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1.
This study investigated the disposition kinetics and plasma availability of ceftazidime in rabbits after single intravenous (i.v.) and intramuscular (i.m.) injections of 50 mg kg-1 b.wt. Tissue residue profiles were studied after repeated intramuscular injections of 50 mg kg-1 b. wt, twice daily for five consecutive days. A microbiological assay with Bacillus subtilis as the test organism was used to measure its concentrations in plasma and tissues. The plasma concentration-vs-time curves were best described by a two compartment open model. The decline in plasma drug concentration was biexponential with half-lives of 0.258 h for t1/2 alpha, 2.22 h for t1/2 beta, for distribution and elimination phases, respectively, following i.v. injection. After intramuscular injection of ceftazidime at the same dose, it was detected in plasma at 5 min and reached its minimum level 12 h post-injection. The peak plasma concentration (Cmax) 66.3 micrograms.ml-1 was attained at 0.779 h (Tmax). The elimination half-life (T1/2el,) was 2.12 h, the mean residence time (MRT) was 3.06 h and the systemic bioavailability was 96.6%. In vitro protein binding percent of ceftazidime in rabbit's plasma was ranged from 13.3 to 21.6%. The limit of quantification (LOQ) for the assay was 0.01 microgram.ml-1 in plasma and tissues. The tissue level concentrations were highest in the kidneys, and decreased in the following order: liver > heart > muscles and plasma. No ceftazidime residues were detected in tissues and plasma after 72 h. It is concluded that tissue kinetics is an important tool in predicting and controlling drug residues in edible tissues of food producing animal.  相似文献   

2.
This study aimed to develop one novel meloxicam (MEL) oil suspension for sustained-release and compare the pharmacokinetic characteristics of it with MEL conventional formulation in pigs after a single intramuscular administration. Six healthy pigs were used for the study by a crossover design in two periods with a withdrawal interval of 14 days. Plasma concentrations of MEL were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetic parameters were calculated by noncompartmental methods. The difference was statistically significant (p < .05) between MEL oil suspension and MEL conventional formulation in pharmacokinetic parameters of mean residence time (6.16 ± 4.04) hr versus (2.66 ± 0.55) hr, peak plasma concentration (Cmax) (0.82 ± 0.12) µg/ml versus (1.12 ± 0.22) µg/ml, time needed to reach Cmax (Tmax) (2.33 ± 0.82) hr versus (0.59 ± 0.18) hr, and terminal elimination half-life (t1/2λz) (3.74 ± 2.66) hr versus (1.55 ± 0.37) hr. The mean area under the concentration–time curve (AUC0–∝) of MEL oil suspension and MEL conventional formulation was 5.35 and 3.43 hr µg/ml, respectively, with a relative bioavailability of 155.98%. Results of the present study demonstrated that the MEL oil suspension could prolong the effective time of drugs in blood, thereby reducing the frequency of administration on a course of treatment. Therefore, the novel MEL oil suspension seems to be of great value in veterinary clinical application.  相似文献   

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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   

6.
The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.  相似文献   

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An experiment was conducted with 208 day-old male Cobb feather-sexed chicks to study tissue accumulation of Cu as an estimate of biological availability of inorganic Cu sources for chicks. Chicks were allotted randomly to dietary treatments that included an unsupplemented basal corn-soybean meal diet (11.1 mg/kg Cu, DM basis) or this basal diet supplemented with 150, 300 or 450 mg/kg Cu either as reagent-grade acetate or feed grade oxide, carbonate or sulfate. Chicks were housed in batteries and allowed ad libitum access to feed and tap water for 21 d. Liver Cu was not affected by dietary Cu from the oxide source, but it increased (P less than .001) with increasing dietary Cu from all other sources. Bone Cu was lower (P less than .05) in chicks fed 150 mg/kg Cu compared to other dietary levels of Cu but was not influenced (P greater than .10) by Cu source. Using the slope-ratio technique from regression of log liver Cu on mean daily Cu intake with Cu from acetate set at 100%, the relative biological availability values were estimated to be 88.5 and 54.3% for sulfate and carbonate, respectively, and oxide was essentially unavailable.  相似文献   

9.
Gentamicin was administered IM to 6 healthy, mature, lactating cows at a dosage of 3.5 or 5 mg/kg of body weight every 8 hours for 10 consecutive days (total, 30 doses). Endometrial biopsies were done at 72, 136 or 144, and 216 hours after the first dose was administered. On the 10th day, just before the last dose of gentamicin was administered, blood samples (designated 10th-day base-line samples) were obtained, and serial blood samples were obtained for 144 hours after the last injection was given. The cows were catheterized on the 10th day, and urine was obtained for 10 to 18 consecutive hours. Milk samples were also obtained. The cows were slaughtered at different times after the last dose was given, and samples were taken from 22 tissues and organs. Serum, milk, urine, and tissue gentamicin concentrations were determined by radioimmunoassay. Serum gentamicin concentrations were best fitted to a 2-compartment open model. The mean half-lives for absorption, distribution, and elimination were 0.16 +/- 0.14, 2.59 +/- 0.53, and 44.91 +/- 9.38 hours, respectively. Total body clearance and renal clearance were 1.65 +/- 0.69 and 1.32 +/- 0.25 ml/min/kg, respectively. The percentage of the dose excreted unchanged in the urine at 8 hours after the last dose was given was 98 +/- 15. As expected, of the tissues examined, the gentamicin concentrations in the kidney cortex and medulla were 1,500 times greater than those in serum. Renal function remained within the baseline range during the 10 days of gentamicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
1. Disposition kinetics of doxycycline (doxy) was studied in healthy chickens and chickens experimentally intoxicated with aflatoxin B1 by intravenous, oral or intramuscular (i.m.) injection, in a single dose of 15 mg/kg body weight. In addition, the tissue distribution and residual pattern of the drug were determined in healthy and intoxicated chickens. 2. The maximum serum concentrations of doxy were reached 1.97 and 2.37 h after oral, and 1.57 and 2.92 h after i.m. dosage in healthy and aflatoxic birds, respectively. 3. The volumes of distribution and total body clearances were higher in aflatoxic birds (1.75 l/kg and 14.61 ml/kg/min) than in healthy chickens (0.93 l/kg and 4.6 ml/kg/min). Data relating to intravenous injection were analysed using a two-compartment open model curve fit. 4. Lower values of systemic bioavailability were observed in intoxicated birds (30.9 and 33.9%) than healthy ones (43.7 and 57.3%) after oral and i.m. administration, respectively. 5. The highest concentration of doxy residues were present in liver, kidney and serum followed by heart and muscles. Doxy residue concentrations in edible tissues was below the EEC limit 6 d after cessation of oral or i.m. medication with 15 mg/kg body weight twice daily for 5 successive days.  相似文献   

11.
Evaluation of skeletal muscle tolerance during development of new drug formulations for i.m. use is most often based on terminal methods performed in the target species after slaughtering. The objective of this study was to evaluate the effect of muscle damage on the pharmacokinetic parameters of the drug delivered into the muscle using an alternative, noninvasive method. Phenylbutazone (PBZ) was used as the test article. Six ewes received increasing volumes of a 20% PBZ i.m. formulation, according to a cross-over design, and an i.v. bolus of the same formulation. Serial blood samples were taken, and a pharmacokinetic analysis of the plasma activity of creatine kinase and plasma PBZ concentrations was carried out. The amount of muscle damage after i.m. administration of 2, 4, or 8 mL of PBZ, calculated from the area under the curve of plasma creatine kinase across time was 36, 76, and 178 g for a 70-kg ewe. The corresponding absolute bioavailability of PBZ was 100 +/- 32%, 96 +/- 19%, and 100 +/- 17%, and the maximal PBZ concentrations were 42 +/- 3.4, 74 +/- 8.8, and 119 +/- 18.2 microg/mL. The plasma clearance of PBZ (i.v.) was 4.2 +/- 0.94 mL.kg(-1).h(-1). In conclusion, the absolute bioavailability of PBZ after i.m. administration was not altered by the increased volume of formulation administered despite the overall increase in the extent of muscle damage.  相似文献   

12.
The plasma concentrations and pharmacokinetics of rifampin disposition were determined after a single IV, IM, or oral dose of 10 mg/kg of body weight and an oral dose of 25 mg/kg. The overall elimination rate constants per minute were similar for the 10 mg/kg dose (0.0021 +/- 0.0004, IV; 0.0017 +/- 0.0002, IM; and 0.0023 +/- 0.0006, orally). The apparent bioavailability was moderate to low for IM and oral administrations (59.8% +/- 3.2% and 39.5% +/- 5.0%, respectively). The rate of absorption was most rapid for oral administration with an absorption half-life of 249.7 +/- 71.6 minutes as compared with 403.5 +/- 89.7 minutes for IM administration. However, the IM route produced longer detectable plasma concentrations (50 hours in 2 of the 4 horses). Based on bacterial sensitivity information derived for human and canine isolates, the daily oral administration of 10 mg of rifampin/kg administered in the feed represents a reasonable dose for susceptible gram-positive bacterial pathogens. Higher doses (greater than or equal to 25 mg/kg) or IV administration would be required for most gram-negative bacteria. Adverse effects of sufficient severity to limit use of the drug, especially by the oral route of administration, were not encountered under the single-dose experimental conditions used.  相似文献   

13.
The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxicillin would be required to maintain therapeutic plasma concentrations of amoxicillin, and thus, the use of this dosage form should be limited to the initiation of treatment or to intensive care situations. After intragastric administration of amoxicillin trihydrate (20 mg/kg), 5% cherry-flavored suspension, the drug was rapidly, but incompletely, absorbed and rapidly eliminated (mean half-life of the decline phase of the plasma amoxicillin concentration-time curve, 51 minutes). The mean estimated bioavailability (fractional absorption) of the administered dose was 10.4%, and the mean peak plasma amoxicillin concentration was 2.73 micrograms/ml at 1.5 hours after dosing. In one horse with clinical signs of abdominal discomfort and diarrhea, the absorption of amoxicillin from the gastrointestinal tract was delayed and the fraction absorbed was increased. It was concluded that this oral dosage form could be recommended only for the treatment of infections caused by bacteria that are highly susceptible to amoxicillin, that frequent dosing would be necessary, and that absorption may be inconsistent in horses with gastrointestinal disease.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
OBJECTIVE: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular xylazine/ketamine in llamas, and to determine if an intramuscular injection of tolazoline would shorten the anesthesia recovery time. STUDY DESIGN: Prospective randomized study. ANIMALS: Six castrated male llamas. METHODS: Each llama received a low dose (LD) (0.4 mg kg(-1) xylazine and 4 mg kg(-1) ketamine) and high dose (HD) (0.8 mg kg(-1) xylazine and 8 mg kg(-1) ketamine). Time to sedation, duration of lateral recumbency and analgesia, pulse, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood gases, and the electrocardiogram were monitored and recorded during anesthesia. Three llamas in each treatment were randomized to receive intramuscular tolazoline (2 mg kg(-1)) after 30 minutes of lateral recumbency. RESULTS: Onset of sedation, lateral recumbency, and analgesia was rapid with both treatments. The HD was able to provide at least 30 minutes of anesthesia in all six llamas. The LD provided only 30 minutes of anesthesia in two out of six llamas. Respiratory depression and hypoxemia were seen in the HD treatment during the first 10 minutes of lateral recumbency. Two llamas were severely hypoxemic during this period and were given nasal oxygen for five minutes. Heart rate decreased, but there were no significant changes in blood pressure. Tolazoline significantly shortened the duration of recumbency in the HD treatment. CONCLUSIONS: The HD provided more consistent clinical effects in llamas than did the LD. Intramuscular tolazoline shortens the duration of lateral recumbency in llamas anesthetized with this combination. CLINICAL RELEVANCE: Both doses appear to be very effective in providing restraint in llamas. The LD may be used for procedures requiring a short period of anesthesia or restraint. The HD could be used when a longer duration of anesthesia is desired. Supplemental oxygen should be available if using the HD. Tolazoline (IM) shortened the recovery time with this combination in llamas.  相似文献   

15.
Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.  相似文献   

16.
The effects of a 72 h water deprivation on the absorption--intramuscular (i.m.) and oral and disposition of ampicillin, inulin and para-aminohippuric acid (PAH) were investigated in six sheep. After intravenous (i.v.) administration of ampicillin sodium (10 mg/kg), the water deprivation decreased slightly the initial volume of distribution (0.082 +/- 0.033 vs. 0.055 +/- 0.030 l/kg) but not the steady state volume of distribution. The plasma clearance was significantly decreased (6.21 +/- 1.94 vs. 3.90 +/- 1.92 ml/min/kg) and the mean residence time (MRT) was increased from 22.25 +/- 4.91 to 33.36 +/- 8.16 min. After i.m. administration of ampicillin sodium (20 mg/kg), ampicillin concentrations were systematically higher after a 3-day period of water deprivation than during the control period but the muscular absorption rate was not modified. After oral administration of ampicillin trihydrate (1 g in toto) plasma concentrations were much lower and more persistent than after an i.m. administration and the systemic availability remained low whatever the hydration status. Influences of water deprivation on ampicillin disposition were linked to adaptation of renal function as assessed by inulin and PAH clearances. The therapeutic relevance of the results are discussed for a better definition of dosage regimens for sheep reared in arid environments.  相似文献   

17.
The pharmacokinetics of marbofloxacin (MAR) was compared in geese (Anser Anser domesticus) after single intravenous (IV) and intramuscular (IM) (thigh and pectoral muscles) administrations of 5 mg/kg. Serum concentrations of MAR were determined with high-performance liquid chromatography (HPLC) method. Serum MAR concentrations versus time were analyzed by a noncompartmental method. After IV administration, MAR showed high volume of distribution at steady state (Vdss) of 5.24 ± 1.08 L/kg. The serum body clearance (Cl) and elimination half-life (T1/2λz) of MAR were 0.79 ± 0.07 L hr−1 kg−1 and 6.94 ± 1.12 hr, respectively. The peak of MAR serum concentrations Cmax achieved at one and 0.50 hr after thigh and pectoral IM sites of injections, respectively, were 1.20 and 0.91 μg/ml. Significant differences were found in the mean absorption time (MAT), the systemic bioavailability (F%), and elimination parameters of MAR between two sites of injections, indicating that the absorption was fairly slow and complete after thigh IM injection. The pharmacokinetics of MAR in geese diverged according to the site of IM injection following a parallel study design. We recommend the thigh muscle as IM site of injection to obtain maximum concentrations of the administered drug in geese.  相似文献   

18.
The aim of this study was to compare the effect of an anaesthetic combination given either intramuscularly (IM) or intranasally (IN) for castration of piglets. Forty piglets aged 4 to 7 days were randomly assigned to receive a mixture of ketamine 15 mg kg-1, climazolam 1.5 mg kg-1 and azaperone 1.0 mg kg-1, IN or IM, 10 minutes prior to castration. Physiological parameters were measured. Castration was videotaped for evaluation by 3 independent observers using a scoring system. Reaction and vocalization to the skin incision and cutting of spermatic cord was evaluated and scored (0 = no reaction, 16 = strong reaction). The IN group had a significantly higher (P < 0.01) castration score, compared to the IM group. There was an association between castration score and room temperature in the IN group (with temperatures below 18 "C associated with a higher castration scores (P < 0.001). Heart rate was significantly higher 10 minutes after castration in the IN group (P < 0.05). Respiratory rate was significantly higher in the IM group at time points -5, -1, 10, 20 and 30 (P < 0.05).The IN group was walking significantly (P < 0.0001) faster than the IM group. In conclusion, this combination provides effective anaesthesia for routine castration of newborn piglets when administered IM. IN administration provided shorter recovery times but had significantly higher castration scores.  相似文献   

19.
An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus astnus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45–60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2β was 209 ± 36 min, the apparent volume of distribution (Vd(area)) was 3.34 ± 0.58 L/kg, the total body clearance (ClE) was 1.092 ± 0.123 ± 10--2mL/min/kg and the renal clearance (C1R) was 0.411 ± 0.057 ± 10--2mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances. After intramuscular administration (20 mg/kg), serum NFN concentrations > 0.25 μg/mL (necessary to inhibit the majority of gram-negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing. On the basis of the in vitro-determined minimum inhibitory concentrations of the drug and serum concentrations after multiple dosing, the suggested intramuscular dosage schedules for the treatment of gram-negative bacterial infections in Equidae are 10 mg/kg every 12 h or 20 mg/kg every 24 h.  相似文献   

20.
Five commercially available organic Cu products and reagent-grade CuSO4 x 5H2O (Cu Sulf) were evaluated by polarographic analysis and solubility in 0.1 M K2HPO4-KH2PO4 buffer (pH 5), 0.2 M HCl-KCl buffer (pH 2), or deionized water. Fractions from these solubility tests were evaluated by gel filtration chromatography for structural integrity. The organic sources were Cu lysine complex (Cu Lys), Cu amino acid chelate (Cu AA), Cu proteinate A (Cu ProA), Cu proteinate B (Cu ProB), and Cu proteinate C (Cu ProC). Separation of peaks in the chromatograms for the soluble Cu fraction from deionized water indicated that 77, 31, 69, 94, and 16% of the Cu remained chelated for the above sources, respectively. Two experiments were conducted to estimate the relative bioavailability of Cu from the organic Cu supplements for chicks when added at high dietary concentrations to practical corn-soybean meal diets. Liver Cu concentration increased (P < 0.0001) as dietary Cu increased in both experiments. When Cu Sulf was assigned a value of 100% as the standard, linear regression slope ratios of log10 liver Cu concentration regressed on added dietary Cu concentration gave estimated relative bioavailability values of 124 +/- 5.1, 122 +/- 5.3, and 111 +/- 6.0 for Cu Lys, Cu AA, and Cu ProC, respectively, in Exp. 1. The bioavailability estimates for Cu Lys and Cu AA were greater (P < 0.05) than that for Cu Sulf. Values in Exp. 2 were 111 +/- 7.6, 109 +/- 8.4, and 105 +/- 7.5 for Cu Lys, Cu ProA, and Cu ProB, respectively, and all sources were similar in value for chicks. Solubility of Cu in pH 2 buffer provided the best prediction of bioavailability (r2 = 0.924). Other indicators of chelation integrity and solubility had little value as predictors of bioavailability (r2 < or = 0.445).  相似文献   

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