminophylline (8.6 mg/kg theophylline equivalent) and oral MCT (10 mg/kg). Systemic bioavailability of the MCT was 96.2 ± 32.9%. MCT times to maximum concentration, mean absorption time and terminal half-life were 8.85 ± 3.63, 6.95 ± 3.42, and 8.67 ± 1.62 hr, respectively. Based on simulations of 10 mg/kg and 12-hr dosing, steady-state plasma theophylline concentrations are expected to exceed the minimum therapeutic concentration for 71.7 ± 35.6% of the dosing interval. Overall, the MCT product investigated showed similar pharmacokinetic characteristics compared to previously validated extended-release theophylline products. An oral dose of 10 mg/kg q 12 hr is likely an appropriate dosage to begin therapy; however, therapeutic drug monitoring may be warranted because of inter-individual variation.

The association of physical examination abnormalities and carboxyhemoglobin concentrations in 21 dogs trapped in a kennel fire.

OBJECTIVE: To evaluate physical examination findings and their association with carboxyhemoglobin (COHb) concentrations in 21 dogs that were exposed to smoke during a kennel fire. SERIES SUMMARY: Twenty-one dogs were exposed to a kennel fire. Physical exam findings, presenting, and posttherapy COHb concentrations as well as therapeutic interventions were evaluated. COHb concentrations upon presentation were increased in all smoke inhalation exposed dogs. These dogs were compared to a small set of clinically normal staff-owned dogs who were not exposed to fire. Physical parameters significantly associated with higher COHb concentrations included lower body temperature, increased respiratory effort, abnormal respiratory auscultation, altered neurologic status, and length of hospital stay. Oxygen therapy resulted in a more rapid decline in COHb concentrations although 5 dogs still had mildly increased COHb concentrations 24-hour postadmission. UNIQUE INFORMATION PROVIDED: This study describes the relationship of admitting clinical findings of dogs exposed to a kennel fire with their initial blood COHb concentrations. It also describes the resolution of increased COHb concentrations with use of oxygen therapy and hospitalization. Additionally, COHb concentrations for a control group of dogs was evaluated and compared to the dogs exposed to smoke inhalation.

Nasal hydropulsion: a novel tumor biopsy technique.

Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for small animal practitioners. Multiple nasal biopsy techniques have been described in the past. This report describes a simplified flushing technique to biopsy and debulk nasal tumors, which often also results in immediate clinical relief for the patient. Based on the results of this retrospective study, the authors recommend high-pressure saline hydropulsion as a minimally invasive diagnostic, and potentially therapeutic, technique for nasal tumors in dogs and cats.

Nasopharyngeal turbinates in brachycephalic dogs and cats.

This retrospective study reports the presence and incidence of nasal turbinates in the nasopharynx (nasopharyngeal turbinates) in a population of brachycephalic dogs and cats exhibiting signs of upper respiratory disease. Medical records were reviewed for 53 brachycephalic dogs and 10 brachycephalic cats undergoing upper airway endoscopy. Nasopharyngeal turbinates were identified in 21% of brachycephalic animals, including 21% of dogs and 20% of cats. Pugs accounted for 32% of all dogs in the study population and 82% of dogs with nasopharyngeal turbinates. The presence of nasopharyngeal turbinates may play a role in upper airway obstruction in the brachycephalic airway syndrome.

Pharmacokinetics of an extended-release theophylline product in cats.

OBJECTIVE: To evaluate the pharmacokinetics of a brand of extended-release theophylline tablets and capsules in healthy cats. DESIGN: Randomized 3-way crossover study. ANIMALS: 6 healthy cats. PROCEDURES: A single dose of aminophylline (10 mg/kg [4.5 mg/lb], IV), a 100-mg extended-release theophylline tablet, or a 125-mg extended-release theophylline capsule was administered to all cats. Plasma samples were collected via preplaced central catheters throughout a 36-hour period. Plasma samples were frozen until analyzed by use of a fluorescence polarization monoclonal immunoassay. RESULTS: All cats tolerated drug administration and plasma collection with no adverse effects. Peak concentrations were reached for both orally administered products between 8 and 12 hours after administration. Bioavailability was excellent. Plasma concentrations were within the human therapeutic concentration of 5 to 20 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Daily administration of the brand of theophylline tablets and capsules used in this study at 15 mg/kg (6.8 mg/lb) and 19 mg/kg (8.6 mg/lb), respectively, maintained plasma concentrations within the desired therapeutic range in healthy cats.

Endoscopic bronchial anatomy in the cat.

The aim of this paper is to define the endoscopic bronchial anatomy of the cat and to adapt these findings to the bronchoscopic nomenclature previously described for the dog by Amis and McKiernan (Amis TC, McKiernan BC (1986) Systematic identification of endobronchial anatomy during bronchoscopy in the dog. American Journal of Veterinary Research 47(12), 2649-2657). In this study, the normal endoscopic bronchial anatomy was identified based on analysis of 10 air-dried feline lungs, two euthanased and eight healthy anesthetized cats using either a rigid or a flexible endoscope. Endoscopic photographs were taken during the examinations in the anesthetized cats for a photographic atlas. Corrosion casts were made from the 10 air-dried lungs to confirm the anatomy identified by bronchoscopy. With the results of our findings a bronchoscopic map of the feline bronchial tree and a photographic bronchoscopic atlas of the healthy cat were made.

Investigation of pulmonary deposition of a nebulized radiopharmaceutical agent in awake cats.

OBJECTIVE: To determine whether conscious, unsedated cats will inhale a nebulized material administered via a facemask and whether this material will reach the lower airways. ANIMALS: 20 healthy adult cats. PROCEDURE: Technetium Tc 99m-diaminetriaminopentaacetic acid (99mTc-DTPA) was nebulized into a spacer and administered to the cats via a closely fitting facemask. By use of a gamma camera, images were then immediately obtained to determine the distribution of 99mTc-DTPA within the lower airways. RESULTS: Images obtained by use of the gamma camera revealed that all 20 cats had inhaled 99mTc-DTPA from the facemask. In each cat, deposition of the radiopharmaceutical agent was evident throughout the lung fields. CONCLUSIONS AND CLINICAL RELEVANCE: Awake cats that were not used to the application of a facemask did inhale substances from such a device. Aerosolization of medications may be a feasible route of administration for cats with lower airway disease.

Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs.

OBJECTIVE: To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs. DESIGN: Randomized 3-way crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: A single dose of aminophylline (11 mg x kg(-1) 15 mg x lb(-1)], i.v., equivalent to 8.6 mg of theophylline/kg 13.9 mg x lb(-1) or extended-release theophylline tablets (mean dose, 15.5 mg x kg(-1) [7.04 mg x lb9-1), PO) or capsules (mean dose, 15.45 mg x kg(-1) [7.02 mg x lb(-1)], PO) was administered to all dogs. Blood samples were obtained at various times for 36 hours after dosing; plasma was separated and immediately frozen. Plasma samples were analyzed by use of fluorescence polarization immunoassay. RESULTS: Administration of theophylline i.v. best fit a 2-compartment model with rapid distribution followed by slow elimination. Administration of extended-release theophylline tablets and capsules best fit a 1-compartment model with an absorption phase. Mean values for plasma terminal half-life, volume of distribution, and systemic clearance were 8.4 hours, 0.546 L x kg(-1), and 0.780 mL x kg(-1) x min(1), respectively, after i.v. administration of theophylline. Systemic availability was > 80% for both oral formulations. Computer simulations predicted that extended-release theophylline tablets or capsules administered at a dosage of 10 mg x kg(-1) (4.5 mg x lb(-1)), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range of 10 to 20 microg x mL(-10. CONCLUSIONS AND CLINICAL RELEVANCE: Results of these single-dose studies indicated that administration of the specific brand of extended-release theophylline tablets or capsules used in this study at a dosage of 10 mg x kg(-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 microg x mL(-1)) in healthy dogs.

The effects of doxapram hydrochloride (dopram-V) on laryngeal function in healthy dogs.

Laryngeal dysfunction is assessed most accurately by direct visualization of the larynx under a light plane of anesthesia. If the plane of anesthesia used is too deep, laryngeal structures may appear paralyzed and remain in a paramedian position. Doxapram hydrochloride is a known respiratory stimulant. We hypothesized that doxapram would significantly increase intrinsic laryngeal motion in healthy anesthetized dogs. The goal of this study was to evaluate the effect of doxapram on the area of rima glottidis (RG) in healthy dogs. Thirty healthy dogs were studied. Dogs were premedicated with butorphanol tartrate (0.22 mg/kg IV), acepromazine maleate (0.05 mg/kg SC), and glycopyrrolate (0.005 mg/kg SC), followed by induction with propofol (4 mg/kg IV). Intrinsic laryngeal motion observed in each dog was recorded on videotape after induction. Doxapram then was administered (2.2 mg/kg IV) and respirations again were recorded. Representative breaths for each dog were photographed during 4 phases of respiration (inspiration at rest, inspiration with doxapram, expiration at rest, and expiration with doxapram). The area of the RG then was calculated by using a computer-assisted analysis program. Results of each category were compared by using a 1-way analysis of variance; P < or = .05 was considered significant. Doxapram visibly increased respiratory effort, and was associated with increased intrinsic laryngeal motion. Compared to the resting state, the area of the RG was significantly increased after doxapram administration during both inspiration and expiration. We propose the routine use of doxapram during laryngoscopy to increase intrinsic laryngeal motion and aid in the diagnosis of laryngeal dysfunction.