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1.
Disposition of ofloxacin in female New Zealand White rabbits   总被引：2，自引：1，他引：1  
Limited information exists regarding the disposition of ofloxacin in rabbits. Pharmacokinetic information is necessary for the design of appropriate therapeutic regimens for the treatment of organisms (e.g. Pasteurella multocida ) commonly infecting this species. This study evaluated the pharmacokinetics of ofloxacin following intravenous (i.v.) and subcutaneous (s.c.) administration. Two groups of three female New Zealand White rabbits received a single dose of 20 or 40 mg/kg by the i.v. and s.c. routes. Samples were collected prior to drug administration, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h postdose. Ofloxacin concentrations in serum were determined using a validated HPLC assay. Mean maximum concentrations were 66.86 ± 10.83 mg/L and 14.1 ± 2.20 mg/L for the i.v. and s.c. administration of 20 mg/kg. The 40 mg/kg dose produced maximum concentrations of 154.96 ± 35.45 mg/L and 23.83 ± 4.01 mg/L for the i.v. and s.c. doses, respectively. The area under concentration–time curve increased proportionally with the dose, while the half-life was unaltered and ranged from 1.5–1.9 h. From these data, it appears that a 20 mg/kg dose administered every 8 h by the s.c. route would optimize the pharmacodynamic profile of ofloxacin and provide an appropriate regimen for the treatment of many susceptible organisms which commonly infect this species.  相似文献   

2.
The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration ( MIC ) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1–2 days-of-age and 4–5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1–2 day-old foals, DCA had a t ½ of 7.8 ± 0.1 h, a body clearance of 74.4 ± 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 ± 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli , Pasteurella spp, Klebsiella spp, and β-hemolytic streptococci was <0.5 μg/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates.  相似文献   

3.
Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax= 0.61 ± 0.15 μg/ml, a T max= 6 h and a t ½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax= 1.55 ± 0.11 μg/ml, T max= 8 h and 1 max= 4.28 ± 0.18 h were obtained. For the higher dose C max= 3.14 ± 0.04 μg/ml, T max= 8 h and t ½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.  相似文献   

4.
Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.  相似文献   

5.
Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC 90 for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC 90 for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.  相似文献   

6.
Pedersoli, W.M., Ravis, W.R., Jackson, J., Shaikh, B. Disposition and bioavailability of neomycin in Holstein calves. J. vet. Pharmacol. Therap. 17 , 5–11.
The disposition and absorption kinetics of neomycin were studied in healthy ruminating dairy calves ( n -6), approximately 3-months-old. The calves were treated with single intravenous (i.v.) (12 mg/kg), intramuscular (i.m.) (24mg/kg), oral (p.o.) (96 mg/kg) and repeated p.o. (96 mg/kg, b.i.d., 15½ days) doses of neomycin. A 3-week rest period was allowed between treatments A and B and B and C Baseline and serial venous blood samples were collected from each calf plasma concentrations of neomycin were determined by a high performance liquid chromatography procedure. The resulting data were evaluated by using compartmental pharmacokinetic models and nonlinear least squares regression analysis. The mean of some selected parameters were t ½λ3 7.48 ± 2.02 h, Clt= 0.25 ± 0.04 L/h/kg, V d(ss)= 1.17 ± 0.23 L/kg, and MRT = 4.63 ± 0.87 h for the i.v. data and t ½= 11.5 ± 3.8 h, MRT abs= 0.960 ± 1.001 h, F = 127 ± 35.2%, and Clt/F = 0.199 ± 0.047 L/h/kg for the i.m. data, respectively. Only one calf absorbed neomycin to any significant degree (F = 0.0042) after a single p.o. dose. Selected mean parameters determined after repeated oral dosing were: F = 0.45 ± 0.45%, Cmax= 0.26 ± 0.37 g/ml, and tmax= 2.6 ± 2.9 h. Terminal half-lives determined for the i.v. and i.m. treatments were considerably longer than those reported previously in the literature.  相似文献   

7.
Pharmacokinetics and bioavailability of doxycycline in turkeys   总被引：1，自引：0，他引：1  
The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (± SD) elimination half-life was 10.6 ± 0.7, 10.8 ± 1.5, 7.9 ± 1.4 and 10.0 ± 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (± SD) total body clearance was 0.19 (± 0.01), 0.27 (± 0.03), 0.11 (± 0.03) and 0.06 (± 0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (± 0.2), 2.1 (± 0.2), 0.7 (± 0.4) and 0.5 (± 0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day, 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 μg/mL, with t max values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the C max values were 2.5, 6.1, 4.8 and 3.0 μg/mL, with t max values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 ± 9.0% (for 12-week-old birds) and 63.5 ± 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 ± 13.0% (for 12-week-old birds) and 83.7 ± 14.3% (for 3-week-old birds).  相似文献   

8.
The minimal inhibitory concentration (MIC) of flumequine for 249 Salmonella, 126 Escherichia coli, and 22 Pasteurella multocida isolates recovered from clinical cases of neonatal calf diarrhoea, pneumonia and sudden death was less than or equal to 0.78 microgram/ml. The pharmacokinetics of flumequine in calves was investigated after intravenous (i.v.), intramuscular (i.m.) and oral administration. The two-compartment open model was used for the analysis of serum drug concentrations measured after rapid i.v. ('bolus') injection. The distribution half-life (t1/2 alpha) was 13 min, elimination half-life (t1/2 beta) was 2.25 h, the apparent area volume of distribution (Vd(area)), and the volume of distribution at steady state (Vd(ss)) were 1.48 and 1.43 l/kg, respectively. Flumequine was quickly and completely absorbed into the systemic circulation after i.m. administration of a soluble drug formulation; a mean peak serum drug concentration (Cmax) of 6.2 micrograms/ml was attained 30 min after treatment at 10 mg/kg and was similar to the concentration measured 30 min after an equal dose of the drug was injected i.v. On the other hand, the i.m. bioavailability of two injectable oily suspensions of the drug was 44%; both formulations failed to produce serum drug concentrations of potential clinical significance after administration at 20 mg/kg. The drug was rapidly absorbed after oral administration; the oral bioavailability ranged between 55.7% for the 5 mg/kg dose and 92.5% for the 20 mg/kg dose. Concomitant i.m. or oral administration of probenecid at 40 mg/kg did not change the Cmax of the flumequine but slightly decreased its elimination rate. Flumequine was 74.5% bound in serum. Kinetic data generated from single dose i.v., i.m. and oral drug administration were used to calculate practical dosage recommendations. Calculations showed that the soluble drug formulation should be administered i.m. at 25 mg/kg every 12 h, or alternatively at 50 mg/kg every 24 h. The drug should be administered orally at 30 and 60 mg/kg every 12 and 24 h, respectively. Very large, and in our opinion impractical, doses of flumequine formulated as oily suspension are required to produce serum drug concentrations of potential clinical value.  相似文献   

9.
The pharmacokinetic behaviour of sulphamethoxazole and trimethoprim was studied after combined intravenous (i.v.) administration at doses of 20 mg/kg and 4 mg/kg, respectively, and after oral administration at doses of 50 mg/kg and 10 mg/kg. The serum concentration versus time data after i.v. administration were best described by the biexponential equations C = 34.77.e-2.655.t+ 39.03.e-0.241.t for sulphamethoxazole and C = 3.29.e-3.878.t+ 0.83.e-0.306.t for trimethoprim. Mean biological half-lives of the drugs were 2.89 ± 0.11 and 2.38 ± 0.33 h, respectively. The distribution volumes (Varea) were 0.475 ± 0.026 l/kg (sulphamethoxazole) and 3.89 ± 0.61 I/kg (trimethoprirn). Orally administered sulphamethoxazole and trimethoprim were rapidly absorbed. The maximum serum concentrations were reached 0.5-1 h after administration. The bioavailability was 8 1% for sulphamethoxazole and 41% for trimethoprim.  相似文献   

10.
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   

11.
Considering the already known pharmacological features of cefotaxime, a study with two approaches of pharmacokinetics and clinical efficacy in septicaemic dogs was carried out. Pharmacokinetic variables were defined for doses of 10 mg/kg, and 20 mg/kg, utilising a quantitative bacteriological analysis. Values for half-life (T1/2 beta) at 10 mg/kg were 0.8, 1.48 and 1.52 h for the i.v., s.c. and i.m. routes, respectively. Corresponding values for the 20 mg/kg dose for the same routes were 0.8, 1.49 and 1.53 h, respectively. Relatively fast clearance (ranging from 0.58 to 0.64 L/kg/h) allowed a maximum dose interval of 12 h. The above-stated doses of cefotaxime were administered i.v. to 40 cases of septicaemia, clinically divided into 20 moderately severe cases treated with 10 mg/kg i.v., of cefotaxime bid, and 20 severe ones, treated with 20 mg/kg i.v. of cefotaxime bid. Injections continued until a previously defined criterion of 'clinically recovered' was obtained. Thereafter, a follow-up treatment was established using the same dose and dose-interval but through the s.c. route. Due to the apparent volumes of distribution obtained (ranging from 0.48 to 0.51 L/kg), considering the overall clinical efficacy obtained (90% for the 10 mg/kg dose and 75% for the 20 mg/kg dose), and due to the rapid improvement observed after a few doses of the drug (1.8 to 2.5 doses to 'clinical improvement'), it is safe to postulate such doses of cefotaxime as excellent choices for the treatment of septicaemia in dogs.  相似文献   

12.
The effects of intravenous (i.v.), intramuscular (i.m.) and oral administration of lysine-acetylsalicylate (Lys-ASA) on gastro-intestinal motility were investigated in sheep using electromyography. A dose of 20 mg/kg Lys-ASA intravenously reduced the frequency of reticular contractions for 86 ± 18 min, produced abomasal hypomotility and caused a disruption of the cyclical pattern of intestinal motility for at least 120 min. The frequency of reticular contractions measured from 20 to 30 min after Lys-ASA administration was negatively correlated (ß= 0.97; PΔ0.01) to the log of the dose used for doses varying from 10 to 40 mg/kg. Similar effects were observed with intramuscular and oral dose rates of 40 and 80 mg/kg, respectively. Previous i.v. administration of phentolamine (0.1 mg/kg) or tolazoline (2 mg/kg) abolished the effects of Lys-ASA (20 mg/kg) administered intravenously on both reticular contractions and abomaso-intestinal motility.
It was concluded that Lys-ASA administered at therapeutic doses in sheep produced gastro-intestinal motor disturbances and that α-and α2-adrenergic antagonists are able to block them.  相似文献   

13.
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   

14.
Pharmacokinetics of tobramycin in the camel   总被引：1，自引：0，他引：1  
A/Hadi, A.A., Wasfi, I.A., Gadir, F.A., Amiri, M.H., Bashir, A.K. Baggot, J.D. Pharmacokinetics of tobramycin in the camel. J. vet. Pharmacol. Therap. 17 . 48–51.
The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m. administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 ± 21 min and the mean residence time was 254 ± 26 min. The apparent volume of distribution (area method) was 245 ± 21 ml/kg. while volume of the central compartment of the two-compartment pharmaco-kinetic model was 110 ± 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 ± 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 ± o.59 g/ml at 20–30 min; the absorption half-life was 3.9 ± 0.9 min. The systemic availability of tobramycin was 90.7 ± 14.4%. The apparent half-life was 201 ±40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 g/ml with peak serum concentration approaching, but not exceeding, 10 g/ml.  相似文献   

15.
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   

16.
Oxytetracycline (OTC) pharmacokinetics were studied in the red pacu ( Colossoma brachypomum ) following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 5 mg/kg body weight. OTC plasma concentrations were determined by high-performance-liquid-chromatography (HPLC). A non-compartmental model was used to describe plasma drug disposition after OTC administration. Following i.m. administration, the elimination half-life ( t ½) was 62.65 ± 1.25 h and the bioavailability was 49.80 ± 0.01%. After i.v. administration the t ½ was 50.97 ± 2.99 h, the V d was 534.11 ± 38.58 mL/kg, and CI b was 0.121 ± 0.003 mL/min.kg. The 5 mg/kg i.v. dose used in this experiment resulted in up to 48 h plasma concentrations of OTC above the reported MIC values for some strains of fish pathogens such as Aeromonas hydrophila , A. liquefaciens , A. salmonicida , Cytophaga columnaris , Edwardsiella ictaluri , Vibrio anguillarium , V. ordalii , V. salmonicida and Yeersinia ruckeri . These MIC values are below the susceptible range (4 μg/mL) listed by the National Committee for Clinical Laboratory Standards (NCCLS) as determined by the NCCLS susceptibility interpretive criteria.  相似文献   

17.
Plasma concentration time curves following intravenous (i.v.) administration of 1.5 mg/kg of ranitidine, 0.2 mg/kg, 0.4 mg/kg and 0.8 mg/kg of omeprazole, respectively, were analysed in six llamas. Plasma profiles after i.v. administration of both drugs showed plasma concentrations declining in a biexponential manner with a rapid distribution phase. Pharmacokinetics parameters after ranitidine administration to six llamas showed a mean elimination half-life of 1.53 +/- 0.26 h. The mean volume of distribution (Vdss) in llamas was 1.77 +/- 0.31 L/kg, and mean body clearance in llamas was 0.778 +/- 0.109 L/kg/h. Ranitidine produced only a small transitory (<1 h) decline in acid production when administered i.v. at a dose of 1.5 mg/kg. Omeprazole showed dose-dependent nonlinear pharmacokinetics. The mean half-life of 0.2 mg/kg i.v. omeprazole was shorter than that of 0.4 and 0.8 mg/kg i.v. omeprazole, i.e. 0.61, 0.72 and 1.07 h, respectively. The area under the curve (AUC) and mean residence time (MRT) increased with increasing dose, while clearance decreased as dose increased. The decline in acid production following 0.2 mg/kg i.v. omeprazole was highly variable and did not produce a clinically useful suppression of third compartment acid production. In contrast, both 0.4 mg/kg and 0.8 mg/kg omeprazole i.v. administration significantly reduced third compartment acid production. The reduction in acid production following 0.8 mg/kg omeprazole was not significantly greater than the reduction observed following 0.4 mg/kg dosage. Misoprostol (10 microg/kg) was administered i.v. in an absolute alcohol solution. Two animals collapsed following drug administration. While the side-effects could have been produced by either misoprostol or the alcohol vehicle, the clinical changes were more consistent with an adverse drug reaction. Unfortunately, the limitation of UV detection did not provide the sensitivity needed to quantify the amount of misoprostol in llama plasma, and the pharmacokinetics could not be evaluated.  相似文献   

18.
Pharmacokinetics of valacyclovir in the adult horse   总被引：1，自引：0，他引：1  
Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7–11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7–34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance liquid chromatography. Following the administration of 5 g VCV, the mean observed maximum serum ACV concentration ( C max) was 1.45 ± 0.38 (SD) μg/mL, at 0.74 ± 0.43 h. At a dose of 15 g VCV, the mean C max was 5.26 ± 2.82 μg/mL, at 1 ± 0.27 h. The mean bioavailability of ACV from oral VCV was 60 ± 12% after 5 g of VCV and 48 ± 12% after 15 g VCV, and did not differ significantly between dose rates ( P  > 0.05). Superposition suggested that a loading dose of 27 mg/kg VCV every 8 h for 2 days, followed by a maintenance dose of 18 mg/kg every 12 h, will maintain effective serum ACV concentrations.  相似文献   

19.
To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.  相似文献   

20.
Twelve mixed-breed swine (26.5-42.5 kg) received three daily intramuscular (i.m.) doses of 14C-ceftiofur hydrochloride. Three males and three females, received 6.76 ± 0.83 mg of 14C-ceftiofur free acid equivalents (CFAE)/kg body weight (b.w.)/day, while the other group received 4.41 ± 0.97 mg-CFAE/kg b.w./day. The swine were slaughtered 12 h following the last dose. Total dose accountability for the 6.76 mg dose was 91.44 ± 16.11% (72.51% in urine; 12.63% in faeces). For the 4.41 mg dose, accountability was 100.35 ± 20.45% (82.48% in urine; 12.85% in faeces). Within the tissues used for residue monitoring, the highest concentrations were observed in the kidneys (10.68 and 6.33 μg-CFAE/g for the 6.76 and 4.41 mg doses, respectively), followed by the injection sites, lungs, liver and muscle. In a separate study, twelve mixbreed swine (23.1-39.7 kg) received 14C-ceftiofur hydrochloride at 3.08 mg-CFAE/kg b.w. once daily for 3 days. Two males and two females were slaughtered at either 12, 72 or 120 h after the last dose. Total dose accountability for the 3.08 mg dose was > 83% (> 68% in urine; > 13% in faeces). In swine slaughtered 12 h after the last dose, residue concentrations closest to the safe concentrations were observed in the kidneys (3.62 μg-CFAE/ g), followed by the injection sites, lungs, liver and muscle.  相似文献   

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