摘要:

Tinidazole 15 mg/kg was administered to eight Beagle dogs with gingivitis or periodontitis twice daily for 3 days. Tinidazole concentrations in blood and gingival crevicular fluid (GCF) were measured 1,3,6 and 9 h after the morning dose each day. The concentration of tinidazole was determined by high performance liquid chromatography (HPLC). The mean concentration of tinidazole in GCF for each dog ranged from 6.05 to 9.32 αg/mL at different time points after the first dose, and on the first day the highest concentration was observed 6 h after the drug administration. Tinidazole concentrations were 34 ± 4%‐72 ± 9% (mean ± SEM) of simultaneous plasma concentration. At steady‐state, on the third treatment day, the mean tinidazole concentrations in GCF ranged from 6.68 to 13.1 μg/mL, i.e. 44 ± 6%‐75 ± 25% of the corresponding concentrations in plasma. Tinidazole concentration in GCF exceeded the MIC values for putative path‐ogenic periodontal bacteria and it is concluded that, when indicated, tinidazole could be used for chemotherapy of periodo

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00035.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Protein binding kinetics of basic antimicrobials including trimethoprim (TMP), erythromycin (EM), lincomycin (LM) and clindamycin (CM) were studied using porcine plasma, albumin and æ‐acid glycoprotein (AGP). Rosenthal plots of these basic drugs in porcine plasma suggest saturable and non‐saturable binding. Dissociation constants (Kd) and binding capacity (Bmax) for saturable binding were as follows: TMP,Kd= 8.58 μmol/L, Bmax= 5.26 μmol/L; EM,kd= 2.72 μmol/L, Bmax= 3.06 μmol/L; LM,kd= 3.96 μmol/L, Bmax= 6.58 μmol/L and CM,kd= 4.43 μmol/L, Bmax= 21.7 μmol/L. The proportionality constants (Bmax2/kd2) for non‐saturable binding were 0.29 in TMP, 0.52 in EM, 0.17 in LM and 3.2 in CM. Thekds of the drugs in porcine AGP solution were determined by a fluorescence quenching method, using 1‐anilino‐8‐naphthalene sulphonate (ANS) as a fluorescent probe: 9.51 μmol/L in TMP, 1.89 μmol/ L in EM, 4.48 μmol/L in LM and 9.69 μmol/L, in CM. Comparable kd values between porcine plasma and AGP solution indicated that AGP is a major saturable binder in porcine plasma. Binding property to porcine albumin presented linearity, showing the following proportionality constants: 0.23 in TMP, 0.38 in EM, 0.01 in LM and 0.76 in CM. The comparable proportionality constants of TMP and EM between porcine plasma and albumin solution indicate that albumin is a major non‐saturable binder, whereas proportionality constants of LM and CM in albumin solution compared to those in porcine plasma were low, implying another non‐saturable binder, i.e. lipoprotein. Simulation curve of drug‐binding percentage vs. AGP concentrations showed that in pigs under a pathologic state, or during early growth stage with high AGP levels, AGP could be a main contributor to drug‐plasma protein binding for all drugs examined. The increase of AGP from normal to pathological concentrations induced a decrease in the unbound fraction: LM>CM>EM>TMP in order of AGP contribution to drug binding. Therefore, the disposition and efficacy of basic antimicrobials which bind to AGP with high affinity could be markedly influenced by altered AGP levels, implying AGP contribution to pharm

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00036.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The choice of antibacterial drugs for the treatment of bacterial diseases in farmed salmonids changed dramatically during the period 1980‐1994. In terms of treatment doses, oxytetracycline chloride was the most frequently prescribed antibacterial drug during the periods 1980‐1983 and 1985‐1986. In 1984, prescriptions changed in favour of furazolidone and trimethoprim/ sulphadiazine (1:5). Oxolinic acid was introduced for use in farmed fish in Norway in 1987, and immediately became the drug of choice, comprising 36% and 50% of the prescribed treatment doses in 1987 and 1988, respectively. In 1989, flumequine was temporarily approved for use in farmed salmonids, and during the period 1989‐1994 antibacterial drug therapy in farmed salmonids acquired the character of a‘mono‐therapy’with the quinolones flumequine and oxolinic acid. This rapid change‐over in the choice of drug may partly be explained by the development of bacterial drug resistance in farmed salmonids, both to oxytetracycline and trimethoprim/sulphadiazine. The prescribing of furazolidone declined to zero during the study period. The morbidity caused by bacterial infections was defined as the number of treatment doses of antibacterial drugs per kg biomass of farmed salmonids per year. It was estimated that during the period 1988‐1995, an average of 39% (mean value) of farmed salmon received, in theory, an antibacterial cure once each year. In comparison, the corresponding figure for the period 1981‐1988 was 60%. However, in 1993 this figure fell to 13%, and declined even further in 1994 to 2.3%. The practice of on‐farm mixing of medicated feed, using prescribed raw materials (pure drug substances) or premix formulations, declined significantly during the period 1992‐1994. This was due to the introduction, in 1992, of new regulations on the prescribing

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00037.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Twelve mixed‐breed swine (26.5‐42.5 kg) received three daily intramuscular (i.m.) doses of14C‐ceftiofur hydrochloride. Three males and three females, received 6.76 ± 0.83 mg of14C‐ceftiofur free acid equivalents (CFAE)/kg body weight (b.w.)/day, while the other group received 4.41 ± 0.97 mg‐CFAE/kg b.w./day. The swine were slaughtered 12 h following the last dose. Total dose accountability for the 6.76 mg dose was 91.44 ± 16.11% (72.51% in urine; 12.63% in faeces). For the 4.41 mg dose, accountability was 100.35 ± 20.45% (82.48% in urine; 12.85% in faeces). Within the tissues used for residue monitoring, the highest concentrations were observed in the kidneys (10.68 and 6.33 μg‐CFAE/g for the 6.76 and 4.41 mg doses, respectively), followed by the injection sites, lungs, liver and muscle. In a separate study, twelve mixbreed swine (23.1‐39.7 kg) received14C‐ceftiofur hydrochloride at 3.08 mg‐CFAE/kg b.w. once daily for 3 days. Two males and two females were slaughtered at either 12, 72 or 120 h after the last dose. Total dose accountability for the 3.08 mg dose was>83% (>68% in urine;>13% in faeces). In swine slaughtered 12 h after the last dose, residue concentrations closest to the safe concentrations were observed in the kidneys (3.62 μg‐CFAE/ g), followed by the injection sites

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00038.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration‐time profiles, following i.v. (25 mg/kg) dosing were best described by a 2‐compartment model. After intravenous administration, the volume of distribution at steady‐state (Vd(ss)), the total systemic clearance (ClB), the elimination half‐life (t1/2p) and theMRTwere 0.303 L/kg, 482.3 ml/h‐kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, thetmaxandCmaxwere 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, thetmaxandCmaxwere 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different dis

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00039.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short‐lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administratio

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00040.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The effects of intravenous administration of variable‐dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (<2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly greater proportion of cats which received ketamine and midazolam 0.5 mg/kg or above did not swallow in response to a finger or a laryngoscope placed in the mouth compared with that which received ketamine alone. The length of time in which cats did not swallow was only significantly longer at midazolam doses of 1.0 mg/kg and above. At midazolam doses of 0.5 mg/kg or above, the proportion of cats without a nociceptive response to a tail or paw clamp was significantly greater than cats which received ketamine alone. The time period without nociceptive response, however, was not influenced by midazolam administration. The time taken for cats which received ketamine and midazolam 0.05 mg/kg or 0.5 mg/kg to assume sternal position, walk with ataxia, walk without ataxia, behave normally when approached or restrained and recover normal arousal state was not significantly different from cats which received ketamine alone. Ketamine and midazolam 5.0 mg/kg significantly prolonged all recovery times compared with ketamine alone. Unfortunately, a greater proportion of cats which received ketamine and midazolam 0.5 or 5.0 mg/kg exhibited detrimental behavioural effects. These were more likely to be adverse and included restlessness, vocalization and difficulty approaching and restraining cats. In this study,

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00041.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Tilmicosin(TM), a macrolide antibiotic and active ingredient in formulated Micotil 300TM(Eli Lilly and Co., Indianapolis, IN, USA), is the active ingredient in a formulated animal product used for the treatment of respiratory tract infections in cattle. Owing to the concern of governmental regulatory agencies over the possibility of an accidental injection of the antibiotic to a livestock handler, the cardiovascular effects of sub lethal doses of TM were evaluated in conscious mixed‐breed dogs. Left ventricular function, systemic arterial blood pressure, and heart rate (HR) responses to TM alone and in combination with propranolol(P) or dobutamine HCl(DOB) were evaluated. Dogs were instrumented with indwelling micromanometers implanted in the left ventricular chamber and in the thoracic aorta. Cardiovascular variables were recorded, and the peak value of the first derivative of left ventricular pressure (dp/dt(max)) was used as an index of left ventricular inotropic state. Six treatments were randomly assigned to each of the six dogs using a Latin square design. The six treatments were vehicle, TM alone (2.5 mg/kg of body weight), TM immediately followed by P. and TM immediately followed by 1 of 3 dosages of DOB infused for ≅45 min. Additionally, doses of TM alone (0.25, 1.0, 2.5, and 5.0 mg/kg) were administered to complete a dose‐response curve. TM caused dose dependent decreases in (dp/dt(max)) and aortic pulse pressure. HR increased dose‐dependently. Left ventricular end‐diastolic pressure increased at the 2.5 and 5.0 mg/kg dosages. Left ventricular systolic pressure was reduced dose‐dependently at the 2.5 and 5.0 mg/kg dosages. Treatment with P exacerbated the negative inotropic effect and the decrease in left ventricular systolic pressure, but did not attenuate the tachycardia associated with TM treatment. DOB attenuated the changes in ventricular inotropic state in a dose‐dependent manner. DOB infusion also restored left ventricular systolic pressure at dosages of 3 or 10 μg/min/kg. Our data indicate that toxic doses of TM may have a negative inotropic effect in conscious dogs. HR increased in a dose‐dependent manner and was not the result of β1‐receptor stimulation. DOB reversed some, but not all, of the effects caused b

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00042.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Antigen challenge involving exposure to straw and mouldy hay for 7 h produced lung function changes and neutrophil recruitment to the lungs in horses with chronic obstructive pulmonary disease (COPD). During the challenge, an increase in radiolabelled neutrophils in the lungs occurred, together with increased respiratory rate and pleural pressure. The role of platelet activating factor (PAF) in antigen‐induced neutrophil accumulation, and increased pleural pressure and respiratory rate was investigated by administering the PAF receptor antagonist WEB 2086 to asymptomatic COPD horses prior to antigen challenge. WEB 2086 (3 mg/kg i.v.) did not affect antigen‐induced changes in either neutrophil accumulation or respiratory function. These results suggest that PAF may not be an important mediator of the response to antigen in equine C

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00043.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Paracetamol was administered at dosages of 5 mg/kg to camels and 10 mg/kg to goats by the intravenous and intramuscular routes. Parent paracetamol had a significantly slower clearance (21.9 ± 1.4 mL/min.kg vs. 52.8 ± 7.3 mL/min.kg) (P<0.01) in camels than in goats. In camels the predominant metabolite in plasma was the sulphate, although the ratios of glucuronide:paracetamol and sulphate:paracetamol were similar (5.20 ± 0.50 vs. 6.59 ± 0.51) following intravenous administration. In goats the glucuronide metabolite was the predominant moiety in plasma, and the area under the curve (AUC) of the sulphate was only 3.89% of that of the glucuronide conjugate. The apparent AUC for paracetamol in the camel following intramuscular administration was larger than that following intravenous administration, however, when the bioavailability (F) was determined, with correction for altered half‐life, within the animal and between study phases it was 71 ± 17% in goats and 105 ± 26% in

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1996.tb00044.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY