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1.
A 20% solution of apramycin was administered intravenously (j.v.) and intramuscularly (i.m.) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i.v. to lactating goats with normal udders. The i.v. disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26–1.45 L/kg. The absorption rate of the drug from the i.m. injection site was rapid, the i.m. bioavailability was 60–70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%). Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUC milk/ AUC serum was < 0.32. Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk C max values were more than tenfold greater than the C max in normal milk. On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.  相似文献   

2.
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   

3.
The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.  相似文献   

4.
Twelve (12) lactating dairy goats (46–71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC 0–∞ was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC 0–∞ was dose-proportional from 1.1–2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by C max, and serum concentrations were dose-proportional after the multiple dosing regimen.  相似文献   

5.
The pharmacokinetics and pharmacological efficacy of orally (p.o.) administered acepromazine were studied and compared with the intravenous (i.v.) route of administration in a cross-over study using six horses. The oral kinetics of acepromazine can be described by a two-compartment open model with first-order absorption. The drug was rapidly absorbed after p.o. administration with a half-life of 0.84 h, t max of 0.4 h and C max of 59 ng/ml. The elimination was slower after p.o. administration (half-life 6.04 h) than after i.v. injection (half-life 2.6 h). The bioavailability of the orally administered drug formulation was 55.1%. After p.o. administration of 0.5 mg/kg acepromazine, the parameters of the sedative effect were similar to those obtained after i.v. injection of 0.1 mg/kg. The effect of the drug on blood cell count and haemoglobin content was similar after both p.o. administration and injection, while the effects on the parameters of penile prolapse and on the mean arterial blood pressure were less pronounced after p.o. administration than after injection. After p.o. administration, no significant effects on haematoerit-level as well as on the heart and respiratory rates were observed, while these parameters were significantly affected after injection. It is concluded that the high initial plasma level of the drug after i.v. injection may play a role in producing adverse effects of acepromazine.  相似文献   

6.
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   

7.
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   

8.
Concentrations of chloramphenicol (C M) were determined, by microbiological assay, in the milk and blood serum of 17 culled dairy cows after intramammary infusion of an approved parenteral CM product (Gloveticol) and in the milk of 16 lactating cows after treatment with two approved CM products for intramammary infusion, at dosages ranging from 1 to 30 g/cow. C M was quickly absorbed from the udder into the blood circulation; the doses of 12.5 and 25 g/cow were almost completely absorbed within 20 hours. Absorption half-life (t1/2ab) from fully functioning quarters was 57+/-18 minutes, and the t1/2ab from partially functioning quarters was 125+/-37 minutes. Mean peak serum C M concentrations were 6.1, 16.2, and 37.4 microg/ml after the cows had been infused with 5, 12.5, and 25 g, respectively. These values were considerably higher than the corresponding peak serum C M concentrations reported following intramuscular injection of equivalent doses of the drug. C M residues were not detectible microbiologically in milk from treated quarters 20 hours after treatment with 5 g or 6.25 g, and 36 hours after treatment with 15 g. Drug concentrations in the milk from the non-treated quarters were approximately 70 per cent of the corresponding serum drug levels. Serum CM concentrations of potential therapeutic value in the treatment of gram-negative bacterial infections, i.e. > 5 microg/ml, were maintained for 8 hours after cows had been infused with 12.5 g, and for 12 hours after infusion with 25 g. The implications of the improved systemic availability of C M infused by the intramammary route over the intramuscular route are discussed in terms of potential therapeutic efficacy, local irritation, and duration of drug residues.  相似文献   

9.
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   

10.
The aim of this work was to determine the pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) ceftazidime administered to lactating (LTG; n=6) and non-lactating (NLTG; n=6) healthy Creole goats in 2 trials (T1 and T2). During T1 and T2, goats randomly received a single dose of i.m. or i.v. ceftazidime (10 mg/kg). Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P < 0.05) in the constants (lamda(z), T1 vs. T2 [i.v.] 0.5 +/- 0.1 vs. 0.3 +/- 0.1/h; T1 vs. T2 [i.m.] 0.5 +/- 0.2 vs. 0.3 +/- 0.1/h) and in the mean times (t(1/2), T1 vs. T2 [i.v.] 1.6 +/- 0.3 vs. 2.3 +/- 0.6 h; T1 vs. T2 [i.m.] 1.6 +/- 0.7 vs. 2.6 +/- 0.9 h) of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 +/- 17.8 and 96.0 +/- 18.0%, respectively. Ceftazidime concentration in milk at 2 h was: i.v. = 1.9 +/- 0.2 and i.m. = 2.4 +/- 0.5 microg/ml; the penetration in milk was i.v. = 18.3 +/- 13.5 and im = 14.3 +/- 10.6%. Ninety-six hours after i.v. and i.m. administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the i.m. route.  相似文献   

11.
Values for pharmacokinetic variables are usually obtained in healthy animals, whereas drugs are frequently administered to diseased animals. This study investigated cefquinome pharmacokinetics in healthy goats and goats with experimentally induced mastitis. Five adult lactating goats received 75 mg of cefquinome intramammary infusion using a commercially available product into one udder half in healthy goats and goats with clinical mastitis that was induced by intracisternal infusion of 100 cfu of Staphylococcus aureus ATCC 29213 suspended in 5 ml of sterile culture broth. Cefquinome concentrations were determined in plasma and skimmed milk samples using high‐performance liquid chromatography (HPLC). Pharmacodynamics was investigated using the California Mastitis Test and pH of milk. Experimentally induced mastitis significantly increased the California Mastitis Test score and pH, and decreased the maximal cefquinome concentration and shortened the half‐life in milk when compared to healthy goats. In conclusion, mastitis facilitated the absorption of cefquinome from the mammary gland of lactating goats and induced marked changes in milk pH, emphasizing the importance of performing pharmacokinetic studies of antimicrobial agents in infected animals.  相似文献   

12.
The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (1 5 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h-1 and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (Vd(area)) of approximately 0.9 l/kg. The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k12 > k21). Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.  相似文献   

13.
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 F 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 F 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 F and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.  相似文献   

14.
The transplacental exchange of moxidectin after maternal or fetal intravenous (i.v.) administration was studied using the chronically catheterized fetal sheep model. Nine pregnant Suffolk Down sheep of 65.7 ± 5.9 kg body weight (bw) were surgically prepared to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. The ewes were randomly assigned to two experimental groups. In group 1 (maternal injection) five ewes were treated with an i.v. bolus of 0.2 mg of moxidectin/kg bw. In group 2, (fetal injection) an i.v. bolus of 1 mg of moxidectin was administered to the four fetuses by femoral vein catheters. Maternal and fetal blood and amniotic fluid samples were taken before and after moxidectin administration for a 144 h post-treatment period. Samples were analyzed by liquid chromatography. A noncompartmental pharmacokinetic analysis was performed and statistical differences were determined by mean of parametric and nonparametric statistical tests. Pharmacokinetic differences observed in maternal variables were shorter elimination half-life and mean residence time compared with values previously reported for ivermectin. Drug diffusion from maternal to fetal circulation ( AUC 0– t  = 232.6 ± 72.5 ng·h/mL) was statistically not different ( P =  0.09) compared with fetal to maternal diffusion ( AUC 0– t = 158.0 ± 21.6 ng·h/mL). Fetuses showed significantly ( P  =   0.008) lower drug body clearance values compared with those observed in the maternal side. Considering the observed transplacental passages between materno-fetal or feto-maternal circulations, we conclude that the placental barrier is not effective in preventing the moxidectin diffusion between mother and fetus.  相似文献   

15.
A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t 1/2, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t1/2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t 1/2's 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB2 production, with mean kmax values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.  相似文献   

16.
The pharmacokinetic properties of ceftriaxone were investigated in 10 goats following a single intravenous (i.v.) and intramuscular (i.m.) administration of 20 mg kg(-1) body weight. After i.v. injection, ceftriaxone serum concentration-time curves were characteristic of a two-compartment open model. The distribution and elimination half-lives (t(1/2alpha), t(1/2beta)) were 0.12 and 1.44 h respectively. Following i.m. injection, peak serum concentration (C(max)) of 23.6 microg ml(-1) was attained at 0.70 h. The absorption and elimination half-lives (t(1/2ab), t(1/2el)) were 0.138 and 1.65 h respectively. The systemic bioavailability of the i.m. administration (F %) was 85%. Following i.v. and i.m. administration, the drug was excreted in high concentrations in urine for 24 h post-administration. The drug was detected at low concentrations in milk of lactating goats. A recommended dosage of 20 mg kg(-1) injected i.m. every 12 h could be expected to provide a therapeutic serum concentration exceeding the minimal inhibitory concentrations for different susceptible pathogens.  相似文献   

17.
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   

18.
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   

19.
A pharmacokinetic study of gentamicin (5 mg/kg intravenous (i.v.)) was conducted first in cinically healthy female goats and then in the same goats after induction of fever by Escherichia coli endotoxin (0.2 μg/kg i.v.). Rectal temperature increased 1 to 1.5°C in febrile goats. Differences in the blood serum concentrations of gentamicin were not observed at any time between febrile and normal goats. The disposition kinetics of gentamicin were described by a biex-ponential expression CP= Ae-αt+ Be. Median values for the half-lives of gentamicin were 103.6 min in normal and 136.0 min in febrile goats. The apparent volume of distribution (Vd) was 263.3 ml/kg in the febrile goats which was not different from that in the normal goats (240.6 ml/kg). The volume of the central compartment (Vc) was almost identical in normal and febrile goats. The body clearance (Clβ) was observed to be 1.7 and 1.6 ml/min-kg in normal and febrile goats, respectively. Dosage regimens for gentamicin were calculated on the basis of median kinetic data.  相似文献   

20.
为研究硫酸头孢喹肟乳房注入剂对泌乳期奶牛的安全性,试验选用12头健康泌乳奶牛(6头初产、6头经产),间隔12 h对每头奶牛的4个乳区分别注入硫酸头孢喹肟乳房注入剂(规格:8 g:75 mg/支)1支,连续给药3次,比较观察给药前后奶牛的临床症状、体细胞数、日产奶量及乳区病原菌变化情况。结果显示,与给药前相比,给药期间及停药后奶牛的临床症状、体细胞数、日产奶量、乳区病原菌检测结果均无显著性差异(P>0.05)。表明硫酸头孢喹肟乳房注入剂对泌乳期奶牛是安全的。  相似文献   

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