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1.
The purpose of the current study was to investigate the suitability of an isobaric laparoscopic procedure, using a single port, for obtaining serial kidney and liver biopsy samples from standing steers. The samples were used in support of a pharmacokinetic tissue–fluid correlation study. Laparoscopic access was performed 3 times in each of 8 healthy Holstein steers, alternating from the right side to the left side and then to the right side again. The surgery was performed in standing stocks after the animals were given 3 doses of sulfadimethoxine sulfate intravenously and fasted for at least 18 h. Sedation and analgesia were achieved with acepromazine and xylazine. Lidocaine 2% was injected at the center of the paralumbar fossa (left or right), and an incision was made for introduction of a trocar–cannula assembly. Room air was allowed to enter the abdomen through the cannula at the time of insertion. Once the peritoneal cavity was reached, an operating endoscope was inserted. No pressurized insufflation was performed. A biopsy forceps was introduced into the operating channel of the endoscope to obtain a 100-mg kidney or liver sample. No complications were encountered. The 24 laparoscopic procedures provided 24 kidney and 16 liver samples. The results suggest that the isobaric (gasless) single-port laparoscopic technique is feasible for kidney and liver biopsy on standing steers. The procedure can be performed in a reliable and efficient manner in the sedated standing bovine.  相似文献   

2.
The pharmacokinetic disposition and bioavailability of florfenicol (FF) were determined after single intravenous (i.v.) and intramuscular (i.m.) administrations of 25 mg/kg b.w. to ten healthy New Zealand White rabbits. Plasma FF concentrations were determined by high-performance liquid chromatography (HPLC). The plasma pharmacokinetic values for FF were best described by a one-compartment open model. The elimination half-life (t1/2β) was different (p < 0.05) however, the area under curve (AUC) was similar (p > 0.05) after i.v. and i.m. administrations. FF was rapidly eliminated (t1/2β 1.49 ± 0.23 h), slowly absorbed and high (F, 88.75 ± 0.22%) after i.m. injection. In addition, FF was widely distributed to the body tissues (Vss 0.98 ± 0.05 L/kg) after i.v. injection. In this study the time that plasma concentration exceeded the concentration of 2 μg/mL was approximately 6 h. For bacteria with MIC of 2 μg/mL, frequent administration at this dose would be needed to maintain the concentration above the MIC. However, it is possible that rabbit pathogens may have MIC values less than 2 μg/mL which would allow for less frequent administration. Further studies are necessary to identify the range of MIC values for rabbit pathogens and to identify the most appropriate PK-PD parameter needed to predict an effective dose.  相似文献   

3.
Colistin is an antimicrobial drug of the polymyxin group and COLIVET SOLUTION is an aqueous solution containing colistin sulphate (2 × 106 IU/mL), formulated for oral administration. The target species is the pig, particularly the suckling and post weaning animal. This investigation was undertaken to provide pharmacokinetic and pharmacodynamic data on which to base the selection of dosage rate and interval of the solution for the treatment of porcine colibacillosis.Colistin absorption from the gastrointestinal tract of young pigs, when administered at dosage rates of 25,000, 50,000 and 1,00,000 IU/kg, was slight or absent. The drug was therefore restricted almost entirely to the required site of action. The colistin concentration-time profile within the jejunum and ileum was established, and this enabled determination of the pharmacokinetic variables, maximum concentration (Cmax) and area under curve (AUC) and derivation of the surrogate indices of antibacterial activity, Cmax/minimum inhibitory concentration (MIC) and AUC/MIC through integration of in vivo data with the results of in vitro potency studies for four strains of Escherichia coli.In the in vitro bacterial growth inhibition studies colistin acted by a concentration-dependent killing mechanism. Numerical values for the surrogate parameter AUC/MIC producing bactericidal and eradication effects of colistin against four strains of E. coli were established by PK-PD modeling based on the sigmoidal Emax equation. These data were used to predict a daily dosage regimen for colistin.  相似文献   

4.
PK-PD integration and modeling of marbofloxacin in sheep   总被引:1,自引:0,他引:1  
The fluoroquinolone antimicrobial drug, marbofloxacin, was administered intravenously (IV) and intramuscularly (IM) to sheep at a dose rate of 2 mg kg−1 in a 2-period cross-over study. Using a tissue cage model of inflammation, the pharmacokinetic properties of marbofloxacin were established for serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). For serum, after IV dosing, mean values for pharmacokinetic parameters were: clearance 0.48 L kg−1 h−1; elimination half-life 3.96 h and volumes of distribution 2.77 and 1.96 L kg−1, respectively, for Vdarea and Vss. After IM dosing mean values for pharmacokinetic variables were: absorption half-time 0.112 h, time of maximum concentration 0.57 h, terminal half-life (T½el) 3.65 h and bioavailability 106%. For exudate, mean T½el values were 12.38 and 13.25 h, respectively, after IV and IM dosing and for transudate means were 13.39 h (IV) and 12.55 h (IM).The in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and ex vivo time-kill curves for marbofloxacin in serum, exudate and transudate were established against a pathogenic strain of Mannheimia haemolytica. Integration of in vivo pharmacokinetic data with MIC determined in vitro provided mean values of area under curve (AUC)/MIC ratio for serum, exudate and transudate of 120.2, 156.0 and 156.6 h after IV dosing and 135.5, 165.3 and 146.2 h after IM dosing, respectively. After IM administration maximum concentration (Cmax)/MIC ratios were 21.1, 6.76 and 5.91, respectively, for serum, exudate and transudate. The ex vivo growth inhibition data after IM administration were fitted to the sigmoid Emax (Hill) equation to provide values for serum of AUC24 h/MIC producing, bactericidal activity (22.51 h) and virtual eradication of bacteria (35.31 h). It is proposed that these findings might be used with MIC50 or MIC90 data to provide a rational approach to the design of dosage schedules which optimise efficacy in respect of bacteriological as well as clinical cures.  相似文献   

5.
The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia. The purpose of this study was to determine the pharmacokinetics and elimination pattern in urine of tramadol and its metabolites after oral administration to horses. Tramadol was administered orally to six horses and its half-life, Tmax and Cmax in plasma were 10.1, 0.59 h, and 132.7 ng/mL, respectively. The half-life, Tmax and Cmax for M1 in plasma were 4.0, 0.59 h, and 28.0 ng/mL, respectively. Tramadol and its metabolites were detectable in urine between 1 and 24 h after the administration. In conclusion, the PK data reported in this study provides information for the design of future studies of tramadol in horses.  相似文献   

6.
Pharmacokinetic and pharmacodynamic properties in goats of the non-steroidal anti-inflammatory drug tolfenamic acid (TA), administered both alone and in combination with the fluoroquinolone marbofloxacin (MB), were established in a tissue cage model of acute inflammation. Both drugs were injected intramuscularly at a dose rate of 2 mg kg−1. After administration of TA alone and TA + MB pharmacokinetic parameters of TA (mean values) were Cmax = 1.635 and 1.125 μg ml−1, AUC = 6.451 and 3.967 μg h ml−1, t1/2K10 = 2.618 and 2.291 h, Vdarea/F = 1.390 and 1.725 L kg−1, and ClB/F = 0.386 and 0.552 L kg−1 h−1, respectively. These differences were not statistically significant. Tolfenamic acid inhibited prostaglandin (PG)E2 synthesis in vivo in inflammatory exudate by 53-86% for up to 48 h after both TA treatments. Inhibition of synthesis of serum thromboxane (Tx)B2 ex vivo ranged from 16% to 66% up to 12 h after both TA and TA + MB, with no significant differences between the two treatments.From the pharmacokinetic and eicosanoid inhibition data for TA, pharmacodynamic parameters after dosing with TA alone for serum TxB2 and exudate PGE2 expressing efficacy (Emax = 69.4 and 89.7%), potency (IC50 = 0.717 and 0.073 μg ml−1), sensitivity (N = 3.413 and 1.180) and equilibration time (t1/2Ke0 = 0.702 and 16.52 h), respectively, were determined by PK-PD modeling using an effect compartment model. In this model TA was a preferential inhibitor of COX-2 (COX-1:COX-2 IC50 ratio = 12:1). Tolfenamic acid, both alone and co-administered with MB, did not affect leucocyte numbers in exudate, transudate or blood. Compared to placebo significant attenuation of skin temperature rise over inflamed tissue cages was obtained after administration of TA and TA + MB with no significant differences between the two treatments. Marbofloxacin alone did not significantly affect serum TxB2 and exudate PGE2 concentrations or rise in skin temperature over exudate tissue cages. These data provide a basis for the rational use of TA in combination with MB in goat medicine.  相似文献   

7.
It is well-known that old animals show physiologic and/or pathologic variation that could modify the pharmacokinetics of drugs and the related pharmacodynamic response. In order to define the most appropriate therapeutic protocol in old horses, pharmacokinetic profile and safety of naproxen were investigated in horses aged over 18 years after oral administration for 5 days at the dose of 10 mg/kg b.w./day. After the first administration, the maximum concentration (Cmax 44.21 ± 9.21 μg/mL) was reached at 2.5 ± 0.58 h post-treatment, the harmonic mean terminal half-life was 6.96 ± 1.73 h, AUC0–24h was 459.71 ± 69.95 h μg/mL, MRT was 7.44 ± 0.74 h and protein binding was 98.47 ± 2.72%. No drug accumulation occurred with repeated administrations. No clinical and laboratory changes were detected after administration of naproxen. Gastric endoscopies performed after the treatment did not show pathological changes of the gastric mucosa.  相似文献   

8.
The pharmacokinetic profile and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats was investigated. Single intravenous (cephalexin lysine salt) and intramuscular (20% cephalexin monohydrate suspension) were administered to five cats at a dose rate of 10 mg/kg. Serum disposition curves were analyzed by noncompartmental approaches. After intravenous administration, volume of distribution (Vz), total body clearance (Clt), elimination constant (λz), elimination half-life (t½λ) and mean residence time (MRT) were: 0.33 ± 0.03 L/kg; 0.14 ± 0.02 L/h kg, 0.42 ± 0.05 h−1, 1.68 ± 0.20 h and 2.11 ± 0.25 h, respectively. Peak serum concentration (Cmax), time to peak serum concentration (Tmax) and bioavailability after intramuscular administration were 15.67 ± 1.95 μg/mL, 2.00 ± 0.61 h and 83.33 ± 8.74%, respectively.  相似文献   

9.
The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n = 6, (2.0 mg kg−1), hydromorphone, n = 6, (0.2 mg kg−1) or a placebo of blank liposomes, n = 3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in PaCO2, PaO2, (HCO3-), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in PaCO2 (maximum (mean + SD] 44.4 + 1.1 mm of Hg) and significant decreases in PaO2 (minimum (mean + SD) 82.4 + 4.7 mm of Hg) and pH (minimum (mean + SD) 7.31 + 0.01) compared with baseline. Administration of LEH resulted in significant increases in PaCO2 (maximum (mean + SD) 44.6 + 0.9 mm of Hg) and significant decreases in PaO2 (minimum (mean + SD) 84.8 + 2.6 mm of Hg) and pH (minimum (mean + SD) 7.34 + 0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in PaCO2, PaO2, and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.  相似文献   

10.
The pharmacokinetics properties of marbofloxacin were studied in adult Eurassian Griffon vulture after single-dose intravenous (IV) administration of 2 mg/kg. Drug concentration in plasma was determined by high-performance liquid chromatography and the data obtained were subjected to compartmental and non-compartmental kinetic analysis. Marbofloxacin presented a volume of distribution at steady-state (Vdss) of 1.51 ± 0.22 L and total plasma clearance (Cl) of 0.109 ± 0.023 L/h kg. The permanence of this drug was long in vultures (T1/2λ = 12.51 ± 2.52 h; MRT = 13.54 ± 2.29 h). The optimal dose of marbofloxacin estimated is 2.73 mg/kg per day for the treatment of infections in vultures with MIC90 = 0.2 μg/mL.  相似文献   

11.
The aim of these in vivo and in vitro studies was to examine the role of ghrelin in the control of plasma hormone concentrations, the proliferation, apoptosis and secretory activity of ovarian granulosa cells and the response of these cells to hormonal treatments. Female rabbits were injected with ghrelin (10 μg/animal/day for one week before ovulation induced by 25 IU PMSG and 0.25 IU LHRH). On the day of ovulation, blood samples were collected and analyzed for concentrations of progesterone (P4), testosterone (T), estradiol (E2), estrone-sulphate (ES), insulin-like growth factor I (IGF-I) and leptin (L) by RIA. Some control and ghrelin-treated animals were killed in the periovulatory period, their ovaries were weighed and granulosa cells were isolated and cultured for 2 d. Cell proliferation (expression of PCNA) and apoptosis (expression of TdT) were evaluated by immunocytochemistry and TUNEL respectively. Secretion of P4, T, E2, IGF-I, and prostaglandin F (PGF) by granulosa cells cultured with and without LH or IGF-I (1, 10 or 100 ng/ml medium) was assessed by RIA. The remaining control and treated animals were kept until parturition, while the number, viability and body weight of pups were recorded.  相似文献   

12.
This study examined the effect of exercising horses 3 times per week with two bouts of 5-minutes' duration at their v10. Six Thoroughbreds were treadmill-conditioned for 6 weeks. A standardized exercise test (SET) was performed at the beginning of the conditioning period to determine the blood lactate–running speed (BLRS) relation, and the SET was repeated every 2 weeks. After each SET, the BLRS relation was used to calculate the horse's speed, which produced a blood lactate (LA) concentration of 10 mmol/L (v10) and 4 mmol/L (v4). Each horse was then conditioned for the next 2 weeks (3 times/week) at its individual v10 for two 5-minute bouts with a 5-minute walking phase in between. Exercise speed was individually adapted to the new v10 every 2 weeks. The v4 of horses decreased after the first 2 weeks (from 6.23 ± 0.41 m/s to 5.95 ± 0.33 m/s, mean ± SD; P < .05), increased in the following 2 weeks (6.33 ± 0.58 m/s; P < .01), and stayed constant thereafter (P > .05). The conclusion drawn was that exercising horses 3 times per week at their v10 for two 5-minute bouts did not improve v4.  相似文献   

13.
A feeding trial was conducted to evaluate the effectiveness of maifanite, which is mainly composed of aluminosilicate, in reducing the adverse effects of aflatoxin B1 (AFB1) on hematology, AFB1 residues, and antioxidant enzymes activities in weaning piglets. A total of 32 (9.28±0.17 kg BW) individually housed crossbred piglets (Duroc×Landrace×Large white) were randomly allotted to 1 of 4 dietary treatments in a 2×2 factorial arrangement with 8 replicates per treatment. The dietary treatments included 2 AFB1 levels (5.3 and 372.8 μg/kg) and 2 maifanite levels (0% and 1%). No differences in average daily gain, average daily feed intake, and gain to feed ratio were observed among treatments. Ingestion of the AFB1-contaminated (AF) diets (372.8 μg/kg of AFB1) reduced (P<0.05) the numbers of neutrophil, monocyte, and total leukocyte. There were no effects of AFB1 on gamma glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, and total protein, albumin, urea N, total bilirubin, IgG, IgA, and IgM concentrations in serum. Aflatoxin B1 was found in the liver and kidney of piglets fed the AF diets. Piglets fed the AF diets reduced (P<0.05) the total superoxide dismutase, glutathione peroxidase, and catalase activities in serum. However, total superoxide dismutase activity in the liver was increased (P<0.05) in piglets fed the AF diets compared with those fed the basal diets (5.3 μg/kg of AFB1). There was an interaction (P=0.003) in erythrocyte, but piglets fed the diets containing maifanite had greater erythrocyte and lymphocyte (P=0.035) numbers than those fed the diets without maifanite. The AFB1 levels in the liver and kidney of piglets fed the AF diet containing maifanite were 29.6% and 41.2% lower, respectively, than those of piglets fed the AF diet alone. Although there was an interaction (P=0.011), piglets fed the diets containing AFB1 and maifanite had greater serum T-SOD activity compared with those fed the diets with no maifanite. In conclusion, the addition of maifanite to the AF diet resulted in partial restoration of hematology and antioxidant enzymes activities and reduced AFB1 levels in the liver and kidney.  相似文献   

14.
This study is the first conducted in Spain to evaluate antimicrobial susceptibility of field isolates of Brachyspira hyodysenteriae. One hundred and eight isolates of the bacterium, recovered from different Spanish swine farms between 2000 and 2007, were investigated. The minimum inhibitory concentrations (MIC) of erythromycin, tylosin, tiamulin, valnemulin, clindamycin and lincomycin were determined using a broth microdilution technique. Most of the isolates showed poor susceptibility to erythromycin (MIC90 > 256 μg/ml), tylosin (MIC90 > 256 μg/ml), clindamycin (MIC90 > 4 μg/ml) and lincomycin (MIC90 = 128 μg/ml). Reduced susceptibility to tiamulin and valnemulin was observed with a MIC > 2 μg/ml in 17.6% and 7.41% of the B. hyodysenteriae isolates, respectively. Moreover, a survival analysis permitted the detection of an increasing trend in the MIC values for almost all the antimicrobials used in the treatment of swine dysentery when comparing recent isolates (from 2006 to 2007) with those recovered in earlier years (between 2000 and 2004).  相似文献   

15.
16.
The pathogenesis of GIII.2 bovine norovirus (BoNoV) is not well understood. Our study demonstrated persisting diarrhea and prolonged fecal shedding, but with a lack of significant intestinal lesions in gnotobiotic (Gn) calves infected with GIII.2 BoNoV, CV186-OH/00/US strain. Nine 4 to 7-day-old Angus/Jersey crossbred Gn calves were orally inoculated with 10.0–11.9 log10 genomic equivalents (GE)/calf of CV186-OH (n = 7) or mock (n = 2). Calves were euthanized at post-inoculation day (PID) 1 (n = 1) when moderate to severe lethargy was observed and at PIDs 2–6 (n = 4) after lethargy had subsided. Two calves were kept longer term (until PID 30) for monitoring fecal shedding patterns by TaqMan real-time RT-PCR (qRT-PCR). Most infected calves exhibited two clinical signs: (i) acute but persisting diarrhea and (ii) acute moderate to severe lethargy. The two infected calves, followed longer-term, had prolonged fecal viral RNA shedding [peak average titer of 11.8 (±0.2) log10 GE/ml] at least until PID 20. By qRT-PCR, 5 infected calves had low viral RNA titers in serum, ranging from 4.0 to 5.8 log10 GE/ml, at PIDs 1–5, but not (<2.7 log10 GE/ml) at PIDs 6–30. The latter observation coincided with the presence of serum IgG antibody to BoNoV at PIDs 8–30. Collectively, the GIII.2 BoNoV strain CV186-OH induced only mild enteropathogenicity, evident by the lack of significant intestinal lesions, but it led to persisting mild diarrhea and prolonged fecal virus shedding in Gn calves. The prolonged fecal shedding of GIII.2 BoNoV might partially explain how this virus is maintained as endemic infections in cattle.  相似文献   

17.
The pharmacokinetics of moxifloxacin were investigated in buffalo calves following a single intravenous and intramuscular administration of moxifloxacin (5 mg kg−1 body wt.). Moxifloxacin concentrations in plasma and urine were determined by microbiological assay. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by a two compartment open model, whereas intramuscular administration data were best described by a one compartment open model. Following intravenous administration, the elimination half life (t1/2β), volume of distribution (Vd(area)) and total body clearance were 2.69 ± 0.14 h, 1.43 ± 0.08 L kg−1 and 371.2 ± 11.2 ml kg−1 h−1, respectively. Following intramuscular administration, the absorption half life (t1/2ka) was 0.83 ± 0.20 h. The systemic bioavailability (F) of moxifloxacin in buffalo calves was 80.0 ± 4.08%. Urinary excretion of moxifloxacin was less than 14% after 24 h of administration of drug. In vitro binding of moxifloxacin to plasma proteins of buffalo calves was 28.4 ± 3.77%. From the data of surrogate markers (AUC/MIC, Cmax/MIC), it was determined in the buffalo calves that when administered by intravenous or intramuscular route at 5 mg kg−1, moxifloxacin is likely to be effective against bacterial isolates with MIC ? 0.1 μg ml−1.  相似文献   

18.
Breath hydrogen testing has a diagnostic potential as a gastrointestinal function test that could be performed in general practice. The purpose of this study was to improve techniques for collection of breath samples and transfer of samples to transport vessels. Breath samples from 10 dogs were collected using both a snug-fitting and a loose-fitting standard anesthetic mask attached to a reservoir bag, and a modified snug-fitting system. CO2 was used as internal standard and mean CO2 concentrations were 1.19 ± 0.76, 2.17 ± 0.66 and 2.68 ± 0.92, respectively. Additional samples were saved in transport tubes for 19 days, during which the hydrogen and carbon dioxide concentrations remained stable. A reliable method for transferring the breath samples from the reservoir bag to vacuum transport tubes was also identified. Our results demonstrate less contamination of breath samples with air than previously reported, and a reproducible method to transfer breath samples to transport vessels.  相似文献   

19.
The main purpose of the present study was to see if a kinetic model and a computer program for characterizing the rate of uptake and clearance of chemicals in aquatic organisms (Biofac, OECD’s Chemicals Testing Programme) was applicable to pharmacokinetic studies in fish. The program seems suitable for such studies.The effect of temperature upon rate of absorption of sulphadimidine from medicated water and elimination of the same drug was investigated in rainbow trout. A rise in the temperature from 7° C to 14° C more than doubled the calculated rate constants of absorption and elimination. The biological half life (t½ β) and the time to reach 90 % of steady state (t90% ss) at 14° C were approximately half the values at 7° C.  相似文献   

20.
A biopsy procedure was developed to provide serial kidney samples from standing steers. Ten clinically normal steers were given intramuscular injections of gentamicin sulfate, 4 mg/kg body weight. Renal biopsy was performed at 5 separate times. After feed was withheld for 24 h, laparoscopic surgery was performed in standing stocks. Acepromazine, xylazine, and butorphanol were used for sedation and analgesia, and 2% lidocaine was used for local anesthesia. Two incisions approximately 2 cm long were made in the paralumbar fossa to allow for trocar introduction. The abdomen was insufflated with CO2 and, with endoscopic guidance, a biopsy forceps used to remove a kidney sample 2 to 3 mm in diameter, by either a left or a right abdominal approach. Each operation was recorded on videotape, and images were also captured with a digital medical device system. Respiration, heart rate, temperature, appetite, attitude, and postural positions were evaluated at 12, 24, 48, and 72 h after surgery. The 51 laparoscopic procedures provided 48 renal samples (approximately 100 mg each). The 1st and 2nd samples were from the right kidney, and the 3rd sample was from either the left or the right kidney; the 4th and 5th samples were from the left kidney. Adhesions made an approach from the right side difficult for the 3rd sample. No clinical changes were observed in 9 steers after the procedure. One steer died after the 3rd procedure owing to hemorrhage.  相似文献   

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