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1.
A regime for administration of ampicillin sodium by continuous intravenous infusions to horses was designed. The aim was to achieve plasma ampicillin concentrations between 5 and 10 pgiml over a 4-h period. A 2 mgikg bodyweight loading dose of ampicillin sodium was administered intravenously at the beginning of the infusion in order to achieve steady-state plasma concentra-tions rapidly. The infusion system subsequently administered ampicillin at a rate of approximately 19.2 pglminikg bodyweight. The plasma concentrations obtained over the infusion period correlated very well with predicted calculations based on pharmacokinetic parameters. A mean ± SEM steady-state plasma concentration (Cpss) of 5.94 ± 0.33 was obtained and ampicillin was shown to have an apparent steady-state volume of distribution (Vdss) of 175.43 ± 13.63 ml/kg. When the pump was disconnected the concentrations declined over the following 4 h in an exponential way with an elimination half-life (t1/2β) of 0.62 h. In addition, three different infusion dose rates (13.78, 19.34 and 2 l 4 8 pg/min/kg) were administered to a single animal showing that a good correlation(correlation coefficient > 0.99) existed between the dose administered the steady-state plasma concentrations and the corresponding areas under the plasma concentration versus time curve.  相似文献   

2.
Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1= 0.05 ± 0.06 h-1 and ka2= 0.06 ± 0.01 h-l. Alclofenac half-lives t ½ and t 1/2β were 1.0 ± 0.8 h and 6.9 ± 1.5 h, respectively. Maximal concentrations (38.9 ± 16.2 μg/ml) were obtained after 8.5 ± 2.4 h. Alclofenac was detected in urine for at least 48 h after dosing. The percentage of the dose excreted as unchanged alclofenac in 12 h was very low (0.68 ± 0.19%), total (free + conjugated) alclofenac accounted for 2.16 ± 0.55% of the dose.  相似文献   

3.
Pharmacokinetics of chloramphenicol in the neonatal horse   总被引:1,自引:0,他引:1  
Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first-order elimination. Mean pharmacokinetic values were: zero-time serum concentration (C0) = 36.14 μg/ml (±14.80); apparent specific volume of distribution ( Vd ) = 1.614 1/kg (±0.669); and elimination rate constant ( K ) = 0.7295 h-1 (±0.3066) which corresponds to a biological half-life ( t 1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.
A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.  相似文献   

4.
Pharmacokinetics of cefoperazone in horses   总被引:1,自引:0,他引:1  
The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase ( t 1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase ( t 1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half-life of absorption was 2.51 ± 0.72 min and t 1/2(β) was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/mL, respectively.  相似文献   

5.
The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t ½β) was 23.14±1.06 h. The apparent volume of distribution ( V d(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (Ka) was 0.056±0.002 h−1 and the mean absorption half-life ( t ½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.  相似文献   

6.
Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (CS0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC90) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC0-12/MIC90 ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC0-12/MIC90 ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.  相似文献   

7.
Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle   总被引:1,自引:0,他引:1  
The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash-out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high-performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half-life values of 0.04 h and 0.58 h, Vd(ss) was 1.91 ± 0.42 1/kg, elimination half-life was 31.71 h while CI averaged 1.74 ± 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 ± 0.15. Diminazene was rapidly absorbed following i.m. administration; t ½ka was 0.60 h. Cmax, 4.68 ± 1.12 μg/ml, was attained in 10–15 min and systemic availability was 102.42 ± 7.25%. The half-life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro , diminazene was bound to bovine plasma albumin to the extent of 38.01–91.10%.  相似文献   

8.
The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t max of 1.46 ± 0.06 h. The elimination half-life ( t 1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t 1/2α, t 1/2β) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.  相似文献   

9.
Pharmacokinetic parameters which describe the distribution and elimination of sulphadimidine were determined in normal dogs and dogs in which fever was produced by an intravenous injection of escherichia and staphylococcal species of bacteria. Sulphadimidine was injected as a single intravenous bolus at the dose of 100 mg/kg and the kinetics of the drug were described in terms of the bi-exponential expression: Cp = Ae -α t + Be -β t . The distribution half-times of the drug were 1.52 h in the normal and 0.81 h in the febrile dogs. The drug distribution was significantly more rapid ( P < 0.05) in febrile than in normal dogs. Average ± SD values for the half-lives of the drug were 16.2 ± 5.7 h in normal and 16.7 ± 4.7 h in the febrile dogs. The apparent volume of distribution ( V ' d (area)) was 628 ± 251 ml/kg in the normal dogs, and was not statistically different from 495 ± 144 ml/kg in the febrile dogs. The volume of the central compartment ( V ' c ) was 445 ± 55 ml/kg in normal dogs and this was significantly higher ( P < 0.01) than the V ' c of 246 ± 72 ml/kg in the febrile dogs. The body clearance was 22.4 ± 4.8 and 20.2 ± 3.6 ml/hour. kg in the normal and febrile dogs, respectively. The investigation revealed that the dosage regimen of sulphadimidine did not differ significantly between normal and febrile dogs.  相似文献   

10.
Prostaglandin F receptors (PGF Rs) were measured in bovine corpus luteum and myometrial cell membranes using a radiometric method. The inhibition of labelled PGF binding exerted by d-cloprostenol, dl-cloprostenol, PGF and PGE1 (l0–11 M to 10–4 M) was evaluated in vitro. Results strongly suggest that cloprostenol binding to PGFRs is stereospecific. d-Cloprostenol and PGF were equipotent, about 150 times more potent than d-cloprostenol (P < 0.05) and approximately 280 times more potent than PGE, (P < 0.05) in inhibiting [3H]PGF binding to corpus luteum cell membranes. Such differences were less evident in myometrial cell membranes, where d-cloprostenol and PGF were about 10 times more potent than d-cloprostenol (P < 0.05) and approximately 95 times more potent than PGEl (P < 0.05).  相似文献   

11.
Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t 1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t 1/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [3H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.  相似文献   

12.
The aim of study was to correlate tumour necrosis factor-α (TNF) infused doses used with the TNF concentrations achieved and with the secretory function of both the ovary and the uterus in cows. We evaluated the concentrations of progesterone (P4), prostaglandin (PG)F, PGE2 nitric oxide (NO) and TNF in the jugular vein and vena cava caudalis as parameters of exogenous TNF action on the female reproductive tract. Aortae abdominalis of cows (n = 18) were infused with saline or two doses of TNF (luteolytic – 1 μg or luteotrophic – 10 μg). In the peripheral blood, 1 μg TNF concentrations achieved within the range of 30–45 pg/ml, and 10 μg TNF provoked a sharp increase in achieved concentrations at a range of 250–450 pg/mL). The TNF concentrations achieved in vena cava caudalis were five to six times higher than that in peripheral blood (p < 0.001). One microgram TNF increased PGF and NO (p < 0.001) and decreased P4 (p < 0.05). The higher TNF dose stimulated P4 and PGE2 (p < 0.01). TNF infusion at luteolytic dose achieved its concentrations at the physiological range previously observed in cows. Luteotrophic TNF dose achieved the concentrations in vena cava caudalis that are much higher than physiological level and were previously noted in pathological circumstances (i.e. mastitis , metritis ).  相似文献   

13.
Six horses were administered either 15 or 20 mg/kg body weight (b.w.) procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasma concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA plasma concentrations could be described by a one-compartment model with a t ½ of 3.49 ± 0.61 h. The total body clearance of PA was 0.395 ± 0.090 1/hr/kg and the volume of distribution was 1.93 ± 0.27 l/kg. As observed after PA administration, NAPA (an active metabolite) had a t ½ longer than PA of 6.31 ± 1.49 h. Peak NAPA concentrations (1.91 ± 0.51 μg/ml) occurred at 5.2 h after the PA i.v. dose. The ratio of area under the curves for NAPA to PA was 0.46 ± 0.15 which is similar to that expected in humans classified as slow acetylators. Percentage change in the QT interval was examined with respect to PA and PA + NAPA plasma concentrations. For PA, %ΔQT = 41.2 log (PA) - 13.26 and correlations ( r ) ranged from 0.77 to 0.91 among the horses. In the case of PA + NAPA,%ΔQT= 57.3 log(PA+NAPA)-31.83 andrangedfrom0.77to0.90. No evidence of toxicity was noted with respect to changes in the PR interval.  相似文献   

14.
α2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the α2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α2-adrenoceptor antagonist.  相似文献   

15.
Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t 1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t 1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t 1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t 1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.  相似文献   

16.
Flunixin meglumine (FM) was administered either orally as granules or intravenously to six heifers in a two period crossover study. Single doses of 2.2 mg/kg body weight were used. Pharmacokinetic variables were calculated using statistical moment methods. The effect exerted by flunixin was measured as changes in the basal plasma concentration of the main metabolite of prostaglandin (PG) F. After oral FM the arithmetic means of pharmacokinetic variables were: MRT = 12.7 h; MAT = 6.3 h; C max= 0.9 μg/mL; t max= 3.5 h. The bioavailability was 60% and the mean half-life (harmonic mean) was 6.2 h. Oral administration of FM inhibited as effectively as intravenous administration the prostaglandin biosynthesis. The concentration of the PG metabolite decreased almost as rapidly as after intravenous administration. The duration of the effect was prolonged and the PG metabolite concentration was significantly lower between 10 and 30 h after oral than after intravenous administration. The results indicate that oral dosing of flunixin, in the form of granules, can be an alternative to intravenous administration for therapeutic use in cattle.  相似文献   

17.
Objective  We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Twelve healthy horses aged 12 ± 6 years (mean ± SD), weighing 565 ± 20 kg, and with an equal distribution of mares and geldings.
Methods  Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg−1). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior scores returned to pre-sedation baseline values. Continuous data were analyzed over time using repeated-measures anova and noncontinuous data were analyzed using Friedman tests.
Results  There were no significant propofol dose or temporal effects on heart rate, respiratory rate, vertical head height, or jugular venous blood gases (pHv, PvO2, PvCO2). The 0.35 mg kg−1 dose caused mild sedation lasting up to 6 minutes. The 0.50 mg kg−1 dose increased sedation depth and duration, but with increased ataxia and apparent muscle weakness.
Conclusions and clinical relevance  Intravenous 0.35 mg kg−1 propofol provided brief, mild sedation in horses. Caution is warranted at higher doses due to increased risk of ataxia.  相似文献   

18.
The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study ( n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg ( n = 5) or 4.4 mg/kg ( n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases ( P <0.05) in total body clearance ( CL B; 29.2 ± 3.9 vs. 43.8 ± 8.1 mL/ h-kg) and the volume of distribution, calculated by area ( V d(area); 0.18 ± 0.05 vs. 0.25 ± 0.03 L/kg) or at steady-state ( V d(SS); 0.17±0.04 vs. 0.25 ± 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly ( P <0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.  相似文献   

19.
Luteolytic mechanisms have evolved in mammals to improve reproductive efficiency. The hormonal interactions that control the onset and progress of luteolysis are complex. They involve endocrine and paracrine signals that link the corpus luteum, uterus and posterior pituitary gland. Current concepts concerning these interactions will be examined in the five major domestic ungulate species commonly raised in Europe and North America (cattle, sheep, goats, pigs and horses). Some of these interactions are similar across species. All five depend on prostaglandin F secreted from the uterus, to induce luteolysis. Three hormones, progesterone, estradiol and oxytocin interact to regulate uterine secretion of PGF. Oxytocin is an acute stimulus for uterine PGF secretion. Progesterone and estradiol interact to regulate uterine secretary responsiveness to oxytocin. Precisely how these hormones interact varies across species.  相似文献   

20.
The effects of lipopolysaccharide ( Escherichia coli , O55:B5), administered 18 h after ovulation in the second oestrus after weaning on the hormonal profiles in 14 Swedish cross-bred (Landrace × Yorkshire) multiparous sows were studied. The endotoxin group (E-group) sows were administered with 300 ng/kg of lipopolysaccharide (LPS) whereas the control group (C-group) sows were administered 5 ml of saline intravenously via an indwelling jugular cannula. Blood samples for hormonal analyses were collected from all sows until slaughter. In the E-group, progesterone, cortisol and prostaglandin F metabolite levels increased significantly (p < 0.05) following LPS compared with the C-group. It can be concluded from this study that apart from elevating cortisol and prostaglandin F metabolite, LPS also elevates progesterone levels.  相似文献   

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