Chronic ingestion of high concentrations of cholecalciferol in cats

OBJECTIVE: To determine whether ingestion of 63 times the recommended amount of vitamin D3 (cholecalciferol) results in renal calcification or damage in cats. ANIMALS: 20 four-month-old kittens, 17 queens, and 20 kittens born to these queens. PROCEDURE: 4-month-old kittens and queens were given a purified diet with 846 microg of cholecalciferol/kg of diet (high vitamin D3 diet) or 118 microg of cholecalciferol/kg of diet (control diet) for 18 months. Kittens born to queens were weaned onto the same diet given to dams. RESULTS: There were no apparent adverse effects of the high vitamin D3 diet. Plasma cholecalciferol and 25-hydroxycholecalciferol (25-OHD3) concentrations of queens and 4-month-old kittens given the high vitamin D3 diet significantly increased with time. At 6 months, plasma cholecalciferol concentrations in these kittens and queens were 140.0+/-7.3 nmol/L and 423.6+/-26.6 nmol/L, respectively (10 times initial values). Corresponding 25-OHD3 concentration in queens was 587.5+/-59.4 nmol/L (2.5-fold increase over initial values). At 3 months of age, kittens born to queens given the high vitamin D3 diet had an increase in serum BUN and calcium concentrations and a decrease in RBC and serum total protein, albumin, and hemoglobin concentrations. By 18 months, these kittens had an increase in plasma cholecalciferol (276.0+/-22.2 nmol/L) and 25-OHD3 (1,071.9+/-115.3 nmol/L) concentrations. However, all indices of renal function and the appearance of renal tissue on histologic evaluation were normal. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that cats are resistant to cholecalciferol toxicosis when the diet is otherwise complete and balanced.     

Effects of ergosterol on bone mineralisation in chicks given cholecalciferol or ergocalciferol.

Groups of chicks were given diets containing cholecalciferol or ergocalciferol supplemented with 0, 0-1, 1 or 10 g ergosterol/kg. 2. Ergosterol had no significant effect on growth, on the plasma concentration of calcium or on the content of bone-ash, indicating that it did not impair the absorption of either form of vitamin D. 3. An explanation is given for the apparent disagreement in the published findings on the relative anti-rachitic potencies of ergocalciferol and cholecalciferol in the chick.     

Feeding 25-hydroxyvitamin D3 to improve beef tenderness

The objective of this trial was to determine if a single oral bolus of 25-hydroxyvitamin D3 (25-OH D3) given at various times before slaughter would enhance the tenderness of beef loin steaks. One hundred eight crossbred steers were allotted to 18 pens so that the mean weight of the cattle in each pen was similar. Treatments (25-OH D3 dose [62.5 or 125 mg]) and time of administration of the single oral bolus (4, 7, 21, or 35 d before slaughter) were assigned randomly to each pen of steers. Serial plasma samples were collected at each bolus administration time for control animals. For steers assigned to a treatment group, a baseline blood sample was collected before bolus administration and at each subsequent administration when other treatment groups received their bolus. Plasma samples were assayed for 25-OH D3 and calcium concentrations. Troponin-T degradation and Warner-Bratzler shear force were measured as indicators of tenderness for loin steaks collected at slaughter and aged for 6 or 14 d postmortem. Muscle samples, collected concurrently, were assayed for 25-OH D3 and calcium concentrations. A single oral bolus of 25-OH D3 was sufficient to increase plasma 25-OH D3 concentrations (P < 0.001) through slaughter, regardless of dose or time of bolus administration. The single oral bolus of 25-OH D3, however, did not increase plasma calcium concentrations (P > 0.05). As a result, neither troponin-T degradation nor Warner-Bratzler shear force was improved (P > 0.05) by treatment. Muscle 25-OH D3 concentrations were increased (P > 0.001) by treatment with 25-OH D3. Although sustained plasma 25-OH D3 concentrations did not increase plasma or muscle calcium at slaughter nor influence tenderness, the use of 25-OH D3 as a nutritional means of improving beef tenderness is in its infancy, and more research to delineate an effective dose and the potential interaction of seasonal exposure to ultraviolet light is warranted.     

Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats

OBJECTIVE: To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats. ANIMALS: 7 healthy neutered male client-owned cats. PROCEDURES: Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration. RESULTS: 2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 +/- 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 +/- 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 +/- 142 ng/mL and 62.4 +/- 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.     

Plasma and milk concentrations of vitamin D3 and 25-hydroxy vitamin D3 following intravenous injection of vitamin D3 or 25-hydroxy vitamin D3.

Plasma levels of vitamin D3 or 25-hydroxyvitamin D3 in ewes after administration of a single massive intravenous dose of vitamin D3 (2 X 10(6) IU) or 25-hydroxy vitamin D3 (5 mg) were determined at zero, one, two, three, five, ten and 20 days postinjection. In six ewes injected with vitamin D3 conversion of vitamin D3 to 25-hydroxy vitamin D3 resulted in a six-fold increase in the plasma 25-hydroxy vitamin D3 level within one day. Elevated levels were maintained until day 10 but by day 20 a substantial decline in the plasma 25-hydroxy vitamin D3 level had occurred. Peak levels of vitamin D3 were reached one day after injection and then continuously declined until day 20. Administration of 25-hydroxy vitamin D3 increased plasma concentrations of 25-hydroxy vitamin D3 to fivefold higher levels than those observed when vitamin D3 was injected, with approximately threefold higher levels of 25-hydroxy vitamin D3 maintained for five days. On day 10 and day 20 ewes which were injected with 25-hydroxy vitamin D3 still maintained plasma levels of 25-hydroxy vitamin D3 which were twice as high as those of ewes injected with vitamin D3. In six ewes injected with vitamin D3, a sharp increase in vitamin D3 level in milk occurred within one day and more than a tenfold elevation of milk vitamin D3 concentrations were maintained for ten days. By 20 days the milk vitamin D3 level had returned to preinjection levels. These observations suggest that indirect supplementation of the suckling ruminant with vitamin D3 may be achieved through maternal injection and subsequent mammary transfer.     

Providing vitamin D to confined sheep by oral supplementation vs ultraviolet irradiation

Serial vitamin D3 (D3) and 25-hydroxyvitamin D3 (25 OH D3) concentrations of plasma were measured in confined, shorn sheep that had either been supplemented with vitamin D3 (50 micrograms/d) or exposed daily to ultraviolet irradiation (UVI). In the sheep administered D3 orally, plasma D3 increased continuously until d 35. This was followed by small fluctuations of the plasma D3 concentrations until a plateau was reached after 56 d of supplementation (.94 ng/ml plasma). Plasma 25 OH D3 concentrations increased continuously and plateaued between d 65 to 75 at about 21 ng/ml plasma. In the UVI sheep, plasma D3 and 25 OH D3 concentrations increased continuously for the first 49 d, then plateaued at 2.03 ng D3 and 29.6 ng 25 OH D3/ml. When a plateau was reached in plasma 25 OH D3 concentrations in both treatment groups, a 3H-labeled tracer dose of 25 OH D3 was given i.v., and disappearance of the 3H-labeled 25 OH D3 was followed. The UVI group had a faster decline in specific activities during the first exponential phase but a slower decline during the prolonged terminal elimination phase. These differences are reflected in the intercompartmental transfer rates. Our data indicate that UVI is as effective as oral vitamin D3 supplementation for improving vitamin D status of confined sheep.     

Plasma homocysteine, B vitamins, and amino acid concentrations in cats with cardiomyopathy and arterial thromboembolism

Arterial thromboembolism (ATE) is a common complication of cats with cardiomyopathy (CM), but little is known about the pathophysiology of ATE. In people, high plasma concentrations of homocysteine and low B vitamin concentrations are risk factors for peripheral vascular disease. In addition, low plasma arginine concentrations have been linked to endothelial dysfunction. The purpose of this study was to compare concentrations of homocysteine, B vitamins, and amino acids in plasma of normal cats to those of cats with CM and ATE. Plasma concentrations of homocysteine, vitamin B6, vitamin B12, folate, and amino acids were measured in 29 healthy cats, 27 cats with CM alone, and 28 cats with both CM and ATE. No differences were found between groups in homocysteine or folate. Mean vitamin B12 concentration (mean +/- standard deviation) was lower in cats with ATE (866 +/- 367 pg/mL) and cats with CM (939 +/- 389 pg/mL) compared with healthy controls (1,650 +/- 700 pg/mL; P < .001). Mean vitamin B6 concentration was lower in cats with ATE (3,247 +/- 1.215 pmol/mL) and cats with CM (3,200 +/- 906 pmol/mL) compared with healthy control animals (4,380 +/- 1,302 pmol/mL; P = .005). Plasma arginine concentrations were lower in cats with ATE (75 +/- 33 nmol/mL) compared with cats with CM (106 +/- 25 nmol/mL) and healthy control animals (96 +/- 25 nmol/ mL; P < .001). Vitamin B12 concentration was significantly correlated with left atrial size. We interpret the results of this study to suggest that vitamin B12 and arginine may play a role in CM and ATE of cats.     

Evaluation of transdermal application of glipizide in a pluronic lecithin gel to healthy cats

OBJECTIVE: To evaluate plasma glipizide concentration and its relationship to plasma glucose and serum insulin concentrations in healthy cats administered glipizide orally or transdermally. ANIMALS-15 healthy adult laboratory-raised cats. PROCEDURE: Cats were randomly assigned to 2 treatment groups (5 mg of glipizide, PO or transdermally) and a control group. Blood samples were collected 0, 10, 20, 30, 45, 60, 90, and 120 minutes and 4, 6, 10, 14, 18, and 24 hours after administration to determine concentrations of insulin, glucose, and glipizide. RESULTS: Glipizide was detected in all treated cats. Mean +/- SD transdermal absorption was 20 +/- 14% of oral absorption. Mean maximum glipizide concentration was reached 5.0 +/- 3.5 hours after oral and 16.0 +/- 4.5 hours after transdermal administration. Elimination half-life was variable (16.8 +/- 12 hours orally and 15.5 +/- 15.3 hours transdermally). Plasma glucose concentrations decreased in all treated cats, compared with concentrations in control cats. Plasma glucose concentrations were significantly lower 2 to 6 hours after oral administration, compared with after transdermal application; concentrations were similar between treatment groups and significantly lower than for control cats 10 to 24 hours after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Transdermal absorption of glipizide was low and inconsistent, but analysis of our results indicated that it did affect plasma glucose concentrations. Transdermal administration of glipizide is not equivalent to oral administration. Formulation, absorption, and stability studies are required before clinical analysis can be performed. Transdermal administration of glipizide cannot be recommended for clinical use at this time.     

Effects of oral administration of "rumen-bypass" vitamin D3 on vitamin D and calcium metabolism in periparturient cows

Eleven late-pregnant Jersey cows were assigned to two groups; a group (PO-RBVD group) consisting of five cows treated with an oral administration of 10 million I.U. of an encapsulated form of vitamin D3 ("rumen-bypass" VD3; RBVD3) and another group (IMVD group) consisting of the other six treated with an intramuscular injection of 10 million I.U. of vitamin D3 (VD3). The cows received the RBVD3 or VD3 administration at 7 days before the expected parturition. The changes in the plasma concentrations of vitamin D metabolites, ionized Ca (Ca++) and inorganic phosphorus (iP) were evaluated. Of the vitamin D metabolites, the plasma 25-hydroxyvitamin D concentrations in PO-RBVD group increased significantly after the RBVD3 administration and remained in high levels that were significantly higher than those in IMVD group. This suggested that RBVD3 was absorbed rapidly and excellently from the post-ruminal digestive tract without the degradation by ruminal microorganisms. The plasma Ca++ and iP concentrations in PO-RBVD group tended to be higher after the administration and around parturition than those in IMVD group. From these observations, it was suggested the oral RBVD3 administration had more potent ability to prevent parturient paresis compared with the VD3 injection used widely in Japan.     

Use of 25-hydroxyvitamin D3 and vitamin E to improve tenderness of beef from the longissimus dorsi of heifers

The objective of this trial was to determine whether a single bolus of 25-hydroxyvitamin D(3) (25-OH D(3)), vitamin E, or a combination of the 2 would improve the tenderness of steaks from the LM of beef heifers. Forty-eight Angus crossbred heifers were allotted randomly to 8 pens. Six heifers were in each pen, and there were 2 pens per treatment. The 4 treatments included control (no 25-OH D(3) or vitamin E); 25-OH D(3) (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter); vitamin E (1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter); or combination (500 mg of 25-OH D(3) administered as a one-time oral bolus 7 d before slaughter and 1,000 IU of vitamin E administered daily as a top-dress for 104 d before slaughter). Blood samples were obtained on the day that heifers were allotted to treatments, on the day 25-OH D(3) was administered, and on the day before slaughter. Plasma calcium concentration was increased when 25-OH D(3) was administered with or without vitamin E (P < 0.007). In LM, calcium concentration tended to increase (P = 0.10) when 25-OH D(3) was administered alone but not when 25-OH D(3) was administered with vitamin E. Concentrations of 25-OH D(3) and 1,25-dihydroxyvitamin D(3) in plasma were increased when 25-OH D(3) was administered with or without vitamin E (P < 0.001). Steaks from heifers treated with 25-OH D(3) or vitamin E, but not both, tended to have lower Warner-Bratzler shear force than steaks in the control group at 14 d postmortem (P = 0.08). Postmortem protein degradation as measured by Western blot of the 30-kDa degradation product of troponin-T was increased with all treatments after 3 d postmortem (P 相似文献   

Kinetic behavior of three preparations of alpha-tocopherol after oral administration to postpubertal heifers

OBJECTIVE: To assess the kinetic behavior of 3 preparations of alpha-tocopherol (vitamin E) after oral administration to heifers. ANIMALS: 8 postpubertal Friesian heifers. PROCEDURE: A single oral bolus of 5,000 U of alpha-tocopherol in oil or encapsulated in liposomes or cyclodextrin was administered to each cow, using a 4 X 4 design with 8 days between treatments. Blood samples for kinetic analyses were obtained at various times for 168 hours after treatment. RESULTS: Mean (+/- SEM) maximal plasma concentrations of alpha-tocopherol were 4.86 +/- 0.49 microg/ml, 5.03 +/- 0.39 microg/ml, and 5.08 +/- 0.56 microg/ml after administration of oil, liposomal, and cyclodextrin preparations, respectively. Plasma concentrations peaked 21 to 34 hours after administration. The disappearance rate constant (Kd) was less after administration of alpha-tocopherol encapsulated in liposomes, compared with the other 2 preparations. Area under the concentration versus time curve was greater after administration of either encapsulated form of alpha-tocopherol, compared with alpha-tocopherol in oil, but these differences were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The lower Kd determined for alpha-tocopherol encapsulated in liposomes suggests that this formulation may result in longer persistance of the vitamin in plasma than the other 2 preparations. Dietary supplementation with alpha-tocopherol encapsulated in liposomes may enhance plasma availability of this vitamin in cattle and could be useful during periods of increased vitamin E requirements, such as parturition and early stages of life.     

Effects of intravenous administration of lidocaine on the thermal threshold in cats

OBJECTIVE: To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. ANIMALS: 6 cats. PROCEDURE: 2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination. RESULTS: In experiment 2, actual plasma lidocaine concentrations were 0.00 +/- 0.00 microg/mL, 0.25 +/- 0.18 microg/mL, 0.57 +/- 0.20 microg/mL, 1.39 +/- 0.13 microg/mL, 2.33 +/- 0.45 microg/mL, and 4.32 +/- 0.66 microg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 microg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.     

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.     

Effects of ultraviolet radiation on plasma 25-hydroxyvitamin D3 concentrations in corn snakes (Elaphe guttata)

OBJECTIVE: To determine whether corn snakes exposed to UVB radiation have increased plasma 25-hydroxyvitamin D3 concentrations, compared with control snakes. ANIMALS: 12 corn snakes (Elaphe guttata). PROCEDURES: After an acclimation period in individual enclosures, a blood sample was collected from each snake for assessment of plasma 25-hydroxyvitamin D3 concentration. Six snakes were provided with no supplemental lighting, and 6 snakes were exposed to light from 2 full-spectrum coil bulbs. By use of a radiometer-photometer, the UVA and UVB radiation generated by the bulbs were measured in each light-treated enclosure at 3 positions at the basking surface and at 2.54 cm (1 inch) below each bulb surface; the arithmetic mean values for the 3 positions at the basking surface and each individual bulb surface were calculated immediately after the start of the study and at weekly intervals thereafter. At the end of the study (day 28), another blood sample was collected from each snake to determine plasma 25-hydroxyvitamin D3 concentration. RESULTS: Mean +/- SD plasma concentration of 25-hydroxyvitamin D3 in snakes that were provided with supplemental lighting (196 +/- 16.73 nmol/L) differed significantly from the value in control snakes (57.17 +/- 15.28 nmol/L). Mean exposure to UVA or UVB did not alter during the 4-week study period, although the amount of UVA recorded near the bulb surfaces did change significantly. CLINICAL RELEVANCE: These findings have provided important insight into the appropriate UV radiation requirements for corn snakes. Further investigation will be needed before exact husbandry requirements can be determined.     

Effect of vitamin D supplementation during pregnancy on the vitamin D status of ewes and their lambs

Pregnant ewes were injected intramuscularly with 300,000 iu of vitamin D3 in a water miscible vehicle either 10, seven or four weeks before the expected lambing date and the effects on plasma concentrations of 25-hydroxyvitamin D3 were monitored. The concentrations increased quickly and remained high at parturition but at no time were they outside the normal physiological range. The concentrations in the plasma of the newborn lambs were higher than in uninjected controls and were well correlated with the concentrations in their mothers. Dosing pregnant ewes with 300,000 iu of vitamin D3 in a rapidly available form, approximately two months before lambing, provided a safe means of increasing the vitamin D status of the ewe and the newborn lamb by preventing the seasonally low concentrations of 25-hydroxyvitamin D3.     

Pharmacokinetics of cetirizine in healthy cats

OBJECTIVE: To develop a high-performance liquid chromatography (HPLC) assay for cetirizine in feline plasma and determine the pharmacokinetics of cetirizine in healthy cats after oral administration of a single dose (5 mg) of cetirizine dihydrochloride. ANIMALS: 9 healthy cats. PROCEDURES: Heparinized blood samples were collected prior to and 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after oral administration of 5 mg of cetirizine dihydrochloride to each cat (dosage range, 0.6 to 1.4 mg/kg). Plasma was harvested and analyzed by reverse-phase HPLC. Plasma concentrations of cetirizine were analyzed with a compartmental pharmacokinetic model. Protein binding was measured by ultrafiltration with a microcentrifugation system. RESULTS: No adverse effects were detected after drug administration in the cats. Mean +/- SD terminal half-life was 10.06 +/- 4.05 hours, and mean peak plasma concentration was 3.30 +/- 1.55 microg/mL. Mean volume of distribution and clearance (per fraction absorbed) were 0.24 +/- 0.09 L/kg and 0.30 +/- 0.09 mL/kg/min, respectively. Mean plasma concentrations were approximately 2.0 microg/mL or higher for 10 hours and were maintained at > 0.72 microg/mL for 24 hours. Protein binding was approximately 88%. CONCLUSIONS AND CLINICAL RELEVANCE: A single dose of cetirizine dihydrochloride (approx 1 mg/kg, which corresponded to approximately 0.87 mg of cetirizine base/kg) was administered orally to cats. It was tolerated well and maintained plasma concentrations higher than those considered effective in humans for 24 hours after dosing. The half-life of cetirizine in cats is compatible with once-daily dosing, and the extent of protein binding is high.     

Distribution of orally administered trimethoprim and sulfadiazine into noninfected subcutaneous tissue chambers in adult ponies

The distribution of trimethoprim (TMP) and sulfadiazine (SDZ) into subcutaneously implanted noninfected tissue chambers was studied in healthy adult ponies. Six ponies were given an oral TMP/SDZ paste formulation at a dose of 5 mg/kg TMP and 25 mg/kg SDZ at 12 h intervals for 2 days in order to reach steady-state concentrations. Plasma concentrations and tissue chamber fluid (TCF) concentrations of both drugs were measured at regular intervals during a period commencing 24 h after the last oral administration. The peak concentration of TMP (mean +/- SD) was 2.92 +/- 0.86 microg/mL for plasma and 1.09 +/- 0.25 microg/mL for TCF. For SDZ, the mean peak concentration was 40.20 +/- 14.74 microg/mL for plasma and 23.48 +/- 5.84 microg/mL for TCF. TMP peak concentrations in plasma were reached at 3.17 +/- 03.48 h and those in TCF at 7.33 +/- 03.72 h. SDZ peak concentrations in plasma were reached at 1.83 +/- 02.04 h and those in TCF at 8.00 +/- 03.10 h. Concentrations of TMP and SDZ in TCF remained above the generally accepted breakpoint for susceptibility (0.5/9.5 for the TMP/SDZ combination) for 12 h. Therefore, in ponies oral administration of TMP/SDZ at a dose rate of 30 mg/kg given twice daily in the form of a paste should be appropriate for effective treatment of infections caused by susceptible bacteria.     

Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats

OBJECTIVE: To determine pharmacokinetics of troglitazone in healthy cats after i.v. and oral administration of a single dose of the drug. ANIMALS: 5 healthy ovariohysterectomized adult cats. PROCEDURE: Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight i.v. and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography. RESULTS: Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 +/- 0.1 hours. Steady-state volume of distribution was 0.23 +/- 0.15 L/kg. After i.v. administration, clearance was 0.33 +/- 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%. CONCLUSIONS AND CLINICAL RELEVANCE: The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans.     

Tolerance and pharmacokinetics of cephalexin in cats after oral administration

The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.     

Digestion of bentiromide and absorption of xylose in healthy cats and absorption of xylose in cats with infiltrative intestinal disease

The digestion of bentiromide and the absorption of D-xylose was measured in 17 clinically healthy cats. The plasma xylose concentrations of the healthy cats were compared with values from 9 cats with diffuse infiltrative intestinal disease. The cats were administered 16.7 mg of bentiromide/kg and 0.5 g of xylose/kg via a stomach tube. Plasma samples were obtained before administration and 30, 60, 90, and 120 minutes after administration. The maximum mean plasma p-aminobenzoic acid concentration occurred at 60 minutes, with a value of 386 +/- 134 micrograms/dl (mean +/- SD). The maximum mean plasma xylose concentration also occurred at 60 minutes, with a value of 26.0 +/- 9.2 mg/dl. Plasma concentrations of p-aminobenzoic acid and xylose were lower in healthy cats than those reported for healthy dogs. There was no significant difference between xylose concentrations in healthy cats and cats with infiltrative intestinal disease.