Objective-To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons ( Python regius ) after IV or oral administration of a single dose. Animals-2 male and 5 female ball pythons. Procedures-Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry. Results-After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 micrograms/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration. Conclusions and Clinical Relevance-Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.

Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (+/- the standard error of the mean) was 1.32 +/- 0.09 h−l, the mean elimination half-life was 0.53 +/- 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 +/- 98 μg · min/mL, the plasma clearance was 472 +/- 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 +/- 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 +/- 0.80 μg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 +/- 5.46 μg/mL at 2 h, then decreased to 1.92 +/- 0.25 μg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 +/- 94.55 μg · min/mL and the bioavailability was 0.17 +/- 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 +/- 0.10 μg/mL at 0.67 h, then declined to 0.37 +/- 0.37 μg/mL by 36 h; the plasma concentration of SA peaked at 23.90 +/- 4.94 μg/mL at 4 h and decreased to 0.85 +/- 0.31 μg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 +/- 24.90 μg · min/mL and the bioavailability was 0.059 +/- 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate.

Six tests for the detection of West Nile virus (WNV) antibodies in the serum of experimentally infected chickens were compared. The tests included the hemagglutination-inhibition test (HIT), immunoglobulin M (IgM)-capture enzyme-linked immunosorbent assay (ELISA) with WNV-infected mouse brain antigen, immunoglobulin G (IgG) indirect ELISA with tickborne encephalitis viral antigen, the microtitre virus neutralization test, the standard plaque reduction neutralization test (PRNT), and the microtitre PRNT (micro-PRNT). Thirty adult chickens, intravenously and intramuscularly inoculated with 107 plaque-forming units (PFU) of WNV strain Egypt 101, were bled and given a booster of 107 PFU at 7, 15, and 21 d postinoculation; the final blood collection was on day 28. Although the micro-PRNT is capable of detecting the highest antibody titres during both early and late infection, because of the technical complexity and time requirements of this test a combination of IgM and IgG ELISAs is recommended for serologic screening. Serum samples that give positive results in the ELISAs can then be tested by the micro-PRNT to determine the specificity of antibodies to WNV.

Objective-To determine whether pharmacokinetic analysis of data derived from a single IV dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. Animals-10 healthy foals. Procedure-Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. Results-Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. Conclusions and Clinical Relevance-Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after IV injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.

Objective-To evaluate response of euthyroid cats to administration of recombinant human thyroid-stimulating hormone (rhTSH). Animals-7 healthy cats. Procedure-Each cat received each of 5 doses of rhTSH (0, 0.025, 0.050, 0.100, and 0.200 mg), IV, at 1-week intervals. Serum concentration of total thyroxine (TT4) and free thyroxine (fT4) was measured immediately before each injection (time 0) and 2, 4, 6, and 8 hours after administration of each dose. Results-Overall TT4 response did not differ significantly among cats when administered doses were ≥ 0.025 mg. Serum TT4 concentrations peaked 6 to 8 hours after administration for all doses greater than 0.025 mg. For all doses greater than 0.025 mg, mean +/- SEM TT4 concentration at 0, 6, and 8 hours was 33.9 +/- 1.7, 101.8 +/- 5.9, and 101.5 +/- 5.7 nmol/L, respectively. For all doses greater than 0.025 mg, mean fT4 concentration at 0, 6, and 8 hours was 38.7 +/- 2.9, 104.5 +/- 7.6, and 100.4 +/- 8.0 pmol/L, respectively. At 8 hours, the fT4 response to 0.025 and 0.050 mg was less than the response to 0.100 and 0.200 mg. Adverse reactions after rhTSH administration were not detected. Conclusions and Clinical Relevance-The TSH stimulation test can be performed in cats by IV administration of 0.025 to 0.200 mg of rhTSH and measurement of serum TT4 concentrations at time of injection and 6 or 8 hours later. Clinical validation of the TSH stimulation test would facilitate development of additional tests of thyroid gland function, such as a TSH assay.

Objective-To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-alpha (TNF-alpha) activity in healthy dogs. Animals-6 healthy adult male dogs. Procedures-Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-alpha activity were measured before (day-1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours. Results-Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-alpha activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity. Conclusions and Clinical Relevance-Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 and T3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs.

The objective of this study was to describe the kinetics of urinary recovery and to evaluate the effects of postmucosal factors on urinary recovery of 5 intravenously administered saccharides. Ten cats received an isotonic sugar solution containing lactulose, rhamnose, xylose, methylglucose, and sucrose intravenously. These sugars were selected because of their prior use for intestinal permeability and mucosal function testing in humans and dogs. Urethral catheterization with a closed collection system was used for collection of cumulative urine samples prior to and 2, 4, 6, 8, 10, 12, and 24 h after administration of the sugar solution. High-pressure anion exchange liquid chromatography with pulsed amperometric detection was used to measure the concentrations of each sugar in the urine and calculate urinary recovery. Twenty-four hour cumulative urinary recovery for each sugar from the cats, was lower than expected compared to dogs and humans. All 5 sugars had the highest percentage of urinary recovery during the first 2 h after administration. Mean sugar elimination rate constants and half-lives ranged from 0.268/h for methylglucose to 0.415/h for lactulose and 1.67 h for lactulose to 2.59 h for methylglucose, respectively. Metabolism and incomplete urine collection are possible reasons for lower cumulative urinary recoveries of these 5 sugars in cats compared with dogs. Although these 5 sugars are not ideal marker molecules, they may still be useful for intestinal permeability and mucosal function testing in cats.

Objective-To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO. Animals-6 adult horses. Procedure-Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). Arterial blood samples were obtained before and after MOR and analyzed. Results-Mean +/- SD baseline ISO MAC was 1.43 +/- 0.06%. The ISO MAC did not change with time after administration of saline solution. Effects of MOR on ISO MAC varied. Maximal change in MAC ranged from –20.2 to +28.3% and -18.9 to +56.2% after low and high doses of MOR, respectively. Typical half-life of MOR in plasma was 40 to 60 minutes and related to dose. Mean PaCO2 increased from 70 mm Hg before MOR to 88 to 102 mm Hg for 30 to 240 minutes after the high dose of MOR. Recovery from anesthesia after administration of the high dose of MOR was considered undesirable and dangerous. Conclusions and Clinical Relevance-Our results do not support routine clinical use of MOR administered IV at dosages of 0.25 or 2.0 mg/kg as an adjuvant to anesthesia in horses administered ISO.

Objective-To characterize insulin-sensitive glucose-transporter (GLUT-4) protein in equine tissues and determine effects of exercise and glucose administration on content of GLUT-4 protein in equine skeletal muscle. Sample Population-Tissue samples from 9 horses. Procedure-Western blot analyses were performed on crude membrane preparations of equine tissues to characterize GLUT-4. In a crossover, randomized study, horses were strenuously exercised for 3 consecutive days and then administered 13.5% glucose or isotonic saline (0.9% NaCl; control) solution, IV, at similar infusion rates for 12.1 hours. Samples were collected from the middle gluteal muscle before and after exercise and 10.1 hours after completion of an infusion and used for measurements of glycogen concentration and total content of GLUT-4 protein. Results-Immunoblot analyses detected specifically immunoreactive bands for GLUT-4 in insulin-sensitive tissues. Content of GLUT-4 protein in skeletal muscle increased significantly by 27.3 and 12.3% 22.2 hours after exercise for control and glucose groups, respectively. Intravenous infusion of glucose resulted in a significantly higher rate of glycogenesis, compared with results for the control group (mean +/- SD, 3.98 +/- 0.61 and 1.47 +/- 0.20 mmol/kg/h, respectively). Despite enhanced glycogenesis, we did not detect an increase in content of GLUT-4 protein after glucose infusion, compared with values after exercise. Conclusions and Clinical Relevance-GLUT-4 protein was expressed in equine skeletal and cardiac muscles. Exercise increased total content of GLUT-4 protein in skeletal muscle, and replenishment of muscle glycogen stores after glucose infusion attenuated the exercise-induced increase in the content of GLUT-4 protein in equine skeletal muscle.

The purpose of this study was to collect initial data to determine the potential clinical usefulness of a 13C-aminopyrine demethylation blood test, and whether additional clinical investigation is warranted. Six dogs, initially suspected of having hepatic disease based on their history, physical examination, imaging studies, general laboratory parameters, or any combination of the above, were enrolled in the study. A baseline blood sample was collected, 2 mg/kg 13C-aminopyrine was administered intravenously, and another blood sample was collected 45 min afterwards. Carbon dioxide was extracted from the blood samples and analyzed using fractional mass spectrometry. Results from the 13C-aminopyrine demethylation blood test were compared to clinical data and histologic findings. Intravenous administration of 13C-aminopyrine leads to a decrease in the percent dose of 13C recovered from dogs with histologically confirmed liver disease. Based on our results, a full-scale investigation of the potential clinical usefulness of a 13C-aminopyrine demethylation blood test for assessment of hepatic function in dogs is warranted.