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1.
The pharmacokinetics of 4-methylimidazole (4MI), a toxin found in ammoniated forage, was studied after i.v. infusion or oral administration of a single dose of 20 mg 4MI/kg BW to sheep. A two-compartment open model was used to describe i.v. infusion data. Oral data were described by a one-compartment open model. A rapid distribution phase (t1/2 alpha = 28 min) was observed after i.v. infusion. The biological half-lives obtained after i.v. infusion (t1/2 beta = 9.72 h) and oral dosing (t1/2 beta = 9.37 h) were similar. The bioavailability of oral 4MI was .69, with a relatively rapid absorption phase (t1/2abs = 1.52 h). The relatively large volume of distribution (61.6 and 65.8 liters for i.v. infusion and oral dosage, respectively) indicates that 4MI is distributed in the extravascular compartment. A dose of 20 mg/kg BW did not cause any apparent ill effects to the animals.  相似文献   

2.
Pharmacokinetic parameters of florfenicol were determined in 10 adult sheep (five wethers and five ewes) after a single 40 mg/kg intravenous (i.v.) dose, and three daily subcutaneous (s.c.) doses of 40 mg/kg of a commercial preparation (Nuflor((R))). The concentration of florfenicol in serum samples was assayed using a proprietary HPLC assay method, and pharmacokinetic parameters derived for individual animal data by each route using compartmental and noncompartmental approaches. Two animals (one male and one female) were excluded due to observed i.v. dosing problems, and a biexponential model was found to fit the i.v. data well for six of the other eight animals. Data from two males showed prolonged low concentrations of florfenicol in serum and were better fit by a three-compartment model. The mean +/- SD for the half-lives of the distribution and elimination phases for the six sheep best fit with a two-compartment model were 0.069 +/- 0.018 and 1.01 +/- 0.09 h respectively, and for the V(d(ss)) and clearances were 0.503 +/- 0.035 L/kg and 366 +/- 53 mL/h/kg respectively. The data collected during the s.c. multiple dose study were analyzed using noncompartmental methods only. The bioavailability (F%) after s.c. dosing was calculated in three ways to compare estimation methods as steady-state had not been reached and single dose s.c. data were not obtained past 24 h. Using the AUC(0--24) and AUC(0--> infinity ) from the first dose, the F% values averaged 27 and 40% respectively. Using the AUC(0--> infinity ) for all doses, the F% was 65%. Calculations of the mean time during which the serum concentration exceeded 0.5 and 1.0 microg/mL were 105 +/- 3.9 and 74.7 +/- 12.2 h respectively.  相似文献   

3.
Twenty-four sheep (38.0–54.1 kg body wt) were allocated 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 two-week washout between injections. After another two-week washout period, 12 sheep were selected and dosed with ceftiofur sodium i.m. for five consecutive days at either 1.1 or 2.2 mg CFAE/kg. After all injections, blood samples were obtained serially for determination of serum concentrations of ceftiofur and metabolites. The terminal phase half-lives derived from the last 3–5 concentration-time points were 350 and 292 min (harmonic means) after i.v. doses of 1.1 and 2.2 mg/kg, respectively, and 389 and 459 min after i.m. doses of 1.1 and 2.2 mg/kg, respectively. The i.m. bioavailability of ceftiofur sodium in sheep was 100%, and the area under the curve from time 0 to the limit of quantitation ( AUC 0–LOQ) was dose-proportional from 1.1–2.2 mg CFAE/kg body wt in sheep. After 5 daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE/kg there was minimal accumulation of drug in serum as assessed by the observed maximum serum concentration ( C max), and serum concentrations were dose-proportional after the multiple dosing regimen.  相似文献   

4.
The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.  相似文献   

5.
The pharmacokinetics of the anti-convulsant phenytoin were investigated in clinically healthy horses after oral (p.o.) and intravenous (i.v.) administration. A single dose of phenytoin (8.8 mg/kg body weight) was given i.v. as a bolus to nine horses and one horse received 13.2 mg/kg. A two-compartment open model was used to describe the disposition of phenytoin. Four of the horses that received an i.v. dose (three at 8.8 mg/kg and one at 13.2 mg/kg) were then given the same dose 3 days later by the oral route. Phenytoin achieved a peak concentration in serum within 1–4 h after p.o. administration and was poorly absorbed with a bioavailability of 34.5 ± 8.6%. Oral dosage regimens were calculated on the basis of a dosing interval of 8 h to provide average serum steady-state concentrations of 5 and 10 μg/ml for phenytoin.  相似文献   

6.
REASONS FOR PERFORMING STUDY: Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. OBJECTIVE: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. METHODS: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. RESULTS: Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2-compartment open model. The disposition of i.m. administered danofloxacin was best described by a one-compartment model. The terminal half-lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean +/- s.d. 88.48 +/- 11.10% and Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 0.21 +/- 0.07 mg/l. CK activity following i.m. dosing increased 3-fold over pre-injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. CONCLUSIONS: Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. POTENTIAL RELEVANCE: Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.  相似文献   

7.
The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by high-performance liquid chromatography.
  There was considerable inter individual variability in pharmacokinetic parameters. The mean (SD) values for systemic clearance ( Cl ) and steady-state volume of distribution ( V ss) were 494 (43.6) mL/h/kg and 1471 (578) mL/kg, respectively. Although the rate of cisapride absorption was quite rapid, only about half the i.g. dose was absorbed systemically. The average terminal half-life ( t ½) calculated over three i.g. doses was 2.06 h and that for i.v. administration was 2.12 h. The pharmacokinetics of cisapride from 0.1 mg/kg to 0.4 mg/kg were independent of the i.g. dose.  相似文献   

8.
OBJECTIVE: To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs. DESIGN: Randomized 3-way crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: A single dose of aminophylline (11 mg x kg(-1) 15 mg x lb(-1)], i.v., equivalent to 8.6 mg of theophylline/kg 13.9 mg x lb(-1) or extended-release theophylline tablets (mean dose, 15.5 mg x kg(-1) [7.04 mg x lb9-1), PO) or capsules (mean dose, 15.45 mg x kg(-1) [7.02 mg x lb(-1)], PO) was administered to all dogs. Blood samples were obtained at various times for 36 hours after dosing; plasma was separated and immediately frozen. Plasma samples were analyzed by use of fluorescence polarization immunoassay. RESULTS: Administration of theophylline i.v. best fit a 2-compartment model with rapid distribution followed by slow elimination. Administration of extended-release theophylline tablets and capsules best fit a 1-compartment model with an absorption phase. Mean values for plasma terminal half-life, volume of distribution, and systemic clearance were 8.4 hours, 0.546 L x kg(-1), and 0.780 mL x kg(-1) x min(1), respectively, after i.v. administration of theophylline. Systemic availability was > 80% for both oral formulations. Computer simulations predicted that extended-release theophylline tablets or capsules administered at a dosage of 10 mg x kg(-1) (4.5 mg x lb(-1)), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range of 10 to 20 microg x mL(-10. CONCLUSIONS AND CLINICAL RELEVANCE: Results of these single-dose studies indicated that administration of the specific brand of extended-release theophylline tablets or capsules used in this study at a dosage of 10 mg x kg(-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 microg x mL(-1)) in healthy dogs.  相似文献   

9.
Bioavailability of amoxycillin in pigs   总被引：4，自引：0，他引：4  
Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross-over design to examine the bioavailability ( F ) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing 'conventional' duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high-performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of non-compartmental methods.
  Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time ( MRT ) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 μg/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.  相似文献   

10.
The pharmacokinetics and systemic bioavailability of amoxycillin were investigated in clinically healthy, broiler chickens (n = 10 per group) after single intravenous (i.v.), intramuscular (i.m.), and oral administrations at a dose of 10 mg/kg body weight. The plasma concentrations of amoxycillin were determined using high-performance liquid chromatography (HPLC) and the data were subjected to compartmental and non-compartmental kinetic analyses. Following single i.v. injection, all plasma amoxycillin data were described by a two compartment-open model. The elimination half-lives of amoxycillin were 1.07 h, 1.09 h and 1.13 h after single i.v., i.m. and oral administration, respectively. The total body clearance (Cl(B)) of amoxycillin was 0.80 (L/h)/kg and the volume of distribution calculated as V(d(area)) was 1.12 L/kg, respectively after i.v. administration. Substantial differences in the resultant kinetic data were obtained by comparing the plasma concentration profiles after i.m. injection with that after oral administration. The systemic i.m. bioavailability of amoxycillin was higher (77.21%) than after oral (60.92%) dosing. In vitro, the mean plasma protein binding of amoxycillin amounted to 8.27%. Owing to high clearance of amoxycillin in birds in our study, a plasma level was maintained above 0.25 microg/ml for only 6 h after i.m. and oral routes of administration and consequently frequent dosing may be necessary daily.  相似文献   

11.
The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.06 l/kg, and 0.06 +/- 0.01 l/kg/h (mean +/- SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P less than 0.05) for the immediate-release aminophylline (13.8 +/- 2.8 h) and sustained-release theophylline (18.2 +/- 2.3 h) formulation. Immediate-release aminophylline tablets quickly achieved peak theophylline plasma concentration of 11.51 +/- 1.4 micrograms/ml at 1.6 +/- 0.6 h while the sustained-release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 +/- 1.3 micrograms/ml at 7.3 +/- 1.0 h. Absolute bioavailability was 87% for the immediate-release and 97% for the sustained-release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained-release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough-peak theophylline plasma concentrations between 6 and 17 micrograms/ml.  相似文献   

12.
The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.  相似文献   

13.
The aim of this study was to determine the influence of mechanically induced duodenal distension (DD) and PD 140.548 N-methyl-D-glucamine (a specific peptide antagonist of a CCK1 receptor) premedication on mechanographical reticulo-ruminal activity, animal general behaviour, catecholamines (CA) and the blood plasma cortisol levels, as well as the clinical symptoms of visceral pain induced by DD in sheep. After 24 h fasting, 6 animals, Polish merino sheep were praeanaesthetised by i.m. injection of ketamine (20 mg x kg(-1) b.w.) and anaesthetised with i.v. infusion of pentobarbital (20 mg x kg(-1) b.w.) and a permanent stainless steel cannula (gate cannula) was inserted inside the lateral cerebral ventricle (controlled by cerebrospinal fluid efflux) 10 mm above the bregma and 5 mm laterally from the midline suture using stereotaxic method. Under the same general anaesthesia and analgesia a T-shaped silicon cannula, was inserted into the duodenum (12 cm from pylorus) and a second one was inserted into the dorsal sac of the rumen. During 7 consecutive days after surgery each animal was treated i.m. with procaine penicillin (300000 I.U..kg(-1) b.w.), dihydrostreptomycine (DHS, 10 microg x kg(-1) b.w.), prednisolone acetate 1.2 mg x kg(-1) b.w.) together and i.m. injection of ketamine (20 mg x kg(-1) b.w.), separetely. The influence of PD 140.548 N-methyl-D-glucamine on the unfavourable effects of duodenal distension using a 10 cm long balloon filled with 40 and 80 ml (DD40 and DD80) water at animal body temperature was investigated in this study. Five minutes DD40 and DD80 caused an immediate and compete inhibition of the reticulo-ruminal frequency, a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other symptoms of pain, proportionally to the degree of intestinal distension. Intracerebroventricular (i.c.v.) administration of PD 140.548 alone at a dose of 0.25, 0.5, 1 or 2 mg in toto did not significantly change the reticulo-ruminal motility, CA and cortisol concentrations, but 10 min after the i.c.v. infusion (or 10 min before DD) at a dose 1 and 2 mg in toto , it completely blocked the increase of blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentrations for 20 min. In the some time it prevented the reticulo-ruminal atony provocked by DD. It is concluded that PD 140.548 N-methyl-D-glucamine--an antagonist of the central CCK1 receptor can be an effective analgesic agent in duodenal pain. This action is due to the inhibition of peripheral CCK1 type receptor in the central descending nerve pathway, facilitating pain transmission in sheep perhaps in the hypothalamic-pituitary-adrenal axis.  相似文献   

14.
The pharmacokinetic properties of pentoxyfylline and its metabolites were determined in healthy chickens after single intravenous and oral dosage of 100 mg/kg pentoxyfylline. Plasma concentrations of pentoxyfylline and its metabolites were determined by a validated high-performance liquid chromatographic method. After intravenous (i.v.) and oral (p.o.) administration, the plasma concentration-time curves were best described by a one-compartment open model. The mean elimination half-life (t(1/2el)) of pentoxyfylline was 1.05 h, total body clearance 1.90 L/h x kg, volume of distribution 2.40 L/kg and the mean residence time was 2.73 h, after i.v. administration. After oral dosing, mean maximal plasma concentration of pentoxyfylline was 4.01 microg/mL and the interval from p.o. administration until maximum concentration was 1.15 h. The mean oral bioavailability was found to be 28.2%. Metabolites I, IV and V were present in chicken plasma after both i.v. and p.o. administration, with metabolite V being the most dominant.  相似文献   

15.
Based on its ideal PK/PD ratios, doxycycline hyclate (DOX‐h), a time‐dependant antibacterial, is ideally expected to achieve sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer‐based matrix was used to produce a 10% long‐acting injectable preparation (DOX‐h‐LA) and its serum concentrations vs. time profile investigated after its injection to pigs in the pericaudal s.c. by parallel design. Results were compared with the forced oral bolus dose and i.v. pharmacokinetics of DOX‐h. For this study, 12 recently weaned pigs per group were included in this trial, and a dose of 20 mg/kg was injected in all cases. DOX‐h‐LA showed the greatest values for bioavailability (115.38%); maximum serum concentration (Cmax) value was 1.5 ± 0.2 with a time to reach Cmax of 3.41 ± 0.04 h and an elimination rate constant of 70.93 ± 0.87 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose interval of at least 5 days can be achieved for DOX‐h‐LA, whereas p.o. and i.v. dosing of DOX‐h may only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this trial, and no visible remnants of the preparation were detected neither fibrosis was observed after a thorough macroscopic and histopathological analysis.  相似文献   

16.
Phenylbutazone was administered orally and intravenously at a dose of 5 mg/kg to healthy cows and to cows positive for bovine leukaemia virus (BLV). Pharmacokinetic parameters and bioavailability were investigated. No differences were seen in the parameters between the healthy and BLV positive animals. The biological half-lives ranged from 31.4 to 82.1 h after intravenous administration and from 38.6 to 78.2 h after oral administration. The mean value of the apparent volume of distribution was 0.09 litres/kg. Total body clearance ranged from 0.78 to 1.94 ml/kg/h. The average systemic availability was 67.5% with a wide variation among the animals (range 41.9–95.5%). Based on the disposition kinetics and on the therapeutic concentration range suggested in man, an oral loading dose ranging from 10 to 20 mg/kg and a daily maintenance dose ranging from 2.5 to 5 mg/kg can be proposed.  相似文献   

17.
Maropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs; it is administered by subcutaneous (s.c.) injection at 1 mg/kg, or orally (p.o.), in tablet form, at either 2 or 8 mg/kg depending on indication. The absolute bioavailability of maropitant was markedly higher (90.7%) following s.c. injection than after oral administration (23.7% at the 2 mg/kg dose and 37.0% at the 8 mg/kg dose). First-pass metabolism contributes to the low bioavailability of maropitant following oral administration. The difference in bioavailability between the two oral doses reflects the nonlinear kinetics characterizing the disposition of maropitant within the 2-8 mg/kg dose range. Systemic clearance of maropitant following intravenous (i.v.) administration was 970, 995 and 533 mL/h.kg at doses of 1, 2 and 8 mg/kg, respectively. Nonproportional kinetics were observed for p.o. administered maropitant at doses ranging from 2 to 16 mg/kg but dose proportionality was demonstrated at higher doses (20-50 mg/kg). Linearity was also demonstrated following s.c. administration at 0.5, 1 and 2 mg/kg. Maximum plasma drug concentration (Cmax) occurred 0.75 h (tmax) after s.c. administration at 1 mg/kg, and at 1.7 and 1.9 h after oral administration of 8 and 2 mg/kg doses, respectively. The apparent terminal half-life of maropitant was 7.75, 4.03 and 5.46 h after dosing at 1 mg/kg (s.c.), 2 mg/kg (p.o.) and 8 mg/kg (p.o.), respectively. Feeding status had no effect on oral bioavailability. Limited accumulation occurred following once-daily administration of maropitant for five consecutive days at 1 mg/kg (s.c.) or 2 mg/kg (p.o.). At the dose of 8 mg/kg (p.o.) once daily for two consecutive days, the mean AUC(0-24h) (second dose) was 218% that of the first dose value. Urinary recovery of maropitant and its main metabolite was minimal (<1%), thus supporting the evidence that maropitant clearance is primarily hepatic.  相似文献   

18.
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   

19.
Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10 mg/kg) of intravenous (i.v.) or oral administration in freshwater at a mean water temperature of 25.4 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After i.v. florfenicol injection, the terminal half-life (t(1/2)), volume of distribution at steady state (V(ss)), and central volume of distribution (V(c)) were 8.25 h, 0.9 and 0.381 L/kg, respectively. After oral administration of florfenicol, the terminal t(1/2), C(max), T(max), and oral bioavailability (F) were 9.11 h, 7.6 μg/mL, 9.2 h, and 1.09, respectively. There was a lag absorption time of 1.67 h in oral dosing. Results from these studies support that 10 mg florfenicol/kg body weight in channel catfish is an efficacious dosage following oral administration.  相似文献   

20.
Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8% +/- 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg. In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.  相似文献   

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