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1.
Thirty milligrams per kilogram of sulfadiazine/trimethoprim (SDZ/TMP, Tribrissen) was given orally and subcutaneously (s.c.) to two groups of male, Holstein calves. One group was fed milk-replacer throughout the 13-week period of the study while the second group was weaned onto a chopped grain-fiber mixture when 5 weeks old. Serum and urine were assayed for concentrations of unchanged drug. Trimethoprim bioavailability, following oral administration at 1, 6 and 12 weeks of age, is higher in milk-fed calves (non-ruminants) than in grain-fiber-fed calves (ruminants); bioavailability decreases with increasing age in both groups of calves. Serum concentrations above 0.1 micrograms/ml (the level of sensitivity of the assay) could not be obtained in ruminating calves. The rate of SDZ absorption following oral administration, as determined by the Wagner-Nelson method, was very slow in all the calves in this study with average half-life values ranging from 8.2-12.67 h; absorption was slightly faster in ruminating calves. Absorption of SDZ is rate-limiting and determines the biological half-life of the drug; SDZ serum concentrations above 2 micrograms/ml were maintained in all calves for at least 24 h. Following s.c. administration of Tribrissen to 7-and 13-week-old calves, urinary excretion patterns indicated that TMP was slowly released from the injection site; serum concentrations were below 0.1 micrograms/ml. In contrast, absorption of SDZ was very rapid; values for tmax were 1.5-1.8 h. The pharmacokinetic parameters for SDZ were calculated according to a one-compartment open model; neither diet nor age had a significant effect on SDZ disposition following s.c. injection. Subcutaneous administration of 30 mg/kg Tribrissen, b.i.d., may be the best therapeutic regimen; even though measureable concentrations of TMP cannot be achieved in the serum following a single s.c. dose, TMP concentrations should accumulate and, because of its sustained release, provide almost continual potentiation of SDZ.  相似文献   

2.
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   

3.
Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1-2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form. Ninety-nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase-positive staphylococci, Corynebacterium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC less than 4 micrograms/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4-16 micrograms/ml), while all isolates of Corynebacterium (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC greater than 128 micrograms/ml).  相似文献   

4.
The pharmacokinetics of amikacin sulphate were investigated in calves and sheep. Five animals of each species were given 7.5 mg kg-1 intravenously and intramuscularly. After intravenous administration the pharmacokinetic parameters significantly different (P less than 0.01) between calves (first value) and sheep (second value), were: the initial concentration (87.05, 146.6 micrograms ml-1), the apparent distribution volume (350, 200 ml kg-1), the area under curve (5512, 11,018 min micrograms ml-1) and the clearance (1.5, 0.7 ml min-1 kg-1). After dosing intramuscularly the peak concentration (23.5, 34.36 micrograms ml-1), the peak time (45, 75 min) and the area under curve (5458, 9191 min micrograms ml-1) were significantly different (P less than 0.01). No significant differences were observed in the terminal halflife values, suggesting that elimination rate was independent of both route of administration and animal species. The drug in aqueous solution showed a good bioavailability in both animal species (about 0.87 in sheep and greater than 0.99 in calves) despite the greater serum concentrations always attained in sheep.  相似文献   

5.
The minimal inhibitory concentrations (MIC) of amoxycillin and clavulanate-potentiated amoxycillin (amoxycillin:clavulanic acid, 4:1 by weight) were compared for 171 Salmonella, 170 Escherichia coli, and 32 Pasteurella isolates recovered from infected neonatal calves. In the presence of clavulanic acid, the MIC of amoxycillin was reduced to levels less than or equal to 12.5 micrograms/ml for all the Salmonella group B, all the Pasteurella, and for 12 out of the 44 E. coli isolates which were resistant to amoxycillin (MIC greater than or equal to 100.0 micrograms/ml). For isolates sensitive to amoxycillin (MIC less than or equal to 1.56 microgram/ml) there was no change in MIC values in the presence of clavulanic acid. A small proportion of Salmonella and E. coli isolates were resistant to clavulanate-potentiated amoxycillin. In a cross-over trial involving 10 preruminant (2 weeks old) calves, amoxycillin trihydrate and clavulanate-potentiated amoxycillin were administered orally at 10 mg/kg. An analysis of serum amoxycillin level data showed that the pharmacokinetic parameters t1/2ab, Cmax, t1/2 beta, AUC, Cp degree, and f' (estimated drug absorption ratio) were the same after treatment with amoxydrate and clavulanate-potentiated amoxycillin. Administration of clavulanate-potentiated amoxycillin and probenecid resulted in elevation and prolongation of serum amoxycillin levels. Computations showed that in preruminant calves serum amoxycillin concentrations sufficient to inhibit sensitive pathogens can be maintained by oral clavulanate-potentiated amoxycillin treatment at 10 mg/kg TID. At two times that dose rate serum drug concentrations capable of inhibiting 50% of all types of pathogens examined can be maintained.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

6.
A daily oral 5 mg kg-1 dose of clorsulon for 28 days in calves given Fasciola hepatica cysts at 3, 5, and 7 days after initiation of treatment was highly effective in reducing worm burdens (98%) and preventing liver pathology. In similarly infected and treated sheep, clorsulon showed little effect as a prophylactic for delaying the onset of liver pathology. The size of flukes recovered from treated sheep was reduced. Although clorsulon prevented development of fascioliasis in treated calves, the host antibody response was qualitatively similar to that of untreated infected calves, but the magnitude of the response was reduced. Blood clorsulon levels in calves rose to 2.90 micrograms ml-1 within the first week of treatment then fluctuated between 2.65 and 2.90 micrograms ml-1 for the next two weeks. Clorsulon levels in sheep were 0.50-0.60 micrograms ml-1 lower than those in calf blood. The difference in bioavailability of clorsulon between sheep and calves may have contributed to differences in efficacy of the drug.  相似文献   

7.
The minimal inhibitory concentrations (MIC) of mecillinam, a novel beta-amidinopenicillanic acid derivative with unusual activity against Gram-negative bacteria, were compared with the MIC of cephazolin, cephalothin, amoxycillin, oxytetracycline, chloramphenicol, dihydrostreptomycin, neomycin, kanamycin, gentamicin and sulfadoxin/trimethoprim (TMP) against pathogenic Gram-negative bacteria recovered from neonatal calves. The MIC values of mecillinam ranged between 0.05 microgram/ml and 12.5 micrograms/ml, and the MIC90 values were 1.56 micrograms/ml and 3.12 micrograms/ml. The activity of mecillinam against salmonella, Escherichia coli and Pasteurella multocida was similar to or slightly greater than the activities of the first-generation cephalosporins, gentamicin and sulfa/TMP. Mecillinam concentrations less than or equal to 3.12 micrograms/ml inhibited the growth of the majority of isolates which were resistant (MIC90 greater than 100 micrograms/ml) to the other antibiotics studied. The minimum bactericidal concentration (MBC) values of mecillinam were two- to three-fold higher than the MIC values. The two-compartment open model was appropriate for the analysis of serum mecillinam concentrations measured after intravenous administration. The distribution half-life (t1/2 alpha) was 11.7 min, the elimination half-life (t1/2 beta) was 53.3 min, and the apparent volume of distribution (Vd (area)) and the distribution volume at steady state (Vd (ss)) were 0.568 and 0.896 l/kg, respectively. The drug was quickly absorbed after intramuscular (i.m.) injection; peak serum drug concentrations were directly related to the dose administered. They were obtained 30 min after treatment and the i.m. t1/2 was approximately 65 min.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

8.
Age-related changes in the absorption and distribution patterns of trimethoprim/sulfadiazine were studied following oral or subcutaneous administration of 15 mg/kg of the drug combination in calves. Following oral administration, the time course of trimethoprim/sulfadiazine appearance and dissipation in serum, synovial fluid and urine was followed for periods up to 48 hours in calves one day, one week and six weeks of age. The profiles of drug appearance-disappearance in these body fluids were also determined after subcutaneous administration in seven week old calves. The peak serum and synovial fluid levels of trimethoprim/sulfadiazine achieved following oral administration were substantially lower with increasing maturation. In ruminating (six and seven week old) calves, subcutaneous or oral administration of the combination led to high serum levels of sulfadiazine but little or no serum trimethoprim was detected in animals at this age. The data indicate that, while therapeutic concentrations and optimum ratios of the drugs may be achieved for extended time periods in neonatal life, this dosage is unable to produce optimum serum and synovial fluid concentrations as the calves mature.  相似文献   

9.
The oral absorption and bioavailability of flumequine was studied in 1-, 5- and 18-week-old calves following intravenous and oral administration of different formulations of flumequine (Flumix, Flumix C and pure flumequine). Increasing age had a negative influence on the Cmax after the administration of Flumix, based on a larger VD in the older calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the Cmax of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C, for which it was 75.9 +/- 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 +/- 2.3% for Group B, to 41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight Flumix twice daily in 1-week-old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 micrograms/ml of the target bacteria. In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the Cmax of flumequine.  相似文献   

10.
A three-way crossover study was carried out in 10 dogs and nine cats to establish the pharmacokinetic parameters of the semi-synthetic cephalosporin antibiotic, cephalexin sodium, when administered orally, subcutaneously or intramuscularly. Ten dogs received a subcutaneous or intramuscular injection of 10 mg/kg bodyweight cephalexin or an oral dose of three 50 mg cephalexin tablets; the peak serum concentrations achieved were 24.9, 31.9 and 18.6 micrograms/ml, respectively, and the times taken to reach these peak levels were 1.2, 0.9 and 1.8 hours. Nine cats received either a subcutaneous or intramuscular dose of 0.25 ml cephalexin suspension (approximately 20 mg/kg bodyweight) or an oral dose of one 50 mg tablet; the peak serum concentrations achieved were 54.0, 61.8 and 18.7 micrograms/ml for the subcutaneous, intramuscular and oral administrations respectively, with times to peak concentrations of 1.1, 0.7 and 2.6 hours.  相似文献   

11.
The minimal inhibitory concentration (MIC) of flumequine for 249 Salmonella, 126 Escherichia coli, and 22 Pasteurella multocida isolates recovered from clinical cases of neonatal calf diarrhoea, pneumonia and sudden death was less than or equal to 0.78 microgram/ml. The pharmacokinetics of flumequine in calves was investigated after intravenous (i.v.), intramuscular (i.m.) and oral administration. The two-compartment open model was used for the analysis of serum drug concentrations measured after rapid i.v. ('bolus') injection. The distribution half-life (t1/2 alpha) was 13 min, elimination half-life (t1/2 beta) was 2.25 h, the apparent area volume of distribution (Vd(area)), and the volume of distribution at steady state (Vd(ss)) were 1.48 and 1.43 l/kg, respectively. Flumequine was quickly and completely absorbed into the systemic circulation after i.m. administration of a soluble drug formulation; a mean peak serum drug concentration (Cmax) of 6.2 micrograms/ml was attained 30 min after treatment at 10 mg/kg and was similar to the concentration measured 30 min after an equal dose of the drug was injected i.v. On the other hand, the i.m. bioavailability of two injectable oily suspensions of the drug was 44%; both formulations failed to produce serum drug concentrations of potential clinical significance after administration at 20 mg/kg. The drug was rapidly absorbed after oral administration; the oral bioavailability ranged between 55.7% for the 5 mg/kg dose and 92.5% for the 20 mg/kg dose. Concomitant i.m. or oral administration of probenecid at 40 mg/kg did not change the Cmax of the flumequine but slightly decreased its elimination rate. Flumequine was 74.5% bound in serum. Kinetic data generated from single dose i.v., i.m. and oral drug administration were used to calculate practical dosage recommendations. Calculations showed that the soluble drug formulation should be administered i.m. at 25 mg/kg every 12 h, or alternatively at 50 mg/kg every 24 h. The drug should be administered orally at 30 and 60 mg/kg every 12 and 24 h, respectively. Very large, and in our opinion impractical, doses of flumequine formulated as oily suspension are required to produce serum drug concentrations of potential clinical value.  相似文献   

12.
The minimal inhibitory concentrations (MIC) of carbenicillin, ticarcillin and BL-P 1654 for gram-negative udder pathogens were determined using the agar plate dilution method. The MIC of the drugs for 50% and 90% of the isolates examined ranged for Escherichia coli and Aerobacter spp. from 1.56 to 25 micrograms/ml, and for Klebsiella spp. and Pseudomonas spp. from 3.12 to 50 micrograms/ml. The Serratia spp. were relatively non-susceptible for the drugs studied (MIC greater than 50 micrograms/ml). Each drug was administered intravenously at 5 g and 15 g per cow to different groups of cows with normal and inflamed quarters of the udder. Distribution and elimination kinetic parameters calculated from serum drug level data were very similar to those of other beta-lactam antibiotics. Although drug concentrations in milk from inflamed quarters were higher than in milk from normal quarters, they were considerably below the MIC for the majority of gram-negative udder pathogens. The data suggest that parenteral treatment of gram-negative udder infections with carbenicillin, carfecillin, ticarcillin and BL-P 1654 at the dose levels used in the present study is unlikely to result in a bacteriological cure and would probably be clinically ineffective.  相似文献   

13.
The in vitro activity of 10 cephalosporin antimicrobial agents against 75 isolates of methicillin-susceptible Staphylococcus pseudintermedius derived from dogs was assessed. The lowest minimal inhibitory concentration for 90% of strains (MIC90) values obtained were for cephalothin, cefovecin, and cefazolin (0.12 ug/mL), followed by ceftiofur and cefoxitin (0.25 ug/mL), cefpodoxime (0.5 ug/mL), and cefaclor and cefadroxil (1 ug/mL). The highest MIC90 values were found for cephalexin and cefixime (2 ug/mL). In this in vitro study, sensitivity to cephalothin was indicative of cephalexin susceptibility, although there were marked differences in MICs. Cephalothin susceptibility was not indicative of susceptibility to all tested cephalosporins, nor was there a clear trend in susceptibility based on cephalosporin generation.  相似文献   

14.
The present investigation was undertaken to improve regimens dosage of amoxycillin, chloramphenicol or trimethoprim-sulphadiazine in Salmonella dublin infected veal calves. The pharmacokinetics of these drugs were studied after i.v., oral, and i.m. administration (bioavailability, local irritation at the injection site, volume of distribution, and elimination half life). The most important conclusion was that amoxycillin, chloramphenicol, and trimethoprim were suitable for oral administration to veal calves, although the bioavailability of chloramphenicol and trimethoprim was significantly less when concurrently administered with a milk replacer. In vitro, the antibacterial activities of these drugs were compared. Addition of trimethoprim to sulphadiazine lowered its MIC for S. dublin, but sulphadiazine reduced the killing rate compared to that of trimethoprim alone. In the efficacy studies the activities of several serum enzymes and the plasma concentrations of Fe, Zn, and Cu were measured, but it appeared, that these biochemical parameters were no better than the clinical parameters body temperature and body weight. Using optimal dosage regimens based on MIC values and blood levels, treatment with either of the three drugs was of equal efficacy.  相似文献   

15.
Twelve calves were raised helminth-free until 9 weeks of age when six were orally inoculated with 100,000 Ostertagia ostertagi infective stage larvae (L3). Three uninfected and three experimentally infected calves received intradermal injections of sterile saline and soluble larval extract (SLE) from O. ostertagi L3 with a protein concentration ranging from 1 to 200 micrograms ml-1. Biopsies were performed 48 h post-injection. A kinetic study was performed on the remaining six calves, three infected and three uninfected, using a 100 micrograms ml-1 concentration of SLE and taking biopsies 1, 4, 8, 12, 24, and 72 h post-injection at both the saline and SLE-injected sites. All calves had an immediate wheal and increase in skin thickness at the SLE-injected sites. The numbers of eosinophils infiltrating SLE-injected sites as compared to saline-injected sites were significant in both uninfected and infected calves, but the infected calves had significant numbers to a wider range of SLE concentrations and had significantly higher numbers than uninfected calves in the kinetic study. Infected calves also had significant numbers of basophils in the dose response study at concentrations of 5 and 100 micrograms ml-1 SLE. Neutrophil infiltration was similar in both groups and was significant at SLE-injected sites early in the kinetic study. Detectable mast cells were decreased in SLE-injected sites of infected animals and perivascular accumulation of mononuclear and some polymorphonuclear cells was observed in the deep dermis of infected animals.  相似文献   

16.
Twelve 9-week-old calves were divided into four groups; two groups were maintained helminth-free as controls and the other groups were given Ostertagia ostertagi infective-stage larvae (L3) orally. One group received 100,000 L3 as a single inoculum and the other group received L3 in increasing dosages at weekly intervals for 8 consecutive weeks. The blastogenic responses to concanavalin A (Con A), phytohemagglutinin (PHA), and a soluble larval antigen from O. ostertagi (SLA) of peripheral blood lymphocytes were evaluated using tritiated thymidine incorporation into DNA as a measure of blastogenesis. The responses to Con A of all infected calves were significantly depressed while the responses to PHA were not. SLA, at concentrations of 4 micrograms ml-1 and above, caused blastogenic activity in lymphocytes from uninfected calves. Using SLA at 1 microgram ml-1 in lymphocyte cultures supplemented with autologous serum, an antigen-induced blastogenic response was detected in calves receiving serial inoculations of L3.  相似文献   

17.
Cefoperazone pharmacokinetics were studied in unweaned calves. The antibiotic was administered to 10 calves intravenously, to eight calves intramuscularly at 20 mg kg-1 and to 10 calves intramuscularly at 20 mg kg-1 together with probenecid at 40 mg kg-1. Serum concentration versus time data were analysed by non-compartmental methods based on the statistical moment theory. The intravenous data were also fitted by a linear, open two-compartment model. The terminal halflife of cefoperazone was 127.9 +/- 28.2 min (mean +/- SD) after intravenous and 136.9 +/- 19.6 min after intramuscular administration. The t1/2 was increased to 257.3 +/- 127.3 min by the co-administration of probenecid. The total body clearance was 8.16 +/- 1.60 ml min-1 kg-1 and the volume of distribution at steady state was 0.713 +/- 0.167 litre kg-1. The mean residence time values were 87.2 +/- 10.6 min after intravenous and 140.3 +/- 20.6 min after intramuscular injection and were increased to 264.5 +/- 99.8 min by the co-administration of probenecid. The estimated mean absorption time was 53.1 min and the estimated bioavailability after intramuscular administration was 76.3 per cent. The minimal inhibitory concentration (MIC90) values of cefoperazone ranged from 0.5 to 2 micrograms ml-1 for Escherichia coli, salmonella groups C, D and E and Pasteurella multocida isolates. Salmonella group B strains appeared to be highly resistant to cefoperazone with MIC90 greater than 32 micrograms ml-1. There were no significant differences between the pharmacokinetic variables calculated by statistical moment theory or compartmental analysis indicating central compartment output of cefoperazone.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.  相似文献   

19.
Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC50) of field isolates of Escherichia coli. Salmonella and Pasteurella were 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk-fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.  相似文献   

20.
The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.  相似文献   

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