摘要:

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge withActinobacillus pleuropneumoniaetoxins. Endobronchial challenge withA.pleuropneumoniaetoxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half‐lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The meanAUCof TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin‐induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94–99%, 45–56% and 40–50%, respectively. Based on knowledge ofin vitroantimicrobial activity of the drug combinations againstA.pleuropneumoniaeit was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A.,pleuropneumoniaestrains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half‐lives of SMX and TMP in pigs this combination is preferred to the combination of S

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00588.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Flunixin meglumine (FM) was administered either orally as granules or intravenously to six heifers in a two period crossover study. Single doses of 2.2 mg/kg body weight were used. Pharmacokinetic variables were calculated using statistical moment methods. The effect exerted by flunixin was measured as changes in the basal plasma concentration of the main metabolite of prostaglandin (PG) F2α. After oral FM the arithmetic means of pharmacokinetic variables were:MRT= 12.7 h;MAT =6.3 h;Cmax= 0.9 μg/mL;tmax= 3.5 h. The bioavailability was 60% and the mean half‐life (harmonic mean) was 6.2 h. Oral administration of FM inhibited as effectively as intravenous administration the prostaglandin biosynthesis. The concentration of the PG metabolite decreased almost as rapidly as after intravenous administration. The duration of the effect was prolonged and the PG metabolite concentration was significantly lower between 10 and 30 h after oral than after intravenous administration. The results indicate that oral dosing of flunixin, in the form of granules, can be an alternative to intravenous administration for therapeutic use in cat

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00589.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200 000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13–18 groups (n= 5–10 individuals/group) of the dosed animals were killed at different post‐dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi‐exponential kinetic models were fitted to the observed tissue concentration‐time data by applying a non‐linear least‐squares regression computer program. Tissue half‐life, peak tissue concentration, and time of peak tissue concentration were determined. Half‐life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6–1.4, 4.7–9.0, 4.5–18.9, 1.8–3.1, 0.9–3.0, 3.4–9.6, 5.0–16.1 and 7.4–12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 μg/g in various tissues ranged from 5.0–11.6. 70.0–110.5. 114.0–179.8, 21.3–30.3,4.1–24.8 and 47.8–84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residu

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00590.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In this paper, the design and statistical analysis of field trials for the evaluation of the efficacy of clinical mastitis therapeutics is covered. First, general issues underlying the design of clinical trials are reviewed. These include bias and confounding; randomization and blocking; and study objectives and choice of the corresponding hypothesis. Specific issues in the design of clinical mastitis trials are also discussed. Selection of subjects is discussed with regard to choice of experimental units, identification of reference population and study population, inclusion and exclusion criteria, and sample size calculation. Next, a section on treatment administration and evaluation of cure reviews treatment, blinding, choice of response measure, as well as compliance, withdrawal, and early termination. The statistical analysis section addresses possible statistical models, treatment of confounding, and fixed vs. random effects. In conclusion, well‐conducted clinical mastitis trials represent an invaluable, albeit difficult and expensive, effort to evaluate efficacy and tolerance under usual circumstances of us

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00591.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Marbofloxacin is a new fluoroquinolone developed exclusively for veterinary use. Minimum inhibitory concentrations of marbofloxacin were assessed for 816 recent isolates associated with canine or feline diseases. Marbofloxacin showed a broad spectrum of activity against gram‐negative and gram‐positive bacteria. Invitrorates of killing of marbofloxacin and enrofloxacin were compared against strains ofStaphylococcus intermediusandPasteurella multocida, and the results showed no marked difference between the two antibiotics. The duration of bactericidal activity was evaluatedex vivoin the urine of dogs and cats treated with marbofloxacin and lasted from 2 to 5 days after a single administration according to the dosages. Post‐antibiotic effect durations were determined withEscherichia colt, PasteureUa multocida, Staphylococcus aureusandStaphylococcus intermediusand were found almost equal to those of enrofloxacin or ciprofloxacin. These results predict a great potential for marbofloxacin in the treatment of a wide range of diseases in dogs and

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00592.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration (Cmax), and areas under the concentration curve (AUC0–) were determined from plasma concentrations. Animals treated by the sc route showed a meanAUC0–of 457 ± 66 ng±day/mL (± SD) and a meanCmaxof 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a meanAUC0–of 475 ± 82 ng‐day/mL and a meanCmaxof 33.1 ± 9.0 ng/mL Absorption constants (ka) determined by modelling were 0.542 ± 0.336 day‐1after sc administration and 0.710 ± 0.357 day‐1after i.m. administration. The 90% confidence limits on the difference between meanAUC0–values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group.Cmaxwas somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In (Tmax+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulatio

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00593.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The disposition kinetics of tylosin tartrate administered intravenously (i.v.) at 10 mg/kg and intramuscularly (i.m.) at 20 mg/kg were studied in normal camels and in the same camels at the end of a 14 day water‐deprivation period. After i.v. treatment, serum tylosin concentrations in the water‐deprived camels were significantly higher, rate of drug elimination was slower, the volume of distribution was significantly smaller, and total body clearance was significantly slower than in the normal camels. On the other hand, serum drug concentrations were lower in the water deprived camels after i.m. dosing, the mean absorption time was significantly shorter and the i.m. availability was significantly smaller than in the normal camels. Water‐deprivation was thought to cause reduced rate of tylosin elimination by the liver, as was shown for antipyrine—a drug which is eliminated from the body exclusively by the liver. Redistribution of tylosin in tissues concomitant with a greater proportion of drug in blood and extracellular fluid of water‐deprived camels was suggested as a partial explanation for the higher serum drug levels seen after i.v. dosing. The low i.m. availability observed in the water‐deprived camels implies that i.v. is the route of choice for tylosin administration to ill, dehydr

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00594.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Channel catfish (n= 84) maintained at a water temperature of 27°C were used in a feeding study to determine the plasma to muscle concentration ratios of sulfadimethoxine (SDM) and 4‐N‐acetylsulfadimethoxine residues. Sulfadimethoxine medicated feed was provided free choice at 42 mg SDM/kg body weight once daily for 5 days and the plasma and muscle concentrations of SDM were determined at selected withdrawal times (6, 12, 24, 48, 72, and 96 hours) following the last dose. Considerable variation in total SDM tissue concentration among fish within a sampling period was observed. For fish (n= 12) at six hours post‐dose, total SDM concentrations ranged from 1.4–24.8 μg/mL and 0.6–12.6 μg/g, with mean total SDM concentrations of 9.1 μg/mL and 5.3 μg/g for plasma and muscle, respectively. However, a mean plasma:muscle concentration ratio of 1.8:1 ± 0.3:1 was obtained over all concentrations and sampling periods. The plasma:muscle 95%tdistribution interval for individual fish was 1.2:1 to 2.4:1. A correlation coefficient of 0.967 was obtained for the relationship between plasma and muscle total SDM concentration among individual fish (n= 25). Results of this study indicate that plasma total SDM concentration may be used to identify samples containing violative SDM muscle residue. No fish contained total SDM muscle residues greater than the FDA tolerance (0.1 μg/g) by 48 hours followin

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00595.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00596.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY