摘要:

The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram‐negative bacteria, mycoplasma, and some grampositive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid‐mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight‐bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep‐seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00001.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Sodium meclofenamate is a non‐steroidal anti‐inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half‐lives of the drug were 7.2 min and 542 min respectively, Vsswas 1.68 L/kg and ClBwas 2.47 mL/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed (tmax‐212‐15 min,Cmax‐13.30‐24.01 μg/mL; andtmax‐2′, 52.50‐75 min,Cmax

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00002.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The ectoparasiticide amitraz stimulates α2,‐adrenoceptors to produce side‐effects such as bradycardia and hypotension. The actions of amitraz on baroreceptor reflex responses were evaluated in mongrel dogs by occlusion of both carotid arteries for 30‐s periods. Incremental doses of amitraz given intravenously showed that doses of 60 μg/kg and above significantly depressed pressor responses to carotid occlusion. By comparison, 2 μg/kg amitraz given by intracisterna magna (i.c.m.) injection significantly depressed both blood pressure and heart rate responses. Pretreatment of dogs with i.c.m. yohimbine (30 μg/kg) prevented the depressant effects of amitraz on the reflex, but prazosin (20 μg/kg), in separate experiments, had

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Oxcarbazepine has been proven to be a promising new antiepileptic drug for the treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively metabolized in humans, and therefore causes almost no induction of hepatic enzymes at clinically effective dosages. Though showing similar efficacy to carbamazepine, it has been reported to cause significantly fewer side‐effects. It was the purpose of the present study to determine whether oxcarbazepine might be suitable for the treatment of canine epilepsy. In single‐dose experiments, 40 mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric tube. Plasma concentrations reached peak concentrations of 2.4‐8.8 μg/mL at about 1.5 h and declined with an elimination half‐life of approximately 4 h. The corresponding concentrations of its metabolite, 10.11‐dihydro‐10‐hydroxycarbamazepine, did not exceed 1 μg/mL. During continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally in capsules to two dogs three times a day. Plasma concentrations showed a pronounced decline from day 3. and the terminal half‐life decreased to 2 h and 1 h. This is considered to be the result of oxcarbazepine inducing its own metabolism. The data reveal that oxcarbazepine, compared with former results with carbamazepine, offers no advantage for the treatment

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one‐day‐old Holstein bull calves (33‐53 kg body weight initially; Group 1) and 14 six‐month‐old Holstein steers (217‐276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughage/concentrate diet as Group 2. Groups 1‐IV and 2‐IV received ceftiofur sodium IV, and Groups 1‐IM and 2‐IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. Cmaxvalues were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 μg ceftiofur free acid equivalents/mL for 72 h in 7‐day‐old calves, but were less than 0.150 μg/mL within 48 h following IV or IM injection for 6‐ and 9‐month‐old calves. Intramuscular bioavailability, assessed by comparing the model‐derived area under the curve (AUCmod) from IM and IV injection at each age, appeared to be complete. After IV administration, theAUCmodin 7‐day‐old and 1‐month‐old calves (126.92±21.1 μg‐h/mL and 135.0±21.6 μg.h/mL, respectively) was significantly larger than in 3‐, 6‐ and 9‐month‐old calves (74.0±10.7 μg.h/mL, 61.0±17.7 μg.h/mL and 68.5±12.8 μg.h/mL, respectively;P<0.0001). TheVd(ss)decreased linearly within the first 3 months of life in cattle (0.345±0.0616 L/kg, 0.335±0.919 L/kg and 0.284±0.0490 L/kg, respectively;P= 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. TheClbwas significantly smaller in 7‐day‐old and 1‐month‐old calves (0.0178±0.00325 L/h.kg and 0.0167±0.00310 L/h.kg, respectively) than in 3‐, 6‐ and 9‐month‐old calves (0.0303±0.0046 L/h.kg, 0.0398±0.0149 L/h.kg and 0.0330±0.00552 L/h.kg, respectively;P≦0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1‐2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above theMICfor bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that pe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00005.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase (t1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half‐life of absorption was 2.51 ± 0.72 min andt1/2(β)was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

This paper describes the use of subcutaneously‐placed tissue chambers as a sterile soft‐tissue inflammation model in Thoroughbred horses. Acute, nonimmune inflammation was initiated by injecting a sterile lambda carrageenan solution into a tissue chamber. This model was used to study the temporal changes in oxygen and carbon dioxide tensions, pH, bicarbonate, protein, albumin, prostaglandin E2(PGE2) and leukotriene B4(LTB4) concentrations, cell counts and differential counts in tissue fluid from inflamed tissue chambers and control chambers. Skin temperatures over control and inflamed chambers were also compared. Carrageenan‐induced inflammation resulted in significant increases in tissue‐fluid carbon dioxide tension, leucocyte count, albumin, and PGE2and LTB4concentrations. It also resulted in a significant decrease in tissue fluid pH and HCO3‐ concentration. Inflammation did not result in significant changes in tissue‐fluid protein concentration, differential cell counts or skin temperature over the chambers. The use of this type of tissue chamber is wellsuited for studying the pathophysiology of a self‐contained, non‐immune inflammatory process. The model described in this paper could prove to be very useful in studies of the distribution of anti‐inflammatory drugs and the effects of such drugs on various aspects of the inf

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00007.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The pharmacokinetic properties and local tolerance of three oxytetracycline formulations, one conventional (Engemycine, 10%) and two long‐acting (Oxyter LA, 20% and Terramycin LA, 20%) were compared in clinically healthy cross‐bred pigs following intramuscular injection of single doses (20 mg/kg body weight) in the neck region. Non‐compartmental methods were used to calculate the pharmacokinetic parameters. Assessment of local tolerance was based on serum creatine phosphokinase (CPK) concentration and a combination of echographical, macroscopic and histological examinations of the intramuscular injection site. Statistically significant differences (one‐way analysis of variance,F‐test) were obtained between the three formulations in peak plasma concentration, peak time and mean residence time. Area under the curve did not differ significantly between the formulations. Using the Studentst‐test for paired data, the two long‐acting formulations differed significantly in peak plasma concentration and peak time. Both of the long‐acting formulations differed significantly from the conventional formulation in the peak time and mean residence time. All three formulations produced an increase in serum CPK concentrations. The increase in CPK concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6 to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional formulation). Echographical examination of the injection site showed lesions of an inflammatory type up to 96 h after IM injection of the drug products, whereas from 7 days the lesions represented primarily scar formation. Histological examination of tissue from the injection site did not correlate with echographical scores. The results obtained in this study show that the long‐acting formulations provide significantly longer mean residence times of oxytetracycline than the conventional formulation, and that local tolerance at the IM injection site was similar for all three formulations under the experimental conditions used in this study. It can be concluded that the longacting formulations provide the advantage of a longer dosage interval when administered to pigs by intramuscular injection in the neck region at a dose of 20

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00008.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three‐way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long‐term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h;ClB= 0.10 L/h.kg;Varea= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg,Cmaxof 1.4 μg/mL was reached attmaxof 2.5 h. MeanAUCandCmaxvalues had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, excepttmax(about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long‐term trial was 1.6, suggesting good tissue penetration of marbof

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00009.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The anti‐trichomonal efficacy and pharmacokinetics of dimetridazole were investigated in the homing pigeon(Columba livia). Dimetridazole was formulated for drinking water medication and as a prolonged‐release tablet. To suppress aTrichomonas gallinaeinfection successfully, medicated drinking water containing dimetridazole (400 mg/L) had to be administered for at least 3 days. A two‐day treatment with a dimetridazole tablet (20 mg/tablet) in fasted, as well as in fed, pigeons was shown to be ineffective. After intravenous administration of 20 mg dimetridazole, the drug plasma concentration‐time profile fitted a one‐compartment open model with a mean half‐life of 3.9 h. The absolute bioavailability of the tablet in fasted pigeons was 83.8%. The bioavailability of the tablet administered with food was reduced by 20%. Dimetridazole was rapidly metabolised to (1‐methyl‐5‐nitroimida

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00010.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY