ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00076.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Oral administration of [14C] fenbendazole (FBZ) at a dose of 5.Omg/kg leads to the presence of radiolabel in the milk of lactating dairy cows. However, the maximum mean concentration of total FBZ equivalents quantitated to one‐third of the recommended safe concentration in milk (1.67 μg/mL). The label is equally distributed to the fat and aqueous portions of the milk. The maximum level, in general, is attained approximately 24‐36 h after drug administration, with the highest levels ranging from 24 to 48 h after administration. The residues rapidly deplete, attaining levels of 10‐20ng/mL by day 5, and are essentially undetectable by radiolabel monitoring by day 6. Extraction of the milk by matrix solid phase dispersion indicated that the label was distributed between traces of the parent drug, FBZ, and predominantly, the FBZ sulphoxide (SO) and sulphone (SO2) metabolites. No other radiolabelled peaks were observed. Based on these data the metabolites of FBZ, FBZ‐sulphone and FBZ‐sulphoxide, could be used as marker residues for monitoring the administration of FBZ to lactating

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00077.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Twenty‐six healthy female pigs weighing 19.5‐33 kg were used in three separate experiments. The animals were fed individually twice a day. Trimethoprim/sulphadiazine (TMP/SDZ) formulation was added to feed in the amount of 6 mg/kg bw (TMP) and 30 mg/kg bw (SDZ). TMP and SDZ concentrations in blood plasma, muscles, liver and kidneys were measured. Pharmacokinetic parameters show that the absorption of TMP from the alimentary tract in pigs is faster than the absorption of SDZ, and the elimination of TMP is slower than that of SDZ. The absorption half‐lives were 0.96 (TMP) and 2.24 h (SDZ), whereas elimination half‐lives were 5.49 (TMP) and 4.19 h (SDZ). The observed TMP:SDZ ratios in blood plasma after multiple dose administration ranged from 1:11.4 to 1:23.2. One day after administration of the last dose of TMP/SDZ the plasma concentration ratio was 1:15.5, but in muscles, liver and kidneys it was much lower: 1:0.79, 1:0.14 and 1:1.53 respectively. The absolute TMP and SDZ tissue concentrations 1 day after the last multiple dose administration were very low (maximum TMP: 0.29 μg/g in liver; maximum SDZ: 0.23 μg/g in kidneys). Neither drug was detected in any tissue 8 days after the last administration of TMP/SDZ. Based on our results, it was concluded that there is no support for the TMP:SDZ pharmaceutical ratio 1:5 in oral formulations of these compounds for pigs. The administration of oral TMP/SDZ formulations once a day may result in the absolute tissue concentrations of these drugs being too low for antibacterial activity. The withdrawal period for such an oral TMP/SDZ formulation for pigs (according to accepted guidelines in Europe for MRL of TMP<0.05 mg/kg of tissue) should not be less th

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00078.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The disposition of five therapeutic antimicrobial agents was studied in llamas (Lama glama) following intravenous bolus administration. Six llamas were each given ampicillin, tobramycin, trimethoprim, sulfamethoxazole, enrofloxacin and ceftiofur at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg, 15 mg/kg, 5 mg/kg, and 2.2 mg/kg of body weight, respectively, with a wash out period of at least 3 days between treatments. Plasma concentrations of these antimicrobial agents over 12 h following i.v. bolus dosing were determined by reverse phase HPLC. Disposition of the five antimicrobial agents was described by a two compartment open model with elimination from the central compartment, and also by non‐compartmental methods. From compartmental analysis, the elimination rate constant, half‐life, and apparent volume of distribution in the central compartment were determined. Statistical moment theory was used to determine noncompartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at stead state. Based on the disposition parameters determined, and stated assumptions of likely effective minimum inhibitory concentrations (MIC) a dose and dosing interval for each of five antimicrobial agents were suggested as 6 mg/kg every 12 h for ampicillin; 4 mg/kg once a day or 0.75 mg/kg every 8 h for tobramycin; 3.0 mg/kg/15 mg/kg every 12 h for trimethoprim/sulfamethoxazole; 5 mg/kg every 12 h for enrofloxacin; and 2.2 mg/kg every 12 h for ceftiofur sodium for llamas. Steady‐state peak and trough plasma concentrations were also predicted for the drugs in this study for l

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00079.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12 000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 μg/mL, reached at 1.7 h, and 1.3 μg/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 μg/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration ofStreptococcus zooepidemicusfor the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respective

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00080.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Tissue chambers, implanted subcutaneously in ponies, were inoculated withStreptococcus 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.

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00081.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

This study examined the pharmacokinetics of steady‐state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross‐over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2‐week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone concentration determination by high‐performance liquid chromatography. All gentamicin data were best approximated by a two‐compartment open model using sequential, weighted non‐linear regression. Pharmacokinetic parameters were calculated using model‐dependent formulae. Phenylbutazone data were analysed by non‐compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment from peripheral tissues (k21) (P<0.05) and there was a trend to a 24% increase in k12(P = 0.052). The gentamicin elimination half‐life was decreased 23% and the Vd(area)was reduced by 26%. No induction by gentamicin of changes in phenylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of distribution and elimination of gentamicin. Therefore, care should be exercised in the use of aminoglycosides in equine patients concurrently maintained

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00082.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The antimicrobial drug flumequine was given intravascularly and orally to cannulated and non‐cannulated Atlantic salmon (Salmo salar) in sea water at 11°. The cannulated fish were divided into two groups, which were given flumequine (25 mg/kg) intravenously into the caudal vein (n = 8) and orally via a stomach tube down the oesophagus (n= 8). After a washout period of 2 days, the intravenously administered fish were given the drug orally, and the orally administered fish were given the drug intravenously. Blood samples were taken at different time points after drug administration through a cannula inserted into the dorsal aorta. The fish in the non‐cannulated group were either given flumequine intravenously or orally, and blood samples were collected by killing five fish at predetermined time points after administration. The haematocrit values were measured in all the fish daily for 4 days after drug administration and thereafter, in all the collected blood samples throughout the whole experiment. The haematocrit values differed significantly between the cannulated and the non‐cannulated fish. We found low haematocrit values and slow drug elimination in the cannulated groups, compared with higher haematocrit values and faster drug elimination in the non‐cannulated groups, but further investigations are needed to prove any causal relations of this observation. The volume of distribution (Vd(ss)) was twice as large in the cannulated groups compared with the non‐cannulated group, in the fish administered the drug intravenously. In the last part of the elimination phase, the half‐lives differed considerably between the cannulated and the noncannulated groups both after oral and intravenous administration. The slower depletion of the drug concentration in the plasma of the cannulated fish is due to the largeVd(ss)as there are only small differences in clearance (ClT) between the groups. In this study the elimination of flumequine in cannulated Atlantic salmon differed from the elimination of flumequine in non‐cannulated A

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00083.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non‐steroidal anti‐inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three‐period cross‐over study using a tissue cage model of inflammation. For both S(+)‐ and R(‐)‐KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degree, transudate than for plasma. Unidirectional chiral inversion of R(‐)‐ to S(+)‐KTP was demonstrated. Administration of both enantiomers produced marked, time‐dependent inhibition of synthesis of serum thromboxane B2and exudate prostaglandin E2, indicating non‐selective inhibition of cyclo‐oxygenase (COX) isoenzymes COX‐1 and COX‐2 respectively. Administration of both enantiomers also produced partial inhibition of β‐glucuronidase release into inflammatory exudate and of bradykinin‐induced skin oedema. It is suggested that, although S(+)‐KTP is generally regarded as the eutomer, R(‐)‐KTP was probably at least as active in inhibiting bradykinin swelling. Pharmacokinetic/pharmaco dynamic (PK/PD) modelling of the data could not be undertaken following R(‐)‐KTP administration because of chiral inversion to S(+)‐KTP. but pharmacodynamic parameters,Emax, EC50,N,keo andt1/2(keO), were determined for S(+)‐KTP using the sigmoidalEmaxequation. PK/DP modelling provided a novel means of comparing and quantifying several biological effects of K

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00084.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n= 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n= 5) or 4.4 mg/kg (n= 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases (P<0.05) in total body clearance (CLB; 29.2 ± 3.9 vs. 43.8 ± 8.1 mL/ h‐kg) and the volume of distribution, calculated by area (Vd(area); 0.18 ± 0.05 vs. 0.25 ± 0.03 L/kg) or at steady‐state (Vd(SS); 0.17±0.04 vs. 0.25 ± 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly (P<0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00085.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY