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1.
The disposition of five therapeutic antimicrobial agents was studied in llamas ( Lama glama ) following intravenous bolus administration. Six llamas were each given ampicillin, tobramycin, trimethoprim, sulfamethoxazole, enrofloxacin and ceftiofur at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg, 15 mg/kg, 5 mg/kg, and 2.2 mg/kg of body weight, respectively, with a wash out period of at least 3 days between treatments. Plasma concentrations of these antimicrobial agents over 12 h following i.v. bolus dosing were determined by reverse phase HPLC. Disposition of the five antimicrobial agents was described by a two compartment open model with elimination from the central compartment, and also by non-compartmental methods. From compartmental analysis, the elimination rate constant, half-life, and apparent volume of distribution in the central compartment were determined. Statistical moment theory was used to determine noncompartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at stead state. Based on the disposition parameters determined, and stated assumptions of likely effective minimum inhibitory concentrations (MIC) a dose and dosing interval for each of five antimicrobial agents were suggested as 6 mg/kg every 12 h for ampicillin; 4 mg/kg once a day or 0.75 mg/kg every 8 h for tobramycin; 3.0 mg/kg/15 mg/kg every 12 h for trimethoprim/sulfamethoxazole; 5 mg/kg every 12 h for enrofloxacin; and 2.2 mg/kg every 12 h for ceftiofur sodium for llamas. Steady-state peak and trough plasma concentrations were also predicted for the drugs in this study for llamas.  相似文献   

2.
The disposition kinetics and residue levels of phenylbutazone (8 mg/kg) were studied in rabbit. The result suggested that distribution of phenylbutazone can be described by a two open compartment. Elimination half-time is short (2 h) and estimation of residue levels in muscle, liver and kidney did not differ significantly before and after bleeding. These results suggest that biopsy can be used to determine the phenylbutazone concentration in tissues of larger species. Moreover, using a pharmacokinetic approach based on drug concentrations in plasma, it appears that the mean resting quantity in the peripheral compartment was very close to the experimental data for the muscle.  相似文献   

3.
Pharmacokinetic parameters for the beta 2-adrenergic agonist, cimaterol (CIM), were determined in growing Holstein steers. Compartmental analysis was used after measurement of CIM in body fluids by affinity chromatography and HPLC using UV detection. Recoveries from spiked plasma and urine standards were 70 +/- 1.2% and 68 +/- 1.1%, respectively. The minimum detection level in plasma was 1 ng/mL and the average CV was 5.1% for concentrations that ranged from 1 to 30 ng/mL. Four steers (276 +/- 24 kg) received 15 mg of CIM by bolus intravenous injection. Plasma CIM levels declined in a biphasic manner with half-lives of 2.5 min for the distribution phase and 54 min for the elimination phase. A two-compartment open model was used to describe the disappearance of CIM and the following pharmacokinetic parameters were obtained: central compartment volume (Vc) = .76 L/kg, apparent volume of distribution (Vd) = 4.1 L/kg, and transfer rate constants from the central to peripheral compartment (k12) = .177/min, from the peripheral to central compartment (k21) = .054/min and elimination from the central compartment (kel) = .074/min. After 8 h, total urinary CIM accounted for only 18.3% of the administered dose. Results suggest that circulating concentrations of CIM in growing steers are influenced by its accumulation in an unidentified peripheral pool and its conversion into unknown metabolite(s) before elimination.  相似文献   

4.
Neomycin sulfate was administered to calves by the intravenous and intramuscular routes. Serum drug levels were determined and the intravenous pharmacokinetic parameters derived using the Gauss-Newton nonlinear fitting algorithm and the two compartment open model. The kinetic parameters determined were as follows: zero time intercept, serum drug level 68.045 +/- 15.894 micrograms/mL, alpha slope intercept 37.666 +/- 13.874 micrograms/mL and beta slope intercept 30.379 +/- 12.638 micrograms/mL; equilibration rate (pool I and II) 0.081 +/- 9.064 min-1; elimination rate 0.004 +/- 0.001 min-1; half-time alpha 14.774 +/- 11.236 min, half-time beta 166.596 +/- 47.576 min; first order elimination constant 0.009 +/- 0.002 min+; transfer rate constants, central to peripheral, 0.032 +/- 0.026 min+ and peripheral to central 0.045 +/- 0.037 min-1; volume of central compartment 0.186 +/- 0.047 L/kg; volume of distribution 0.388 +/- 0.130 L/kg; body clearance 0.002 +/- 0.001 L/kg/min.  相似文献   

5.
A proprietary combination product containing sulphadoxine and trimethoprim was administered to horses by intravenous injection. Protein-binding of sulphadoxine was dependent on the concentration in plasma and decreased from 72% at 50 μg/ml to 14% at 450 μg/ml. Sulphadoxine is eliminated from plasma in accordance with a three compartment open model. The elimination half-life was on average 14 h while the volume of distribution was found to be 0.39 1/kg. Trimethoprim was eliminated from plasma in accordance with a two compartment open model. The elimination half-life was on an average 3 h. Experiments in which trimethoprim was administered alone showed that the elimination half-life was not dependent on the simultaneous administration of sulphadoxine. About 50% of trimethoprim was bound to plasma proteins, but in contrast to sulphadoxine there was no dependence between plasma concentration and protein binding. The protein binding of trimethoprim was independent of the presence of sulphadoxine and vice versa. Experiments with 14C-labelled trimethoprim showed that it was excreted in almost equal amounts in urine and faeces. 97% of the administered dose was recovered in urine and faeces during the course of the first 4 days after administration.  相似文献   

6.
The pharmacokinetic properties of flumequine and its metabolite 7-hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable®. The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (Vdss) (0.52 ± 0.24 L/kg) and high value of volume of distribution (Vdλ3) (5.05 ± 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 ± 1.15 μg/mL) was obtained rapidly, i.e. 1.39 ± 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 ± 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. admini-stration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.  相似文献   

7.
Ketamine hydrochloride was administered intravenously to unpremedicated and xylazine-treated calves. The plasma concentrations of ketamine and norketamine were measured at several time intervals after drug administration and the data were fitted to a two-compartment open model. In unpremedicated female calves the distribution and elimination half-lives averaged 6.9 and 60.5 min, respectively. The volume of the central compartment was 1.21 1/kg and the peripheral compartment was 4.04 1/kg. Total body clearance of ketamine averaged 40.4 ml/ min/kg. Premedication with xylazine, whilst not affecting the half-lives signifi-candy, reduced volumes of distribution and the clearance rate of the drug by approximately 50%. The results for the male calves which were premedicated were intermediate between the two groups of female calves.  相似文献   

8.
The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration‐time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half‐life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration‐anticonvulsant relationship preclinically in dogs.  相似文献   

9.
Summary

The disposition and urinary excretion of ciprofloxacin (CIP) following intravenous (IV) or intramuscular (IM) administration of 7.5 mg/kg body weight in sheep (n = 5) was studied. The intravenous plasma concentration curve was best described pharmacokinetically by a two‐compartment open model, while the intramuscular administration data fitted better to a one‐compartment open model. Mean elimination half‐lives after IV and IM administration were 72 and 184 minutes, respectively. The absorption of intramuscularly administered CIP in sheep was fast: maximal plasma concentration (Cmax) was reached quickly (tmax 31.93 min) and attained values of 0.69 ± 0.27 mg/l. The bioavailability was 49%. The urinary data showed a significant decrease in the elimination rate constant of CIP when CIP was administered intramuscularly. The other parameters calculated did not display differences between the two routes of administration. The results obtained suggest that when CIP was administered by the IM route in the assayed dose, it was able to maintain serum concentrations above the MIC of most common pathogens over an 8‐hour period.  相似文献   

10.
Pharmacokinetics of ciprofloxacin in ponies   总被引：8，自引：0，他引：8  
The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 15 7.8 9 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 ± 3.99 mL/min/kg. Volume of distribution at steady-state was 3.45 ± 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram-negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 ± 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aqueous humour.  相似文献   

11.
Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high-performance liquid chromatography method. A three-compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 ± 196 ml/kg; body clearance was 3.5 ± 0.8 ml/minkg and the half-life, based on the slope of the terminal portion of the curve, was 196 ± 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half-time of 26.5 ± 2.87 sec was calculated. At the time of awakening (36.6 ± 6.36 min) 24.1 ± 6.3% of the dose was located in the central compartment, 12.6 ± 8.2 was in the shallow peripheral compartment, 38.8 ± 14.1 was in the deep peripheral compartment and 24.6 ± 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination-rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.  相似文献   

12.
Benzylpenicillin pharmacokinetics were compared in the dromedary Camelus dromedarius (n = 5) and in sheep (n = 5) after administration of a single intravenous injection of benzylpenicillin. The data were described by an open three-compartment model with elimination from the central compartment. Body clearance (Clb) was 4.87 +/- 0.63 ml/min/kg in the dromedary and 9.17 +/- 1.39 ml/min/kg in sheep, the steady-state volumes of distribution (Vss) were 0.151 +/- 0.023 l/kg and 0.165 +/- 0.038 l/kg and the mean residence times (MRT) 27.34 +/- 1.38 min and 14.95 +/- 4.16 min in the dromedary and in sheep, respectively. It was concluded that benzylpenicillin elimination occurs more slowly in the dromedary than in sheep and that use of the same dosage regimen for the two ruminant species may lead to significant differences in plasma concentrations and therapeutic efficacy.  相似文献   

13.
Phenylbutazone was administered intravenously and intramuscularly at a dosage rate of 4.4 mg/kg to a group of 6 female camels in a two-period crossover study. After intravenous (i.v.) administration, disposition was characterised by a two-compartment open model, with a low volume of distribution (0.174 l.kg–1), and distribution and elimination half-lives of 0.43 and 12.51 h, respectively. After intramuscular (i.m.) dosing absorption was relatively rapid with absorption half-time and time of maximal concentration values of 1.14 and 3.95 h, respectively. Plateau concentrations of phenylbutazone in plasma were obtained between 2 and 12 h and mean bioavailability was 97%, although this was subject to wide inter-animal differences. Plasma concentrations of the phenylbutazone metabolite, oxyphenbutazone, were low after iv dosing and generally undetectable after im administration, indicating that it is unlikely to contribute significantly to the pharmacological effects produced by phenylbutazone administration. An indication was obtained that phenylbutazone inhibited the ex vivo synthesis of serum thromboxane B2 (TxB2) for 24 h after i.v. dosing, but this finding requires confirmation.  相似文献   

14.
研究氟苯尼考磺酸盐在肉鸡体内的血药浓度及药动学特征。将12只健康三黄肉鸡,单次肌肉注射推荐治疗剂量（20mg／kg）的自制2％氟苯尼考磺酸盐。采用高效液相色谱法测定血浆药物浓度,所得数据用3P97药动软件进行分析后发现,血药浓度和时间关系符合一级吸收一室模型,选择的权重为1／C。主要药动学参数为T1／2kα：（0．28±0．04）h,T1/2Ke：（2．06±0．06）h,Cmax：（4．17±0．12）μg／mL,Tmax：（0．92±0．09）h,AUC：（16．89±0,35）μg／mL,V／F（c）：（3．52±0．13）L／kg,CL／F（s）：（1．19±0．03）L／（kg·h）,Ke：（0．34±0．01）／h,kα：（2．57±0．37）／h,A：（6．56±0．38）μg／mL。结果提示,氟苯尼考磺酸盐在肉鸡体内具有吸收迅速,分布广泛、峰浓度较高以及消除较快的动力学特征。  相似文献   

15.
The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharmacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.13h-1, t1/2 beta = 5.46h, Vdarea = 0.141 1/kg and C1B = 17.9 ml/kg/h. The hydroxylated metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbutazone (OHPBZ) were present in detectable concentrations in plasma for 72 and 24 h, respectively. After 36 h OPBZ concentrations exceeded plasma PBZ concentrations. In urine the principal metabolites were OPBZ and OHPBZ but smaller concentrations of another compound, probably gamma-hydroxyoxyphenbutazone (OHOPBZ), were also detected. The percentages of the administered dose recovered from urine were 30.7, 39.0 and 40.3 after 24, 48 and 72 h from the time of injection. Recovery of PBZ and its metabolites from urine was significantly reduced in the first 24 h after oral dosing when the horses had free access to hay, probably as a result of markedly delayed absorption, but this did not occur in animals deprived of food for a few hours before and after dosing. Determination of approximate values of urine/plasma (U/P) concentration ratios for PBZ and its metabolites relative to endogenous creatinine U/P concentration ratio suggested that PBZ was filtered in small amounts only because of the high degree of plasma protein binding and then excreted by diffusion trapping in the alkaline urine. Much higher U/P ratios were obtained for the hydroxylated derivatives, and one at least (OHPBZ) was secreted into urine.  相似文献   

17.
Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.  相似文献   

18.
The pharmacokinetics of a parenteral formulation of metoclopramide (monochloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5-mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min post-dosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two-compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half-life of 0.62 h and a volume of distribution of the central compartment of 1.34 l/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post-dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two-compartment open model with first-order absorption. The mean biological half-life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5-mg/kg dose administered by either route.  相似文献   

19.
In this study, the pharmacokinetic profile of flumequine (FMQ) was investigated in blunt snout bream (Megalobrama amblycephala) after intravascular (3 mg/kg body weight (b.w.)) and oral (50 mg/kg b.w.) administrations. The plasma samples were determinedby ultra‐performance liquid chromatography (UPLC) with fluorescence detection. After intravascular administration, plasma concentration–time curves were best described by a two‐compartment open model. The distribution half‐life (t1/2α), elimination half‐life (t1/2β), and area under the concentration–time curve (AUC) of blunt snout bream were 0.6 h, 25.0 h, and 10612.7 h·μg/L, respectively. After oral administration, a two‐compartment open model with first‐order absorption was also best fit the data of plasma. The t1/2α, t1/2β, peak concentration (Cmax), time‐to‐peak concentration (Tmax), and AUC of blunt snout bream were estimated to be 2.5 h, 19.7 h, 3946.5 μg/L, 1.4 h, and 56618.1 h. μg/L, respectively. The oral bioavailability (F) was 32.0%. The pharmacokinetics of FMQ in blunt snout bream displayed low bioavailability, rapid absorption, and rapid elimination.  相似文献   

20.
Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis. A single dose of 5 mg of aditoprim/kg of body weight was administered IV to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters. Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin. Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination half-life of 7.26 hours. In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection. The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different. The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out. The antibacterial activity of aditoprim is nearly the same as that of trimethoprim. The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.  相似文献   

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