ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00062.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high‐performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half‐life (t1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution (Vd(ss)) 1.1±0.2 L/kg and the total body clearance (ClB) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration (Cmax) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half‐life (t1/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [3H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1‐4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00063.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Six healthy mares ranging in age from 6 to 12 years and weighing from 415 to 540 kg were used to determine the rectal bioavailability of ketoprofen. For the rectal administration, three different formulations, each containing 1 g of ketoprofen, were administered in a fatty and a hydrophilic suppository base and as a liquid suspension. An average elimination half‐life of 1.3 h (±1.2) was found. The average value for the total plasma clearance (ClT) was 131.9 mL/min.kg (range 95‐183.5). The volume of distributionVd(area)was 255 mL/kg and the mean residence time (MRT)P = 0.05; Friedman test). Despite the low rectal bioavailability obtained in this study, there was some evidence for the clinical effectiveness of the rectal formulat

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00064.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four‐way, randomized, crossover experiment in rabbits. Attention is focused on bioequivalence based on plasma concentration vs. time profiles to study whether the rabbit is a good model to detect differences inin vivodelivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products. In all products, penicillin was present as a suspension. Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed. With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin/dihydrostreptomycin fixed combination products for intramuscular injection. A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animal

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00065.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A bioequivalence study with three penicillin/dihydrostreptomycin fixed combination products for intramuscular administration was performed in dairy calves. In addition to plasma concentrations of penicillin and dihydrostreptomycin, creatine phosphokinase concentrations were determined during a period of 72 h after administration of the drug products. Considerable differences were observed in the pharmacokinetics of penicillin from the three products. Although the extent of absorption was similar for all products, one product showed a significantly slower release from the site of injection. Except for theAUC, the 90% confidence intervals for these parameters exceeded the acceptable range of 0.80‐1.20. Therefore, these products are not bioequivalent with respect to the rate of absorption of penicillin. Concerning the pharmacokinetics of dihydrostreptomycin in calves, it could not be concluded that the products were bioequivalent, since the 90% confidence intervals of the ratios forCmax,tmaxandMRTexceeded the range of 0.80‐1.20. From this study in calves, it was also found that the product with the slowest release of penicillin from the injection site caused the most severe tissue damage, based on plasma creatine phosphokinase concentrations. Comparing the results from this study in calves with those from a previous study in rabbits, it can be concluded that the rabbit is a good animal model that could substitute for large animals, at least calves, in bioequivalence studies for penicillin/dihydrostreptomycin fixed combination produ

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00066.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256‐290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated withPasteurella haemolytica(106CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non‐infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur‐equivalent microbiological activity were measured by high‐pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and antimicrobial activity inP. haemolytica‐infected tissue chambers were significantly higher than those in non‐infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected withP. haemolytica. Antibiotic activity‐concentration ratios were lower in plasma and infected chamber fluid compared with non‐infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non‐infected chamber fluid suggests that active drug is reversibly bound to proteins. Protein‐bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00067.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Drug disposition, including hepatic drug metabolism, is markedly affected by infection, inflammation and other conditions that invoke the acute phase response. In the present study, anEscherichia colilipopolysaccharide (LPS)‐induced acute phase response model was developed in pigs. This model was used to study the effects of the acute phase response on drug disposition and hepatic drug metabolismin vivoand in microsomal preparations. The results obtained were compared with those fromActinobacillus pleuropneumoniae‐infected pigs. Intermittent intravenous administration of LPS induced a mild acute phase response as evidenced by increased rectal body temperatures, anorexia and increased cytokine (TNF‐α and IL‐6) serum levels within 1‐2 h after the first LPS injection. The acute phase response is associated with a pronounced decrease of antipyrine plasma clearance (control 8.5 ± 0.8vs.LPS 2.2 ± 0.7 mL/min.kg). Furthermore, total cytochrome P450 content and microsomal cytochrome P450‐dependent activities were significantly decreased after 24 h. The decrease in cytochrome P450 activities was accompanied by losses of cytochrome P4501A and P4503A apoproteins. The microsomal glucuronidation rate of 1‐naphthol was not affected in LPS‐treated pigs. Comparing the LPS model with our previous findings in theActinobacillus pleuropneumoniaemodel showed a remarkable similarity with regard to the effects on hepat

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00068.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

To investigate the vascular smooth muscle dysfunction of septic shock,in vitroisometric responses to phenylephrine (PE) and acetylcholine (ACh) were evaluated in aortic rings, with and without endothelium (± E), removed from male Wistar rats 1.5, 3 and 6 h after intravenous (i.v.) administration of 5 mg/kg lipopolysaccharide (LPS) or vehicle. A reduction in maximum contraction (±E) and sensitivity (‐E) to PE were identified at 6 but not at 1.5 or 3 h. Maximum relaxation to ACh (+ E) was not affected by LPS treatment but sensitivity was increased at 1.5 and 3 h. Having identified 6 h as the time at which the most pronounced changes were observed, further studies at this interval found that maximum contraction to potassium chloride (±E), prostaglandin F2a(+ E) and detomidine (‐E) and relaxation to salbutamol (‐E) were less in aortic rings from endotoxaemic rats. Sensitivity to KCl (±E), PGF2a(‐ E) and detomidine (‐ E) was also reduced. Relaxation to sodium nitroprusside and atrial natriuretic peptide was not changed. These results suggest that attenuated pressor responses to a variety of vasoactive agents may be expected in patients 6 h after systemic exposure to endotoxin and that this vasoplegia may influence the vascular side‐effects of the

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00069.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Thein vitroactivities of 14 anti‐microbial agents were determined against 92 strains ofE. coliisolated from lambs (60 strains) and kids (32 strains) affected by neonatal diarrhoea. The overall percentage of resistant strains to streptomycin, sulphadimethoxine and tetracycline was very high (above 70%). A high level of resistance (from 30% to 50%) to ampicillin, kanamycin, neomycin and chloramphenicol was also detected. TheE. colistrains were highly susceptible to cephalosporins, polymyxin and quinolones. Most of the strains showed multiresistance: 77.2% of isolates were resistant to at least two antibiotics, 55.4% were resistant to at least four antibiotics and 33.7% were resistant to at least six antibiotics. A total of 34 antibiotypes could be distinguishe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00070.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00071.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY