Associations between meal size, gastric emptying and post-prandial plasma glucose, insulin and lactate concentrations in meal-fed cats.

Plasma glucose and insulin concentrations are increased for 12-24 h in healthy cats following moderate- to high-carbohydrate meals. This study investigated associations between gastric emptying time and post-prandial plasma glucose, insulin and lactate concentrations in cats fed an extruded dry, high-carbohydrate, moderate-fat, low-protein diet (51, 28, 21% metabolizable energy, respectively) once daily by varying meal volume. Eleven healthy, non-obese, neutered adult cats were enrolled in a prospective study and fed to maintain body weight. Ultrasound examinations were performed for up to 26 h, and blood collections over 24 h after eating meals containing approximately 100% and 50% of the cats' daily caloric intake (209 and 105 kJ/kg BW, respectively). Gastric emptying time was increased after a meal of 209 kJ/kg BW compared with 105 kJ/kg BW (median gastric emptying times 24 and 14 h, respectively; p = 0.03). Time for glucose to return to fasting was longer after the 209 kJ/kg BW meal (median 20 h; 25th and 75th percentiles 15 and 23 h, respectively) than the 105 kJ/kg BW meal (13, 12 and 14 h; p < 0.01); however, peak glucose was not higher after the 209 kJ/kg BW meal compared with the 105 kJ/kg BW meal [(mean ± SD) 6.6 ± 0.6 and 7.8 ± 1.2 mmol/l, respectively, p = 0.07]. Times for insulin to return to fasting were not significantly longer after the 209 kJ/kg BW meal than the 105 kJ/kg BW meal (p = 0.29). d- and l-lactate concentrations were not associated with gastric emptying time or post-prandial blood glucose and insulin. Based on results obtained, prolonged gastric emptying contributes to prolonged post-prandial hyperglycemia in cats meal fed a high-carbohydrate, low-protein, dry diet and fasting times for cats' meal-fed diets of similar composition should be 14-26 h, depending on meal size.

[Pathologic-anatomic and morphometric examinations on the heart in feral cockatoos]. / Pathologisch-anatomische und morphometrische Untersuchungen am Herzen von wildlebenden Kakadus.

OBJECTIVE: To evaluate the heart of free-living psittacine birds macroscopically and morphologically, and to compare the results to findings published for psittacine birds living in captivity to obtain information on the influence of bird keeping in a human environment on the psittacine heart. MATERIAL AND METHODS: In total, 84 wild-living cockatoos were examined, including 50 sulphur-crested cockatoos (Cacatua galerita), 31 galahs (Eolophus roseicapilla) and three long-billed corellas (Cacatua tenuirostris). The birds were euthanized because of a local cockatoo control program in Australia, and were examined pathologically within 8 hours of euthanasia. A macroscopic necropsy was performed, and the heart was assessed morphologically. Furthermore, a histological organ screening was conducted. RESULTS: The birds demonstrated good body condition and excellent muscle condition. Except for some paleness of the heart muscle, none of the animals showed any pathological alteration of the heart or large vessels. The mean heart mass was 8.7 g for the sulphur-crested cockatoos, 5.3 g for the galahs and 8.6 g for the long-billed corellas. Independent of the species examined, a highly significant correlation was found between the heart and body masses (r = 0.91; p < 0.001), which was also confirmed as significant within the sulphur-crested cockatoo (r = 0.59; p < 0.001) and galah groups (r = 0.52; p = 0.003). This correlation can be used to calculate the expected heart mass based on the body mass, using the formula: heart mass (g) = 2.9 + 0.01 x body mass (g). In comparison to reports on Australian parakeets, the relative thickness of the heart muscle wall of the left ventricle found in this study was greater. CONCLUSION: In comparison to psittacine birds kept in captivity, wild-living cockatoos have good body condition and rarely suffer from macroscopically detectable diseases of the heart or large vessels. The cardiac fitness level is superior in comparison to that found in healthy appearing psittacine birds kept in captivity. CLINICAL RELEVANCE: The results can serve as a basis for the assessment of the heart in psittacine birds, because in contrast to earlier reports, the heart of healthy psittacine birds not previously exposed to any human influence could be assessed.

Risk factors for multidrug-resistant Escherichia coli rectal colonization of dogs on admission to a veterinary hospital.

This study aimed to identify risk factors for intestinal colonization with multidrug-resistant (MDR) E. coli in dogs on admission to a veterinary teaching hospital. Exposures to potential risk factors, including prior treatments, hospitalizations and interventions during the 42 days prior to admission were assessed for 82 case admissions and 82 time-matched controls in a retrospective prevalence-based case-control study of 20 months duration. On multivariable analyses, risk of MDR E. coli colonization on admission was increased with prior hospitalization for 4-7 days and >7 days relative to shorter periods, and in dogs that had prior diagnostic imaging techniques. Univariable analyses indicated that risk was increased following prior treatment with several antimicrobial agents. However, on multivariable analysis, administration of fluoroquinolones was associated with increased risk but risk did not appear to increase following administration of other antimicrobials. These results can inform management of canine patients and infection control procedures to mitigate the risk of clinical disease due to MDR bacteria in hospitalized dogs.

Risk factors for dogs becoming rectal carriers of multidrug-resistant Escherichia coli during hospitalization.

This study aimed to identify risk factors for dogs becoming rectal carriers of multidrug-resistant (MDR) Escherichia coli while hospitalized in a veterinary teaching hospital. Exposures to potential risk factors, including treatments, hospitalization, and interventions during a 42-day pre-admission period and hospitalization variables, were assessed for 90 cases and 93 controls in a retrospective, risk-based, case-control study. On multivariable analyses, hospitalization for >6 days [odds ratio (OR) 2·91-8·00], treatment with cephalosporins prior to admission (OR 5·04, 95% CI 1·25-20·27), treatment with cephalosporins for >1 day (OR 5·18, 95% CI 1·86-14·41), and treatment with metronidazole (OR 7·17, 95% CI 1·01-50·79) while hospitalized were associated with increased risk of rectal carriage of MDR E. coli during hospitalization. The majority of rectal isolates obtained during the study period conformed to MDR E. coli clonal groups previously obtained from extraintestinal infections. These results can assist the development of improved infection control guidelines for the management of dogs in veterinary hospitals to prevent the occurrence of nosocomial clinical infections.

Using a GnRH agonist to obtain an index of testosterone secretory capacity in the cockatiel (Nymphicus hollandicus) and sulphur-crested cockatoo (Cacatua galerita).

OBJECTIVE: Validation of a stimulation test for determining the steroidogenic capacity of the parrot testis. The major aim was to characterise testosterone secretion after injection of a gonadotropin-releasing hormone agonist (GnRHa), then use the test to investigate seasonal reproduction in the male cockatiel. PROCEDURE: A synthetic GnRHa (buserelin; 8.0 microg of peptide/kg bodyweight) was injected IM into male cockatiels (n = 7) and sulphur-crested cockatoos (n = 3) and serial blood samples collected at 0, 30, 60, 90 and 120 min after administration. Once validated, the technique was subsequently used to examine seasonal changes (23 months) in the testosterone profile of a captive cockatiel population. RESULTS: Injection of buserelin resulted in a significant increase in the testosterone concentration of cockatiel plasma, with maximal concentrations occurring at approximately 60 (1.33 +/- 0.08 ng/mL) to 90 min (1.22 +/- 0.08 ng/mL) after injection. Although no clear pattern of seasonal variation in testosterone secretion was detected in cockatiel plasma, samples taken 60 and 90 min after administration showed a significant increase in all seasons. Injection of buserelin in the sulphur-crested cockatoo also resulted in increased testosterone secretion, with maximal concentrations obtained after 90 min. CONCLUSION: Buserelin can be used to obtain a reliable index of the prevailing testosterone capacity of the cockatiel and cockatoo testis. With further studies, this test may be incorporated into clinical assessment of reproductive status.

Multidrug-resistant E. coli and enterobacter extraintestinal infection in 37 dogs.

BACKGROUND: Extraintestinal infections caused by multidrug-resistant (MDR) Escherichia coli and Enterobacter are becoming more common in veterinary medicine. OBJECTIVE: To generate hypotheses for risk factors for dogs acquiring extraintestinal infection caused by MDR E. coli and Enterobacter, describe antimicrobial resistance profiles and analyze treatment and clinical outcomes. ANIMALS: Thirty-seven dogs diagnosed with extraintestinal infection caused by MDR E. coli and Enterobacter spp. between October 1999 and June 2006. METHODS: Retrospective case series assembled from hospital records data, including clinical history before 1st MDR isolation and treatment outcome. Identity and antimicrobial susceptibility profiles were confirmed by standard microbiological techniques for 57 isolates. RESULTS: Most dogs had an underlying disease condition (97%), received prior antimicrobial treatment (87%), were hospitalized for >or =3 days (82%), and had a surgical intervention (57%). The urinary tract was the most common infection site (62%), and urinary catheterization, bladder stasis, or both were common among dogs (24%). Some dogs were treated with high doses of co-amoxyclavulanate (n = 14) and subsequently recovered even though the isolates showed in vitro resistance to this antimicrobial. Other dogs were successfully treated with chloramphenicol (n = 11) and imipenem (n = 2). CONCLUSION AND CLINICAL IMPORTANCE: Predisposing disease condition, any prior antimicrobial use rather than a specific class of antimicrobial, duration of hospitalization, and type of surgical procedure might be risk factors for acquiring MDR extraintestinal infections. Whereas culture and sensitivity results can indicate use of last-resort antimicrobials such as imipenem for MDR infections, some affected dogs can recover after administration of high doses of co-amoxyclavulanate.

Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur-crested cockatoos (Cacatua galerita).

The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma doxorubicinol concentrations were measured by HPLC. The pharmacokinetic parameters were estimated using a non-compartmental method. The mean (+/- SD) peak concentration was 8341 +/- 3132 microg/L at 17.5 +/- 5.0 min after the start of the infusion, and doxorubicinol concentrations declined biexponentially to 154.3 +/- 34.5 microg/L, 40 min after the end of the infusion. Systemic clearance was 0.940 +/- 0.473 L/h/kg, mean residence time was 0.165 +/- 0.133 h, and steady-state volume of distribution was 0.123 +/- 0.0526 L/kg. The terminal half-life was 0.660 +/- 0.611 h. Detectible but unquantifiable concentrations of doxorubicinol were present in the plasma ultrafiltrate of two birds during the infusion, indicating very extensive plasma protein binding. Physiological, haematological and biochemical monitoring over 3 weeks showed that doxorubicinol at a single infused dose of 2 mg/kg caused no toxicities of major concern.

Suspected fibrocartilaginous embolism in a cat.

A 12-year-old cat was presented to the University of Queensland's Small Animal Teaching Hospital with a 1-day history of left hemiparesis of acute onset, with no evidence of trauma or toxin exposure. Neurological examination findings were consistent with a lesion in the caudal left cervical spinal cord (C6 to C8), which was non-painful and had not progressed since the onset of clinical signs. No other abnormalities were found, although myelography showed a mild swelling involving the caudal cervical and cranial thoracic spinal segments. A diagnosis of suspected fibrocartilaginous embolism was made on the basis of the history, clinical presentation and diagnostic tests results, making this case the first report of a suspected fibrocartilaginous embolism in a cat that returned to normal function.

Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita).

OBJECTIVE: To determine the pharmacokinetics of carboplatin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. DESIGN: A pharmacokinetic study of carboplatin, following a single intravenous (IV) or intraosseus (IO) infusion over 3 min, was performed in six healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were anaesthetised and a jugular vein cannulated for blood collection. Carboplatin (5 mg/kg) was infused over 3 min by the IV route in four birds via the contralateral jugular vein, and by the IO route in two birds via the ulna. Serial blood samples were collected for 96 h after initiation of the infusion. Tissue samples from 11 organs were obtained at necropsy, 96 h after carboplatin administration. Total Pt and filterable Pt in plasma and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma data. RESULTS: The mean +/- SD for the Cmax of filterable Pt was 27.3 +/- 4.06 mg/L and in all six birds occurred at the end of the 3 min infusion, thenceforth declining exponentially over the next 6 h to an average concentration of 0.128 +/- 0.065 mg/L. The terminal half-life (T1/2) was 1.0 +/- 0.17 h, the systemic clearance (CI) was 5.50 +/- 1.06 mL/min/kg and the volume of distribution (Vss) was 0.378 +/- 0.073 L/kg. The extrapolated area under the curve (AUC0-x) was 0.903 +/- 0.127 mg/mL x min; the area extrapolated past the last (6 h) data point to infinite time averaged only 1.25% of the total AUC0-x. The kidneys had the greatest accumulation of Pt (7.04 +/- 3.006 microg/g), followed by the liver (3.08 +/- 1.785 microg/g DM). CONCLUSIONS AND CLINICAL RELEVANCE: Carboplatin infusion in sulphur-crested cockatoos produced mild, transient alimentary tract signs and the Pt plasma concentration was similar whether carboplatin was given intravenously or intraosseously. Filterable plasma Pt concentrations for carboplatin persisted longer than for cisplatin, due mostly to the difference in systemic clearance between these drugs in sulphur-crested cockatoos. The distribution of tissue Pt after carboplatin administration was similar to that reported for cisplatin in sulphur-crested cockatoos. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo shares some features with the kinetics reported previously in other animals and human beings.

Doxorubicin pharmacokinetics following a single-dose infusion to sulphur-crested cockatoos (Cacatua galerita).

OBJECTIVE: To determine the pharmacokinetics of doxorubicin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. DESIGN: A pharmacokinetic study of doxorubicin, following a single intravenous (i.v.) infusion over 20 min, was performed in four healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused i.v. over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse-phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL. Established non-parametric methods were used for the analysis of plasma doxorubicin data. RESULTS: During the infusion the mean +/- SD for the Cmax of doxorubicin was 4037 +/- 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (beta-phase) half-life was 41.4 +/- 18.5 min, the systemic clearance (CI) was 45.7 +/- 18.0 mL/min/kg, the mean residence time (MRT) was 4.8 +/- 1.4 min, and the volume of distribution at steady state (V(SS)) was 238 +/- 131 mL/kg. The extrapolated area under the curve (AUC(0-infinity)) was 950 +/- 677 ng/mL x h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate-limited pharmacokinetics of doxorubicinol. CONCLUSIONS AND CLINICAL RELEVANCE: Doxorubicin infusion in sulphur-crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half-life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.

Platinum pharmacokinetics in sulphur-crested cockatoos (Cacatua galerita) following single-dose cisplatin infusion.

OBJECTIVE: To determine the pharmacokinetics of platinum (Pt) in cockatoos. DESIGN: A pharmacokinetic study of Pt, following a single i.v. infusion of cisplatin, was done in six healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were hydrated for 1 h before and 2 h after a 1-h cisplatin infusion (1 mg/kg, i.v.). Serial blood samples were collected for 96 h after initiation of the infusion and urine was collected for 2 h during the hydration period after cisplatin administration. Tissue samples from 10 organs were obtained at necropsy, 96 h after cisplatin infusion. Total Pt and filterable Pt in plasma, urinary Pt and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma and urine data. RESULTS: For total Pt and filterable Pt, the respective mean systemic clearances were 0.373 and 0.699 L/kg hourly, the steady state volumes of distribution were 4.19 and 0.356 L/kg, and the mean residence times were 111 and 0.512 h. Total plasma Pt displayed a bi-exponential decay profile with average half-lives of 0.398 and 79.0 h, while filterable Pt had a monoexponential decay with mean half-life of 0.413 h. The renal clearance during the 2-h postinfusion period was 0.167 L/kg hourly. The kidneys had the highest Pt accumulation (4.54 micrograms/g DM). CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin infusion in cockatoos was well tolerated and Pt plasma concentrations were similar to those measured during treatment of solid tumours in human patients. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of Pt in the cockatoo shares some features with the kinetics reported previously in rodents, dogs and human beings.

Haematology of foetal sheep.

OBJECTIVE: To describe the ontogeny of blood cells throughout foetal development in sheep. DESIGN: A haematological study on blood and bone marrow from 42 sheep foetuses aged between 19 days gestation and full term. PROCEDURE: Virgin Merino ewes were mated and the developing foetuses removed surgically at different stages of gestation. Blood and bone marrow samples were collected, stained for cytological examination or processed for electron microscopy. Blood samples were also examined haematologically. Foetuses were incubated with 3H-thymidine and autoradiographed. RESULTS: During the first 4 weeks of development primitive erythroblast constituted the majority of the circulating blood cells. Definitive erythroid cells, originating in the liver, first appeared in the blood at around 27 days gestation and entirely replaced the primitive erythroblasts by 50 days gestation. Leukocyte numbers, especially lymphocyte count, increased rapidly after 49 days gestation. Erythropoiesis predominated in the marrow of all foetuses older than 70 days. In more marrow, myelopoiesis was the major activity and lymphopoiesis was not significant. CONCLUSIONS: Red blood cell numbers and haemoglobin content progressively increases during foetal development. Primitive erythroblasts are not the precursors of the definitive erythroblasts. There are no significant differences in morphological features or maturation sequence between hepatic and bone marrow erythroblasts. Myelopoiesis is a major activity of bone marrow rather than of foetal liver.

Giardia infection in budgerigars.

Budgerigars (Melopsittacus undulatus) from two different breeding colonies were found to have Giardia infection. Light microscopy, scanning electron microscopy and in-vitro and in-vivo studies confirmed the species was G psittaci. Chicks were clinically affected and showed signs of retarded growth, dehydration and diarrhoea. The faeces of adult birds treated with metronidazole in drinking water were negative for Giardia 5 days after treatment. Megabacteria were also found in adult birds but were not treated. This study extends the known host range for Giardia in Australia to include budgerigars.

Prevalence of megabacteria in budgerigar colonies.

OBJECTIVE: To measure the prevalence of megabacteria in budgerigar-breeding colonies and to evaluate possible methods to reduce the prevalence. DESIGN: A monitoring study over several years. SAMPLE POPULATION: Two budgerigar (Melopsittacus undulatus) colonies with over 300 birds each. PROCEDURE: The prevalence of megabacteria in the faeces in two budgerigar breeding colonies, colony 1 and 2, was determined by faecal examination of each bird. Following an initial survey (1990), most of the birds that were scored 2+ or more were culled and a management practice was implemented to discriminate against positive birds. Consecutive yearly surveys (1991, 1992) were conducted on the young birds bred in these colonies. The prevalence of megabacteria in colony 2 was also evaluated in 1994 and 1996 after all the birds were treated with amphotericin B administered in drinking water. RESULTS: The prevalence of megabacteria in the two colonies was significantly (P < 0.001) different. Overall the prevalence of megabacteria adjusted for colony differences was significantly higher (P < 0.025) in males compared to females. Age was not an influencing factor. After the initial survey, the prevalence in the offspring did not significantly (P > 0.05) decrease in the following two annual breeding seasons but by inference it did significantly decrease after amphotericin B treatment. CONCLUSION: The practice of culling most birds with more megabacteria in faeces and discriminating against positive birds when selecting birds for breeding or culling birds on show quality does not decrease megabacteria prevalence in the offspring. However, a reduction in prevalence does occur with administration of amphotericin B. Birds may have amphotericin B-resistant organisms and these birds need to be identified and culled.

Cochlosoma infections in finches.

OBJECTIVE: To survey finches in pet shops for Cochlosoma infection and evaluate the efficacy of antiprotozoal therapy with metronidazole or ronidazole. DESIGN: A survey of pet shop finches and drug efficacy trials. PROCEDURE: Finches in pet shops were randomly selected and their faeces examined microscopically for motile Cochlosoma sp trophozoites. Drug trials were carried out on 60 adult finches with naturally occurring infections. Body weight was measured and the faeces of each bird was examined for trophozoites at the beginning and 7 days after the end of treatment. In some birds, additional daily faecal examinations were done until three consecutive negative results were obtained. Metronidazole was administered at various dose rates by crop gavage or in drinking water to eight groups of five to ten finches each. Ronidazole was given in water for 7 days to ten finches. In addition, six finches whose faeces tested positive were necropsied and their tissues collected for histological examination. RESULTS: Motile flagellates in the faeces were identified as C anatis-like protozoa. Red-headed parrot-finches, Bengalese and Lady Gould finches were found to be most commonly infected. Cochlosoma sp was also found in the blue-faced parrot-finch, zebra finch, painted finch, nutmeg mannikin and double-barred finch. Metronidazole and ronidazole were found to be effective against Cochlosoma sp. Histological findings on infected adult finches were normal, except for the presence of numerous flagellates between the colorectal villi and cloacal mucosal folds. CONCLUSIONS: Cochlosoma anatis-like organisms can infect several species of finches and in adult finches are confined to the colorectum and cloaca. Infection in adult finches was mostly subclinical and could be treated effectively with metronidazole or ronidazole.

Heart failure in a macaw with atherosclerosis of the aorta and brachiocephalic arteries.

A female severe macaw (Ara severa) that was at least 11 years old was evaluated for sudden onset of exercise intolerance and dyspnea. Radiography revealed a large heart silhouette, an increase in prominence of the brachiocephalic arteries, and a diffuse increase in opacity of the lungs. Lateral nonselective angiography revealed dilatation of both chambers of the right side of the heart and incomplete emptying of the right atrium. Alterations in the shape and position of the left-side heart chambers and reduction in blood flow through the brachiocephalic arteries and aorta were identified. Despite treatment, the bird died suddenly 2.5 months after the first episode of dyspnea. At necropsy, severe atherosclerosis of the aorta and brachiocephalic arteries, dilatation of all heart chambers, pulmonary edema, and severe hepatic centrolobular atrophy and fibrosis were identified. Correlation between the angiography and necropsy findings suggested that angiography could be an important diagnostic tool for the detection of cardiovascular disease in birds.

Interaction of norfloxacin with divalent and trivalent pharmaceutical cations. In vitro complexation and in vivo pharmacokinetic studies in the dog.

The formation constants of the fluoroquinolones norfloxacin and ciprofloxacin with Mg2+ (log beta 1 = 2.97(4), log beta 2 = 5.6(2)), Zn2+ (log beta 1 = 3.77(2), log beta 2 = 7.59(3)), and Fe2+ (log beta 1 = 3.99(5), log beta 2 = 7.2(5)) were determined by potentiometric titration. The pH at which precipitation occurred in the titration solutions was compared for the metal ions Ca2+, Mg2+, Zn2+, Fe2+, Cu2+, and Al3+. The formation constants were used to predict a rank order of metals that may be expected to hinder the gastrointestinal absorption of the fluoroquinolones, in vivo. The effects of metal ions on the pharmacokinetics of orally-administered norfloxacin in the dog were investigated. Norfloxacin (12 mg/kg) was administered alone or with equimolar doses of each of the chloride salts of Ca2+, Mg2+, Zn2+, Fe2+, and Al3+. Statistically significant reductions in serum norfloxacin concentrations were observed after analysis by HPLC. The Cmax was reduced 29-85%, while the area under the norfloxacin serum concentration-time curve (AUC0-infinity) was reduced by 29-79%. The extent of the reduction in AUC0-infinity was correlated with the magnitude of the formation constant of the 1:1 norfloxacin:metal chelate complex for the divalent metal ions. On coadministration of 12 mg/kg norfloxacin with various doses of Mg2+ (chloride) the AUC0-infinity and Cmax decreased with increasing Mg2+ dose. The interaction peaked at a Mg2+:norfloxacin ratio of 1:2 suggesting the formation of a 1:2 Mg:norfloxacin complex. Formation constant data were used to simulate the percentage of norfloxacin complexed at pH 6.5. Combinations of metal ion and norfloxacin which result in only a small extent (< 20%) of norfloxacin complex formation can result in relatively large decreases in oral bioavailability of this antimicrobial agent.

Rumen involvement in sheep tannic acid metabolism.

Tannic acid (TA) metabolism was studied in sheep after p.o., intra-abomasal and i.p. administration. TA and its phenolic metabolites in ruminal fluid, abomasal fluid, plasma and urine were determined using high-performance liquid chromatography at various intervals post-dosing. After po administration, gallic acid (GA) and pyrogallol (PYR) were present in ruminal fluid and plasma, and GA, PYR and 4-O-methyl gallic acid (40MGA) were found in urine. The concentration of GA in ruminal fluid and urine gradually decreased after dosing, while PYR concentration continued to rise. By contrast, after intra-abomasal dosing, GA and ellagic acid (EA) as well as TA were found in abomasal fluid, GA, 40MGA, EA and TA were present in plasma, and GA, 40MGA and PYR were in urine. The latter 3 metabolites were also detected in the urine after ip administration of TA. The plasma concentration of TA after intra-abomasal administration was significantly correlated with liver necrosis, and PYR concentration in ruminal fluid following po administration was significantly correlated to blood methemoglobin level. It was concluded that the methemoglobinemia seen in sheep given TA po is caused by high levels of the phenolic metabolite PYR, which is produced in the rumen. Liver and kidney necrosis, seen in sheep given TA directly into the abomasum, appears caused by unmetabolized TA rather than by metabolites.

Acute intra-abomasal toxicity of tannic acid in sheep.

Acute tannic acid toxicity was studied in 6 adult Merino ewes by administering 7-10% (w/v) tannic acid solution once into the abomasum via an abomasal fistula at dose rates of 0.5, 1.0 or 2.0 g tannic acid/kg body weight. Samples of blood, urine and abomasal fluid were collected over a 48-h period before the sheep were necropsied 48 h after dosing. Dose rates of 1.0 and 2.0 g tannic acid/kg body weight produced abomasal, liver and kidney lesions. The abomasum had superficial mucosal erosions, hemorrhage and submucosal edema; the liver showed midzonal or periacinar coagulative necrosis; and the kidneys had focal tubular vacuolation and necrosis. In sheep dosed with 1.0 g tannic acid/kg body weight, there was a significant (P < 0.01) decrease in plasma phosphate and an increase in plasma aspartate aminotransferase and urea levels. Plasma total protein concentrations significantly (P < 0.05) decreased 24 h after dosing, but returned to normal by 48 h. By 4 h after dosing, abomasal fluid pH was significantly (P < 0.01) higher than predosing value, whereas urine pH significantly (P < 0.05) decreased. Both abomasal fluid and urine pH returned to normal 48 h after dosing. The liver and kidney damage seen in this study, in contrast to the methemoglobinemia without liver and kidney lesions previously reported when sheep were given tannic acid by oral gavage (1), suggest that, in cases of natural poisoning, tannins are not released from plant material until it enters the abomasum.