Pharmacokinetics and bioavailability of ronidazole from a prolonged release tablet in the homing pigeon (Columba livid)

The pharmacokinetics of ronidazole and the bioavailability of a prolonged release tablet were studied in the homing pigeon. After intravenous administration of 5 mg ronidazole, the drug plasma concentration profile fitted a one-compartment open model. The mean half-life of the drug was 11 h and the volume of distribution was 0.86 l/kg. Total body clearance was 0.056 l/h/kg. A sustained release matrix tablet exhibited prolonged drug release in vitro. After oral administration of the matrix tablet to pigeons drug absorption was nearly complete. When given on an empty stomach, the tablet failed as a prolonged release system. Administration to previously fed pigeons resulted in an increase in tmax and a decrease in Cpmax.     

Oral chloramphenicol in dwarf goats-influence of vasopressin on its absorption and effect of diet on its biodegradation in ruminal fluid samples

The biodegradation of chloramphenicol was studied by incubating the drug (at concentrations of 72, 48 and 24 micrograms/ml) with ruminal fluid samples from dwarf goats fed two different diets. Biodegradation of the drug was much faster in samples from animals which were fed with hay and concentrate than in those obtained from goats which were fed grass pellets only. Recently, it has been suggested that lysine-vasopressin injected intravenously induces closure of the oesophageal groove in cattle and goats. Therefore, the influence of lysine-vasopressin on the oral absorption of chloramphenicol (50 mg/kg body wt) was studied in dwarf goats, using two formulations of chloramphenicol. The results suggest that vasopressin failed to induce this reflex mechanism. Furthermore, the shapes of the plasma concentration-time curves after oral administration of chloramphenicol palmitate and chloramphenicol dissolved in propylene glycol were markedly different. Possible mechanisms for the observed differences are discussed.     

Evaluation of antibiotics for racing pigeons (Columba livia var. domestica) available in The Netherlands

Antibiotics and chemotherapeutics marketed for use in racing pigeons (Columba livia var. domestica) were evaluated by comparing the dosages and indications given by the manufacturers with the data obtained by pharmacokinetic, bacteriological and efficacy studies. This comparison showed that only three of the recommended dosages and indications of the 60 formulations marketed in The Netherlands are scientifically sound and in accordance with the literature. It is to be expected that the majority of the antimicrobials for pigeons will not satisfy the requirements for final registration as a pigeon therapeutic under the Dutch Veterinary Medicines Act of 1985. Several factors affecting drug availability are discussed, such as the different routes of administration and the influence of food. The public health aspects of the consumption of medicated pigeons is also discussed. Although there is no legislation with regard to this subject, a recommended withdrawal time of 10 days for the majority of the antimicrobials seems advisable.     

Survey of the pathologic findings in a large production colony of pigeons, with special reference to pseudomembranous stomatitis and nephritis

Pathologic evaluations of pigeons dying between September 1984 and August 1985 are reported for a production colony of 1200-1800 White Carneau and Show Racer pigeons ranging in age from hatchlings to 12 years. Infectious diseases were the common causes of death in pigeons younger than 1 year; salmonellosis and nephritis were the common causes in pigeons 1-3 years old; and neoplasia and reproductive organ disorders were the common causes in pigeons older than 3 years. Monthly mortality was 2-4% in pigeons fed a cholesterol-containing diet and 0.9% in those fed noncholesterol-containing pellet diets. The increased deaths in the cholesterol-fed birds were attributed primarily to end-stage renal disease and atherosclerosis with secondary complications. The most frequently observed clinical entity in pigeons younger than 6 months was pseudomembrane formation on the oral and pharyngeal mucosa, termed pseudomembranous stomatitis. The definitive etiologic factor was not determined. Although all affected pigeons had similar gross lesions, the cases fell into one of three subsets, suggestive of bacterial, fungal, or viral etiologies. Chronic nephritis occurring as end-stage renal disease was more severe in pigeons fed a cholesterol-containing diet.     

Comparative in vitro characterization of moxidectin and doramectin percutaneous absorption through bovine skin

Topical formulations have achieved worldwide acceptance in veterinary medicine because their administration is an easy, less labor-intensive and nonstressing form. Any chemical compound that comes in contact with the skin has the potential to be locally and/or systemically absorbed. However, many factors related to the features of animal skin, composition of the topical formulation and to the drug itself can determine marked differences in the percutaneous absorption process. The aim of the current work was to characterize the pattern of in vitro percutaneous absorption for moxidectin (MXD) and doramectin (DRM), two of the most worldwide used topical macrocyclic lactone antiparasitic compounds in cattle. The work included the development of a simple and inexpensive in vitro assay useful to predict in vivo drug percutaneous absorption in cattle. Both drugs were administered as the commercial formulations intended for their topical administration to cattle. The in vitro studies were carried out using modified Franz-type vertical diffusion cells. Cattle skin slices of 500 μm thickness were prepared using a dermatome to separate the stratum corneum and upper epidermis from dermis and subcutaneous tissue. The receptor medium was sampled up to 72 h postadministration and drug concentrations were measured by HPLC. The parameters used to estimate the comparative in vitro skin permeation showed marked differences between DRM and MXD. A 5.29-fold longer lag time (T(lag)) was observed for DRM. Similarly, the flux (J) (2.93-fold) and the permeation coefficients (K(p) ) (2.95-fold) in cattle skin were significantly higher (P < 0.05) for DRM compared to those obtained for MXD. Additionally, the data obtained from the in vitro permeation studies was correlated with the plasma concentrations of both compounds achieved in vivo in cattle treated with the same topical formulations. Correlation coefficients between percentage of drug permeated in vitro vs. percentage of drug absorbed in vivo (up to 48 h post-treatment) were 0.856-0.887 (MXD) and 0.976-0.990 (DRM). However, the highest in vitro-in vivo correlations for both molecules were observed up to 24 h post-treatment A rapid screening method for testing different topical formulations can be achieved with the simple in vitro cattle skin permeation technique described here, which has been successfully adapted to test the comparative percutaneous absorption of MXD and DRM.     

Pharmacokinetics and anti-trichomonal efficacy of a dimetridazole tablet and water-soluble powder in homing pigeons (Columb a livia)

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 a Trichomonas gallinae infection 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-nitroimidazol-2-yl)methanol.     

Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine

Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements.     

Prolonged-release hard gelatin capsules of furosemide for the treatment of dogs

The object of this study was to examine whether prolonged-release hard gelatin capsule formulations could be developed for dogs. Different viscosity grades of hydroxypropyl methylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used to control drug release. Furosemide was chosen because of its wide use in the management of heart failure in dogs. In vitro , selecting different viscosity grades allowed good control of drug release, whereas in vivo the difference between formulations was clearly smaller. Although all formulations gave prolonged release, both inter- and intra-individual variation in the plasma concentration-time curves was high. It is difficult to develop prolonged-release formulations for drugs such as furosemide with highly variable pharmacokinetic properties. However, hard gelatin capsules containing hydrophilic polymers could still be a suitable choice for some drugs.     

A study of the influence of the method of oral administration of ampicillin upon plasma drug levels in calves.

Ampicillin was given orally to five Holstein calves using the following four different methods of administration: via stomach tube, mixed and fed in the calf starter ration, dissolved in milk and pail fed and administered orally as 400 mg commercial calf tablets. In addition, ampicillin was dissolved in milk and pail fed 20 to 30 minutes following intramuscular atropine. Ampicillin was only detected in the plasma of calves which had received the drug, pail fed in milk. Atropine administration slowed the appearance of the drug in the plasma but did not decrease the efficiency of absorption.     

同一蛋白质水平不同料型对肉种鸽生产性能的影响

试验旨在研究同一蛋白质水平(粗蛋白质为13%)不同料型对肉种鸽生产性能的影响。采用单因子试验设计,选用144对种鸽,随机分为4组,每组36个重复,每个重复1对种鸽。Ⅰ组饲喂柱状颗粒全价料,Ⅱ组饲喂球形颗粒全价料,Ⅲ组饲喂50%原粮和50%柱状颗粒料,Ⅳ组饲喂原粮和保健砂。预试期14 d,正试期106 d。结果显示:①整个试验期内,Ⅰ、Ⅱ组平均日耗料量均极显著低于其他2组(P<0.01),15~21日龄阶段Ⅲ组乳鸽平均日耗料量也极显著低于Ⅳ组(P<0.01);②Ⅰ、Ⅱ组均能使种鸽在繁殖期间体重极显著增加(P<0.01),但公鸽的增重比母鸽多;③乳鸽7日龄时,Ⅱ、Ⅲ组体重极显著高于Ⅳ组(P<0.01),但乳鸽14日龄时,这种显著差异消失;④Ⅰ组种蛋受精率极显著高于Ⅳ组(P<0.01),显著高于Ⅱ组(P<0.05),其余各组之间差异不显著(P>0.05)。提示,料型对种鸽生产性能有显著影响,但对啄羽现象无明显影响;建议在养鸽生产中推广柱状颗粒全价料型。     

Evaluation of the effects of intramuscular injection volume on midazolam-butorphanol induced sedation in domestic pigeons (Columba livia)

BackgroundCombinations of midazolam and butorphanol are commonly used in avian sedation protocols but no studies have been performed in Columbiformes. Minimizing intramuscular drug injection volumes is desirable, in order to reduce the potential for injection-induced discomfort. Reduction of drug injection volumes can be achieved by using higher concentrated drug formulations. The goals of this study were to evaluate a midazolam-butorphanol sedation protocol in domestic pigeons and to evaluate if a difference in total drug injection volume has an effect on sedation parameters in this species.MethodsTwelve adult pigeons were sedated with butorphanol (2 mg/kg) combined with 4 mg/kg of midazolam as either a standard (5 mg/mL) or concentrated (50 mg/mL) formulation, intramuscularly, in a randomized, blinded, complete cross-over study. Various parameters were used to assess for differences in sedation onset, depth, and recovery. Flumazenil (0.05 mg/kg) was administered intramuscularly for reversal of midazolam 30 minutes after sedative administration.ResultsThe sedation protocol resulted in moderate sedation and all birds became sternally recumbent, while 4of 12 birds lost righting reflex. Recovery was rapid in all birds following administration of flumazenil and no adverse reactions were observed. Significant differences in drug injection volumes had no clinically relevant effects on sedation parameters.Conclusions and clinical relevanceUse of concentrated midazolam resulted in ∼3.5 times smaller total injection volumes, while achieving the same efficacy as standard concentration of midazolam. The reduced injection volumes are desirable from an animal welfare standpoint, as they may reduce the risk of local discomfort associated with intramuscular injections.     

Toxicity in utility pigeons caused by the coccidiostat dinitolmide

Utility pigeons on 3 farms were affected by a severe neurological disturbance manifested by fine tremors, rolling gait and incoordination. Affected birds had necrosis of the Purkinje cells of the cerebellar cortex. The birds from the 3 farms had been fed a pelleted diet obtained from a single mix of feed prepared by a stockfeed manufacturer. When feed obtained from the farms was given to utility pigeons under controlled conditions at the laboratory, they suffered the same clinical signs and lesions as seen in birds from the farms. Cross-bred cockerels were not affected when given this feed from day-old to 6 weeks of age. Samples of the feed contained 185 to 226 ppm of the coccidiostat dinitolmide. Utility pigeons given a prepared diet containing a similar level (234 ppm) of dinitolmide developed an identical condition after 3 to 4 weeks feeding. Laying hens were not affected by this feed. Dimetridazole, which was also present in some of the original feed samples, did not exacerbate the condition when included in the diet at a rate of 233 ppm. Production of squabs from the affected farms was dramatically reduced, and many of the breeder had to be culled because of the long-standing neurological disease.     

不同日龄乳鸽肠道CaBP-D28k基因表达的变化规律研究

为了解乳鸽肠道钙吸收规律,以满足乳鸽生产中钙的营养需要,试验将48对健康种鸽随机分为8个重复,每个重复6对,产蛋后由种鸽自然孵化和哺育乳鸽,在乳鸽7、14、21、28日龄时称量体重,平均体重分别为(120.27±31.37)g、(264.35±88.77)g、(399.22±75.04)g和(454.16±38.39)...     

Bioavailability and pharmacokinetics of ampicillin and amoxycillin from tablets, capsules and long-acting preparations in the homing pigeon (Columba livia)

Three ampicillin and three amoxycillin formulations (tablets and capsules, administered orally, and oily suspensions, injected intramuscularly (i.m.) and subcutaneously (s.c.] were studied in twenty adult homing pigeons (Columba livia). Bioavailability, pharmacokinetics and recovery were determined for each product and administration route. A standard dose of 50 mg/pigeon or 100 mg/kg was used in each study. The mean availability calculated for each of these preparations was 7% for ampicillin anhydrate tablets, 22% for amoxycillin trihydrate tablets, 17% for ampicillin trihydrate capsules, 67% for amoxycillin trihydrate capsules, 46% for ampicillin oily suspension i.m., 67% for amoxycillin oily suspension i.m. and 43% for amoxycillin oily suspension s.c. The blood concentration-time curves for the tablets were very scattered, which was far less the case for the capsules. The maximum blood concentration (Cmax) for amoxycillin was twice as high as for ampicillin. The Cmax resulting from the oily suspensions administered i.m. were low (4.35 +/- 1.05 and 5.04 +/- 1.36 mg/l, for ampicillin and amoxycillin, respectively). The Tmax for ampicillin was 10 h and for amoxycillin it was 0.9 h after administration. Both curves showed biphasic absorption, the initial peak representing an absorption and a distribution phase and the second part reflecting the 'depot-nature' of the drug. After the s.c. administration of the amoxycillin oily suspension the same pattern was found, but the Cmax, which was found at 2.13 +/- 1.03 h after administration, was low (2.81 +/- 0.68 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of pp'‐DDT on the rate,amplitude and weight of the heart of the pigeon and Bengalese finch

Fifty‐four homing pigeons were fed control diets and dose rates of pp'‐DDT ranging from 3 to 36 mg/kg d. At 3 mg/kg d there was an increase in the pulse rate and S wave amplitude after 3 weeks dosing followed by an increase in the heart weight. The pulse rate, amplitude and weight then decreased with increasing dose rate. At high dose rates the heart was flaccid and reduced to half the normal weight after 8 weeks. This pattern of results is similar to that obtained for oxygen consumption, body temperature and vitamin A storage, using this species. This suggests that DDT causes hyperthyroidism at low dose rates and hypothyroidism at high dose rates in pigeons. These results contrast with those for the Bengalese finch which suggest hyperthyroidism only. The possible mechanisms and effects of these reactions are discussed.     

1株信鸽源鼠伤寒沙门氏菌的分离鉴定及其耐药性和毒力分析

本试验旨在鉴定临床疑似沙门氏菌感染致死信鸽的病原菌并确定致病菌的耐药及毒力状况。通过细菌分离培养、菌落形态观察、染色镜检、生化鉴定、血清分型、16S rRNA基因测序分析和康复信鸽血清平板凝集试验进行鉴定,并通过药敏试验、耐药基因和毒力基因检测进行耐药性和毒力分析。结果显示,分离纯化的细菌在BS、XLD、HE培养基上为黑色菌落,镜检为无荚膜、无芽孢的革兰氏阴性短杆菌;分离菌株生化反应结果符合沙门氏菌生化特性;分离菌株血清型为1,4,12：i：1,2;分离菌株16S rRNA基因序列系统进化树分析显示,该分离菌株与鼠伤寒沙门氏菌聚为一支,同源性>99%,康复信鸽血清与分离菌株发生特异性凝集,结合生化反应和血清分型结果该菌株鉴定为鼠伤寒沙门氏菌;分离菌株对氟苯尼考耐药,经耐药基因检测携带floR、cmlA氯霉素类耐药基因,与耐药表型相符;分离菌株mogA等17种毒力基因检测均为阳性。本试验成功分离到1株信鸽源鼠伤寒沙门氏菌,分离菌株对氟苯尼考耐药且具有较强毒力,为下一步信鸽沙门氏菌的防治和研究提供了参考依据。     

Bioequivalence of ivermectin formulations in pigs and cattle

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.     

Pharmacokinetic evaluation of four ivermectin generic formulations in calves

The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (IVM G1-G4) were compared after their subcutaneous (SC) administration to healthy calves. The disposition of other avermectin-type endectocide compounds, doramectin (DRM) and abamectin (ABM), was also assessed in the same pharmacokinetic trial. Forty-two parasite-free Aberdeen Angus male calves were randomly allocated into six treatment groups. Animals in each group (n = 7) received SC treatment (200 microg/kg) with one of the commercially available endectocide formulation used in the trial. Blood samples were taken into heparinised vacutainer tubes from the jugular vein prior to and up to 35 days post-treatment. The recovered plasma was analysed by HPLC with fluorescence detection. Large kinetic differences were observed among the DRM, ABM and IVM formulations under evaluation. The DRM plasma concentration profiles were higher than those measured for ABM and all the IVM generic formulations. The higher and sustained plasma concentrations of DRM accounted for greater area under concentration-time curve (AUC) and longer mean residence time (MRT) values compared to those obtained for both ABM and the IVM generic preparations. The pattern of IVM absorption from the site of subcutaneous administration showed differences among the generic formulations under evaluation. The IVM G2 preparation showed higher peak plasma concentration and AUC values (P < 0.05) compared to those obtained after the administration of the IVM G1 formulation. Longer (P < 0.05) MRT values were obtained after the administration of the IVM G3 compared to other IVM generic preparations. The kinetic behaviour of ABM did not show significant differences with that described for most of the IVM formulations. This study demonstrates that major differences on drug kinetic behaviour may be observed when using different endectocide injectable formulations in cattle.     

A study of the pharmacokinetics and tissue residues of an oral trimethoprim/sulphadiazine formulation in healthy pigs

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 than 5 days.     

肉鸽大肠杆菌的分离与鉴定

为研究肉鸽大肠杆菌的生化特性、药敏情况、血清型和致病性。2010年1月江苏省某肉鸽场鸽群出现呼吸困难,死亡增多现象。对病死鸽剖检发现,以气囊炎和肺部坏死为主,无菌采集病料分离到1株细菌,经分离培养、染色镜检、生化特性鉴定,确定为大肠杆菌,微量凝集试验表明其血清型为O2。经过肺结节压片镜检,没有发现霉菌的菌丝;检测健康鸽和患病鸽各10只的鸽新城疫抗体,发现其抗体效价比较高且整齐度较好,两者之间的抗体无明显差异。对分离菌株进行药敏试验,结果表明对恩诺沙星等7种药物敏感,对阿莫西林等16种药物已产生了耐药性。将分离到的菌株接种21日龄雏鸽进行动物回归试验,死亡率达80%,说明该分离菌株对雏鸽具有较强的致病性。