EVALUATION OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN NORMAL CATS

The non-ionic, iodinated contrast medium, iohexol (240 mg I/ml) was evaluated as a gastrointestinal (GI) contrast medium in cats. Iohexol, both undiluted and diluted with tap water, was administered via a percutaneous endoscopically-placed gastrotomy (PEG) tube to 4 mature clinically normal cats. The dilution of contrast medium administered was 1:1, 1:2, and 1:3, and doses were 10 ml/kg and 5 ml/kg body weight. All combinations of dilution and dose of iohexol provided adequate visualization of the contrast medium column within the GI tract, and results were not significantly different than those observed using 30% w/v barium sulfate. Dehydration and diarrhea were not observed after contrast medium administration, but vomiting occurred within 15–30 minutes after administration of undiluted iohexol in all experimental cats. Renal opacification did not occur on exposures made through a 2 hour period, and dilution in transit was not apparent.     

USE OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN THE DOG

Iohexol was administered orally in five dogs. The dose, gastrointestinal (GI) transit time, appearance of mucosal patterns and side effects were studied. Three different doses (525, 700, 875 mgI/kg) were used in each dog at 1-week intervals. GI transit time was rapid. In each dose, gastric emptying commenced immediately after administration of the contrast medium, and was completed within 30–60 min with doses of 525–700 mgI/kg and 90–120 min with 875 mgI/kg. Large intestinal filling was observed within 60-90 min. In the majority of studies, the mucosal border appeared as a thin homogeneous halo of lucency surrounding the more opaque bowel lumen contents. The contrast intensity was not adequate with the lowest dose. The image quality did not deteriorate along the GI tract. No adverse reactions were found. Iohexol is an alternative GI contrast medium in the dog when contrast media are contraindicated.     

IOHEXOL MYELOGRAPHY IN THE DOG

Myelography with iohexol (180 mg iodine/ml, 0.25 ml/kg), a new nonionic radiologic contrast medium, was performed in 100 dogs of 33 different breeds. In 96 of the dogs the iohexol mixed evenly with the cerebrospinal fluid, providing an homogeneous, continuous column of contrast medium within the subarachnoid space, and a radiologic diagnosis of a normal myelogram or disease involving the spinal cord was made. Pooling of iohexol in the dorsal part of the subarachnoid space occurred in four dogs; whether this was related to poor mixing of contrast medium with cerebrospinal fluid or disease of the spinal cord and meninges requires further study. Postmyelographic signs of central nervous system irritation (fasciculations of the temporal muscles and three episodes of seizure activity) were observed in only one dog and were controlled with diazepam. The presenting neurologic signs were aggravated after myelography in four other dogs, two of which were eventually killed. This study provided further evidence of the increased safety of iohexol compared with metrizamide, the first of the nonionic media, as a contrast medium for myelography in the dog.     

Comparison of different doses of iohexol with amidotrizoate for excretory urography in cats.

In five cats with normal renal function, doses of 200, 400, 600 and 800 mg iodine kg(-1)bodyweight of iohexol (350 mg iodine ml(-1)) were assessed in comparison to a dose of 880 mg iodine kg(-1)bodyweight of meglumine-sodium amidotrizoate (370 mg iodine ml(-1)) to determine the smallest dose which produces diagnostically adequate results for excretory urography. Urographic quality, haematologic and biochemical parameters, urinalysis and urinary osmolality, pulse and respiratory rates, blood pressure and adverse effects were determined. Iohexol presented fewer adverse reactions and influenced blood pressure less than amidotrizoate. The smallest dose of iohexol which provided urograms of similar quality to amidotrizoate was 400 mg iodine kg(-1)bodyweight. This study suggests that iohexol is safer and produces urograms of better quality than amidotrizoate.     

Gastrografin as a Gastrointestinal Contrast Medium in the Cat

Gastrografin (diatrizoate meglumine and diatrizoate sodium solution) was used to evaluate its performance as a gastrointestinal-tract contrast medium in ten cats. It was administered through an orogastric tube to ketamine hydrochloridesedated, nonatropinized, mature cats at a dose rate of 22 mg/kg. Gastric emptying and largeintestinal filling were observed within 30–60 minutes in seven cats and in 120 minutes in the remaining three cats. The mucosal detail of the small intestine was poor, being represented by a homogeneous "halo" of decreased radiodensity surrounding the more radiodense intestinal luminal contents. The contrast medium refluxed into the esophagus in six cats. Some contrast medium precipitated in the stomach and small intestines in all ten cats. Urinary-tract opacification occurred in all cats and was first seen 60 minutes after Gastrografin was administered. Gastrografin satisfactorily opacifies the lumen of the gastrointestinal tract of cats. It has physical and physiologic characteristics that preclude its use for routine gastrointestinal contrast studies. These characteristics are reviewed in this article.     

Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats

OBJECTIVE: To determine whether plasma clearance of iohexol (PCio) can be used to estimate glomerular filtration rate (GFR) in cats. ANIMALS: 4 renal-intact and 6 partially nephrectomized adult cats. PROCEDURE: Plasma clearance of iohexol was determined after IV administration of iohexol; plasma concentrations of iodine were measured by use of a colorimetric assay. Results for PCio were compared with simultaneously obtained values for urinary clearance of creatinine (CCr). RESULTS: The colorimetric assay used to measure plasma iodine concentrations was extremely precise. Results of PCio for all cats, renal-intact cats, and partially nephrectomized cats were closely associated with results of CCr. Mean difference between CCr and PCio determined for all cats was 0.95 ml/min/kg, which was < 30% of mean CCr for renal-intact cats. Coefficients of variance for PCio (5%) and CCr (8%) in renal-intact cats were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearance of iohexol determined by use of a simple colorimetric assay provided an estimation of GFR in cats that was not significantly different from that provided by CCr. Moreover, PCio more reliably estimates renal function than BUN and plasma creatinine concentrations. Because determination of PCio is less labor intensive and invasive, compared with CCr, it may be easier to perform in a clinical setting.     

NON-SELECTIVE ANGIOCARDIOGRAPHY IN THE NORMAL DOG AND CAT

Non-selective angiocardiograms were performed on clinically normal mature dogs and cats to determine the optimal contrast medium dose. A dose of 200 mg of iodine per 0.45 kg of body weight was found to give the most consistent results. A 105 mm spot film camera was used at a speed of 2 frames per second. No study took longer than 11 seconds to complete. The technique provided good visualization of the cranial vena cava, pulmonary outflow tract, the pulmonary arteries, left atrium, left ventricle and aorta. The technique provided fair visualization of the right atrium, right ventricle, valves and papillary muscles     

Radiographic assessment of laryngeal reflexes in ketamine-anesthetized cats

The competence of the laryngeal closure reflexes of cats anesthetized with ketamine was assessed. Radiographic evaluations of the respiratory and digestive tracts were made after colloidal barium suspension was instilled into the pharynges of conscious and ketamine-anesthetized cats. There was a significant ketamine dose-related response of spread of contrast medium into the supraglottic laryngeal area and into the stomach 2 minutes after contrast medium was instilled into the pharynx (P less than 0.05). Cats did not aspirate contrast medium into the lower respiratory tract. Three ketamine-anesthetized cats aspirated contrast medium into the subglottic area of the larynx, and 2 of these cats also aspirated the material into the cranial part of the trachea. This material was coughed up and swallowed within 5 minutes. Transit time of contrast medium into the stomach seemed to be increased in 11 of the 15 cats given the larger dosages of ketamine (24, 36, 48 mg/kg of body weight), compared with that in conscious cats and those given ketamine at 12 mg/kg. Competent laryngeal protective reflexes in cats can be maintained with ketamine anesthesia. Contrast radiography could be used as a diagnostic aid in ketamine-anesthetized cats suspected of laryngeal reflex abnormalities.     

Effect of contrast media formulation on computed tomography angiographic contrast enhancement.

The characteristics of contrast media formulation (mgI/ml, osmolarity, and viscosity) are generally not considered important in computed tomography (CT) angiography in animals. The purpose of this study was to assess the contrast effect in CT angiography as a function of contrast media formulation, with a constant iodine dose. The contrast effects of three contrast media with different iodine concentrations were compared by administering identical iodine dosages (mgI/kg). The contrast effects of the three contrast media differed, and the area under the time-attenuation curve of iohexol 350 mgI/ml, which had the highest iodine concentration, was the lowest. It was hypothesized that the contrast effect of a contrast medium decreases with higher iodine concentration because of the high amount of residual iodine present in the circulatory system from the injection site to the portion immediately before the great vessels. In addition, the influence of osmotic dilution on contrast media with high osmolarity was also considered. In conclusion, the contrast effect varies with different contrast media formulations, even when the same iodine dosage is administered.     

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats

The present study characterizes the safety, pharmacokinetics, and anti-emetic effects of the selective NK-1 receptor antagonist maropitant in the cat. Safety of maropitant was determined following 15 days of subcutaneous (SC) administration at 0.5–5 mg/kg. Maropitant was well tolerated in cats at doses that exceeded the efficacious anti-emetic dose range of the drug by at least a factor of 10 and adverse clinical signs or pathological safety findings were not noted at any dose.The pharmacokinetics of maropitant in cats were determined following single dose oral (PO), intravenous (IV) and SC administration. Maropitant had a terminal half-life of 13–17 h and a bioavailability of 50 and 117% when administered PO and SC, respectively. Efficacy was determined against emesis induced either by xylazine or by motion. A dosage of 1 mg/kg maropitant administered IV, SC or PO prevented emesis elicited by xylazine. The compound had good oral antiemetic activity and a long (24 h) duration of action. Maropitant (1.0 mg/kg) was highly effective in preventing motion-induced emesis in cats. These studies indicate that the NK-1 receptor antagonist maropitant is well tolerated, safe and has excellent anti-emetic properties in cats.     

Disposition of plasma creatinine in non-azotaemic and moderately azotaemic cats

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3+/-0.66 ml/min/kg) was significantly higher (P<0.001) than that of exo-iohexol (1.7+/-0.40 ml/min/kg). The volume of distribution (447+/-97 ml/kg) and elimination half-life (181+/-77 min) of creatinine were also higher (P<0.001) than those of exo- and endo-iohexol. The estimated daily endogenous production of creatinine was 65+/-23 mg/kg. None of the pharmacokinetic parameters was changed by the azotaemic status of the animals.     

Normal canine excretory urogram: effects of dose, time, and individual dog variation

Ten healthy, young, adult mongrel dogs were given sodium iothalamate at dose levels of 200, 400, and 800 mg of iodine/0.45 kg of body weight on separate occasions by rapid IV injection; urinary bladders of the dogs were empty before injections were begun. Seven of the ten dogs were given an additional dose of sodium iothalamate (400 mg of iodine/0.45 kg) with the bladder partially distended with sterilized saline solution. Ventrodorsal abdominal radiographs were obtained immediately and at 5, 10, 20, 40, 60, and 120 minutes after injection of contrast medium. The kidneys, renal pelves, pelvic diverticula, and ureters were evaluated for radiographic density (radiopacity). The lengths and widths of the kidneys, pelves, and diverticula and the width of the ureters were determined, and those measurements were standardized by dividing the values by the corresponding length of the second lumbar vertebral body. From these evaluations, it was determined that postinjection radiographs should be obtained immediately and at 5, 20, and 40 minutes. The optimal dose of contrast medium was 400 mg of iodine/0.45 kg of body weight. It was also determined that the dose of contrast medium, as well as the time of postinjection radiography, significantly influenced many of the measurements (both linear and density) in the excretory urogram of normal dogs. Values for the measurements of the urinary structures based on the results of the present study are also presented.     

Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with Carcinomas

Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas.
Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats.
Animals: Twenty cats with spontaneously occurring carcinomas.
Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days.
Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1–6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5–10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs).
Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored.     

CT thoracic duct lymphography in cats by popliteal lymph node iohexol injection

Three different doses (1.0, 1.5, and 2.0 ml) of iohexol (300 mgl/ml) were injected percutaneously into the popliteal lymph node of eight adult cats under ultrasound guidance. Serial transverse CT images of five regions of interest (L3, T13, T8, T4, and T1 level) were performed at 2-min intervals, and the attenuation in Hounsfield Units (HU) of the lymphatic vessels was measured for determination of the optimal dose of iohexol and CT scan parameters. The optimal dose was 1.5 ml and helical CT acquisition is recommended to be performed as soon as possible after iohexol injection. In helical scans, the thoracic duct was characterized by variable branch numbers that formed a single trunk and entered the venous system at variable levels. CT lymphography using this protocol was performed in a cat with chylothorax. The thoracic duct was tortuous and focally dilated, and leakage of contrast medium was observed. Percutaneous CT lymphography using ultrasound-guided administration of iohexol into the popliteal lymph node appears reliable for delineation of the thoracic duct in cats.     

Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat

Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT(4)) and for the thyroid to salivary gland ratio with sodium pertechnetate gamma-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT(4) and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.     

Pharmacokinetics and pharmacodynamics of ramipril and ramiprilat in healthy cats

The pharmacokinetics of ramipril and its active metabolite, ramiprilat, was determined in cats following single and repeated oral doses of ramipril (Vasotop^® tablets) (once daily for 9 days) at dose rates of 0.125, 0.25, 0.5 and 1.0 mg/kg. The pharmacodynamic effects were assessed by measuring plasma angiotensin-converting enzyme (ACE) activity. Maximum ramipril concentrations were attained within 30 min following a single dose and declined rapidly (concentrations were below the limit of quantification 4 h after treatment). Peak ramiprilat concentrations were detected at approximately 1.5 h. The apparent terminal half-life ( t _{½ β} ) was ≥20 h irrespective of the dose. Ramiprilat accumulated in plasma (ratio of accumulation 1.3 to 1.9 depending on the dose rate) following repeated administration. Steady-state conditions were attained after the second dose. Excretion was predominant in faeces (87%) and to a lesser extent in urine (11%). The rate and extent of absorption of ramipril as well as its conversion to ramiprilat were not significantly influenced by the presence of food in the gastrointestinal tract. Plasma-ACE activity was almost completely abolished 0.5–2.0 h after treatment, irrespective of the dose rate. Significant inhibition of ACE activity of 54.7 to 82.6% (depending on the dosage) was still present 24 h after treatment. Treatment was well-tolerated in all cats. Ramipril at a dose rate of 0.125 mg/kg once daily produces significant and long-lasting inhibition of ACE activity in healthy cats. The appropriateness of this dosage regime needs to be confirmed in diseased cats.     

Pharmacokinetics of tinidazole in dogs and cats

Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study. Tinidazole was completely absorbed at both oral dose levels in cats and dogs. Peak tinidazole concentration in plasma was 17.8 micrograms/ml in dogs and 22.5 micrograms/ml in cats after 15 mg/kg p.o. The oral dose of 30 mg/kg resulted in peak levels of 37.9 micrograms/ml in dogs and 33.6 micrograms/ml in cats. The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half-life that was twice as long in cats (8.4 h) as in dogs (4.4 h). The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats. Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole-sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg. From the pharmacokinetic standpoint tinidazole seems to be well-suited to clinical use in small animal practice.     

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.     

Drug residues in food animals II. Plasma and tissue kinetics of oxytetracycline in young cross-bred swine

Tissue distribution and elimination kinetics of oxytetracycline in sixteen organs and body fluids were determined in young pigs following intravenous and oral administration. Seventeen non-fasted pigs, 8–10 weeks of age, weight range 16.4–34.5 kg were dosed intravenously at a dose rate of 11 mg/kg bodyweight. An additional seventeen weaning pigs, 12–14 weeks of age, weight range 27.2–36.3 kg were dosed orally at a dose rate of 48–65 mg/kg bodyweight. Oxytetracycline was rapidly distributed (half-life, 6.71 ± 1.13 min) in swine. The mean volume of distribution was 1.26 ± 0.18 l/kg and overall body clearance was 3.82 ± 0.59 ml/kg/min. The elimination half-life of oxytetracycline in pigs was 3.87 ± 0.62 h, which is shorter than has been observed in other domestic animal species. Oxytetracycline became rapidly and efficiently involved in enterohepatic cycling, with as much as 70% of a total intravenous dose being available for reabsorption from the gastrointestinal tract within 1 h after administration. This high degree of enterohepatic recycling prolonged the half-life, and the large amount of drug that entered the enteric tract contributed to the high volumes of distribution and high k ₁₂/ k ₂₁ ratios. The excellent tissue penetration of this drug further contributed to the high volume of distribution and high k ₁₂/ k ₂₁ ratios obtained. Relationships between plasma and tissue depletion for several major edible organs were found to be statistically significant. Blood plasma is proposed as a body fluid for monitoring oxytetracycline tissue residues.     

THE EFFECTS OF IOHEXOL ADMINISTRATION ON TECHNETIUM THYROID SCINTIGRAPHY IN NORMAL CATS

Administration of iodinated contrast medium interferes with iodide uptake in the human thyroid gland and compromises diagnostic thyroid scintigraphy and radioiodine treatment for 4–6 weeks. However, the degree and duration of inhibition of thyroid uptake of pertechnetate (^99mTcO₄^?) by iodinated contrast medium has not been established in any species. The main objective of this study was to better understand the temporal characteristics and magnitude of inhibition of feline thyroid uptake of ^99mTcO₄^? due to iohexol administration. Routine thyroid scintigraphy was performed in eight cats by intravenous (IV) injection of 185 MBq (5 mCi) of ^99mTcO₄^? both 4 days before and 0,1, 3, 7,14, and 28 days after IV administration of 880 mg I/kg iohexol (240 mg I/ml). Thyroid scintigraphy data were used to calculate thyroid:salivary gland ratios (T:S) and the percentage of total injected ^99mTcO₄^? dose uptake within the thyroid (%TU) at 20 min postinjection. After iohexol administration, mean T:S was significantly decreased below baseline only on day 1. At no point during the study did any cat have a T:S that fell below the published normal reference range of 0.71±0.14. There was a significant decrease in %TU on day 1, 3, and 14; however, at no point during the study, did any cat have a %TU that fell below the published normal reference ranges of 0.64±0.57, 0.68±0.9, or 0.75±1.38.