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1.
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   

2.
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   

3.
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   

4.
Six clinically normal lactating does were administered ketoprofen (2.2 mg/kg intravenously (i. v.)). Blood and milk samples were collected prior to and for 24 h after drug administration. Drug concentrations in serum and milk were determined by high performance liquid chromatography. Pharmacokinetic parameters from each goat were combined to obtain mean estimates (mean ± SD) of half-life of elimination ( t ½β) of 0.32 ± 0.14 h, systemic clearance ( Cl ) of 0.74 ± 0.12 L/kg· h, and volume of distribution at steady state ( V ss) of 0.23 ± 0.051 L/kg. In milk, ketoprofen was unmeasurable by the method employed (level of detection 25 ng/mL) for all samples.  相似文献   

5.
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   

6.
The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean ±  SEM) for the low and high dose, respectively, were as follows:
  The elimination half-lives ( t ½β) were 3.76 ± 0.24 and 4.08 ± 0.49 h, the steady state volumes of distribution ( V dss) were 320.61 ± 38.53 and 348.84 ± 35.36 mL/kg body weight, total body clearances ( Cl T) were 88.96 ± 6.63 and 84.86 ± 4.95 mL/h/kg body weight and renal clearances ( Cl r) were 0.52 ± 0.09 and 0.62 ± 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.  相似文献   

7.
The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with ( n  = 5) or without ( n  = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) 6090 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance ( CL p) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution ( V dss) ranged from 169 to 880 mL/kg and the elimination half life ( t ½) ranged from 83 min to 209 h.   No differences in plasma concentration or kinetic parameter estimates were observed when phenylbutazone was administered before furosemide administration. BUL markedly reduces the elimination of furosemide in horses and models the potential effects that severe changes in kidney function may have on drug kinetics in horses.  相似文献   

8.
Salivary output in sheep is large enough to be considered a physiologic body fluid compartment. The hypothesis for this work was that pharmacokinetics of sulfamethazine in saliva was similar to that in plasma. A reliable technique was developed to measure parotid salivary output. Mean output of saliva was 3.18 ± 1.04 L from a single parotid gland per day with a mean flow of 2.21 ± 0.43 mL/min. Using concentrations of sulfamethazine in parotid saliva made it possible to calculate the total passage of sulfamethazine to parotid saliva, which was calculated to be 3.5% of the total dose. Pharmacokinetic variables obtained for sulfamethazine in plasma and in saliva were closely related ( AUC 1408 μg.h/mL and AUC 1484 μg.h/mL; V darea 0.434 L/kg and V d area 0.374 L/kg; t ½β 4.30 h and 3.46 h, respectively) and no substantial differences were observed. The convenience of using salivary concentrations of sulfamethazine for drug monitoring is discussed.  相似文献   

9.
The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits ( n  = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations ( MIC s) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration–time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution ( V ss) and total body clearance ( Cl ) of orbifloxacin after i.v. administration were estimated to be 1.71 ± 0.38 L/kg and 0.91 ± 0.20 L/h·kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95 ± 0.82 and 3.24 ± 1.33 mg/L at 0.67 ± 0.20 and 0.65 ± 0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67 ± 11.02% and 109.87 ± 8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC / MIC and C max/ MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations.  相似文献   

10.
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   

11.
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   

12.
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   

13.
The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives ( t ½el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution ( V ss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90–120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over ≈ 24 h.
  Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.  相似文献   

14.
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   

15.
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   

16.
The bioavailability of amprolium (APL) was measured after intravenous (i.v.) and oral (p.o.) administration to chickens. Twelve healthy chickens weighing 1.28–1.41 kg received a dose of 13 mg APL/kg intravenously, and 13 or 26 mg APL/kg orally in both a fasted and a nonfasted condition in a Latin square design. Plasma samples were taken from the subwing vein for determination of APL concentration by HPLC method. The data following intravenous and oral administration were best fitted by 2-compartment and 1-compartment models, respectively, using weighted nonlinear least squares regression. The half-life beta t ½β, volume of distribution ( V d) and total body clearance ( Cl ) after intravenous administration were 0.21 h, 0.12 L/kg and 1.32 L/h.kg, respectively. The elimination half-life ( t ½ Kel) after oral administration was 0.292–0.654 h which is 1.5–3.2 times longer than after intravenous administration, suggesting the presence of a 'flip-flop' phenomenon in chickens. The maximum plasma concentration ( C max) of 13 mg/kg APL administered orally to chickens during fasting was significantly (about four times) higher than that during nonfasting ( P < 0.05). Bioavailability during nonfasting was from 2.3 to 2.6%, and 6.4% during fasting.  相似文献   

17.
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   

18.
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   

19.
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   

20.
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   

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