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1.
Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C max), and areas under the concentration curve ( AUC0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0– of 457 ± 66 ng±day/mL (± SD) and a mean C max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC 0– of 475 ± 82 ng-day/mL and a mean C max of 33.1 ± 9.0 ng/mL Absorption constants ( k a) determined by modelling were 0.542 ± 0.336 day-1after sc administration and 0.710 ± 0.357 day-1after i.m. administration. The 90% confidence limits on the difference between mean AUC 0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.  相似文献   

2.
Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, 'peak' and 'trough' samples were taken throughout the 28-day dosing period. Plasma was assayed for total (free and protein-bound) clomipramine and desmethylclomipramine, using gas-chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration ( t max) of clomipramine was 0.75–3.1 h, maximum plasma concentration ( C max) was 16–310 ng/mL and elimination half-life ( t 1/2el) was 1.2–16 h; t max of desmethylclomipramine was 1.4–8.8 h, C max was 21–134 ng/mL and t 1/2el was 1.2–2.3 h. Following multiple dosing, there was a numeric increase in these parameters; t max of clomipramine was 3–8 h, C max was 43–222 ng/mL and t 1/2el was 1.2–16 h; t max of desmethylclomipramine was 1.4–8.8 h, C max was 21–134 ng/mL and t 1/2el was 1.2–2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.  相似文献   

3.
Plasma pharmacokinetics and urine concentrations of meropenem in ewes   总被引：1，自引：0，他引：1  
The pharmacokinetics of meropenem was studied in five ewes after single i.v. and i.m. dose of 20 mg/kg bw. Meropenem concentrations in plasma and urine were determined using microbiological assay method. A two-compartment open model was best described the decrease of meropenem concentration in plasma after an i.v. injection. The drug was rapidly eliminated with a half-life of elimination ( t 1/2 β ) of 0.39 ± 0.30 h. Meropenem showed a small steady-state volume of distribution [ V d(ss)] 0.055 ± 0.09 L/kg. Following i.m. injection, meropenem was rapidly absorbed with a t 1/2ab of 0.25 ± 0.04 h. The peak plasma concentration ( C max) was 48.79 ± 8.83  μ g/mL was attained after 0.57 ± 0.13 h ( t max). The elimination half-life ( t 1/2el) of meropenem was 0.71 ± 0.12 h and the mean residence time ( MRT ) was 1.38 ± 0.26 h. The systemic bioavailability (F) after i.m. injection was 112.67 ± 10.13%. In vitro protein-binding percentage of meropenem in ewe's plasma was 42.80%. The mean urinary recoveries of meropenem over 24 h were 83% and 91% of the administered dose after i.v. and i.m. injections respectively. Thus, meropenem is likely to be efficacious in the eradication of many urinary tract pathogens in sheep.  相似文献   

4.
Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t 1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t 1/2el), mean residence time, and maximum plasma concentration ( C max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.  相似文献   

5.
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   

6.
The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life ( t 1/2k) of 9.2 h, area under the time–concentration curve ( AUC ) of 12.4 ng·h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution ( V d) was 1616.0 mL/kg and plasma clearance ( Cl ) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrations also declined mono-exponentially with a median elimination half-life ( t 1/2k) of 12.9 h, a Cl of 94.0 mL/h/kg and V d of 1574.7 mL/kg. Following the last p.o. administration the baseline plasma concentration was 537.5 ± 268.4 and increased to 1302.6 ± 925.0 pg/mL at 0.25 h, and declined to 18.9 ± 7.4 pg/mL at 96 h. CLB was still quantifiable in urine at 288 h following the last administration (210.0 ± 110 pg/mL). The difference between plasma and urinary concentrations of CLB was 100-fold irrespective of the route of administration. This 100-fold urine/plasma difference should be considered when the presence of CLB in urine is reported by equine forensic laboratories.  相似文献   

7.
This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C max, 5.5 ± 2.6 μg/mL; T max, 0.75 ± 0.27 h; AUC 0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.  相似文献   

8.
The objective of this study was to determine the kinetic parameters of a new formulation that contained 2.25% ivermectin combined with 1.25% abamectin in bovine plasma. The results for 2.25% ivermectin: C max (37.11 ng/mL ± 7.42), T max (16 days ± 5.29), T 1/2 (44.62 days ± 53.89), AUC (928.2 ng·day/mL ± 153.83) and MRT (36.73 days ± 33.64), and for 1.25% abamectin: C max (28.70 ng/mL ± 9.54), T max (14 days ± 4.04), T 1/2 (15.40 days ± 11.43), AUC (618.05 ng·day/mL ± 80.27) and MRT (20.79 days ± 8.43) suggest that this combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give this pharmaceutical formula a longer activity time than two of the commercial products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15% ivermectin.  相似文献   

9.
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   

10.
The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high-pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determined in vitro . Following i.v. administration, orbifloxacin had a terminal half-life ( t 1/2) of 5.08 h and a volume of distribution (Vd(ss)) of 1.58 L/kg. Following oral administration, the average maximum plasma concentration ( C max) was 1.25  μ g/mL with a t 1/2 of 3.42 h. Systemic bioavailability was 68.35%. Plasma protein binding was 20.64%. The octanol:water partition coefficient (pH 7.4) was 0.2 ± 0.11. No adverse reactions were noted during this study. Dosage regimens were determined from the pharmacokinetic–pharmacodynamic parameters established for fluoroquinolone antibiotics. For susceptible bacteria, an oral dose of approximately 5 mg/kg once daily will produce plasma concentrations within the suggested range. This dose is suggested for further studies on the clinical efficacy of orbifloxacin for treatment of susceptible bacterial infections in the horse.  相似文献   

11.
The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox® Oral Suspension 2.5%) and doxycycline (Ronaxan® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t max). In saliva and tear fluid, mean C max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.  相似文献   

12.
The intramuscular (i.m.), oral (p.o.), and bath immersion disposition of enrofloxacin were evaluated following administration to a cultured population of red pacu. The half-life for enrofloxacin following i.m. administration was 28.9 h, considerably longer than values calculated for other animals such as dogs, birds, rabbits, and tortoises. The 4 h maximum concentration ( C max) of 1.64 μg/mL following a single 5.0 mg/kg dosing easily exceeds the in vitro minimum inhibitory concentration (MIC) for 20 bacterial organisms known to infect fish. At 48 h post i.m. administration, the mean plasma enrofloxacin concentration was well above the MIC for most gram-negative fish pathogens. The gavage method of oral enrofloxacin administration produced a C max of 0.94 μg/mL at 6–8 h. This C max was well above the reported in vitro MIC. A bath immersion concentration of 2.5 mg/L for 5 h was used in this study. The C max of 0.17 μg/mL was noted on the 2 hour post-treatment plasma sample. Plasma concentrations of enrofloxacin exceeded published in vitro MIC's for most fish bacterial pathogens 72 h after treatment was concluded. Ciprofloxacin, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the red pacu using p.o., i.m., and bath immersion administration. The i.m. route is the most predictable and results in the highest plasma concentrations of the drug.  相似文献   

13.
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   

14.
The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V dss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C lB) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t ½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K ab = 26 ± 18 h-1) and short ( t ½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.  相似文献   

15.
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   

16.
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   

17.
Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t ½β) of pentoxifylline was 1.44 h and volume of distribution ( V darea) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.  相似文献   

18.
Bioavailability and pharmacokinetics of metoclopramide in cattle   总被引：1，自引：0，他引：1  
The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (± SD) oral and abomasal bioavailabilitles were 51.3 ± 30.7% and 76.2 ± 15.5%, respectively. The mean value for clearance ( C1 ) was 20.1 ± 5.9 ml/min and the volume of distribution ( V d) was 0.51 ± 0.19 1/kg. Additionalpharmacokmetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t 1/2α harmonic mean of 24.2 min and a range of 11.2–72.4 min, a t 1/2β harmonic mean of 53.1 min and a range of 31.1–134.1 min, a Cl of 42.2 ± 8.7 ml/min, and a V d of 2.1 ± 0.8 1/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration ( MCP ss) of 8.8 ± 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 ± 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations ( PRL ss) did not rise significantly above 23.3 ± 6.9 ng/ml, even when MCP ss reached a concentration of 518.5 ±151.2 ng/ml. The short half-life, moderate V d, low minimum pharmacologically effective concentration, and rapid C1 found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.  相似文献   

19.
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) F2α. 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   

20.
Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasma concentrations of tepoxalin were undetectable, whereas in fasting animals they were close to the limit of quantification of the method. No differences between the fasting/fed groups in RWJ-20142 plasma concentrations were shown. Tepoxalin showed a strong and long-lasting ex vivo inhibitory activity against cyclooxygenase (COX)-1, mainly due to its main metabolite RWJ-20142. Tepoxalin and RWJ-20142 do not seem to possess either COX-2 or 5-lipoxygenase inhibitory activity in the horse. These features suggest that the drug is a selective COX-1 inhibitor in horses, with no significant anti-inflammatory activity. Thus, its long term use in equine practice could be of concern.  相似文献   

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