Pharmacokinetics of chlortetracycline potentiation with citric acid in the chicken

Serum concentrations of chlortetracycline (CTC) in healthy chickens were determined for the 24-hour period after they were given CTC (with and without citric acid) as an oral (25 mg/kg) or IV (0.9 mg/kg) dose. The oral time-course drug data were fitted adequately by a 2-compartment pharmacokinetic model with absorption. The resulting absorption rate constant (Ka) for the birds orally given CTC with citric acid was nearly equal to that for the birds given CTC alone. Although the uptake of orally administered CTC was rapid, only a small fraction of the dose was absorbed. The administration of citric acid-CTC significantly increased the mean serum concentration of CTC and the fraction of the dose absorbed. The citric acid-CTC mixture also produced significantly higher elimination (Kel) and distribution (K12) rate constants for CTC.     

饲用金霉素对肉仔鸡免疫系统生长发育及免疫反应的研究

试验用１日龄ＡＡ商品代肉用公雏５４０只,随机分成３组,每组１８０只,分成１２个重复（１５只／重复）,其中６个重复用作生产性能测定,另６个重复用于测定免疫学指标。在日粮中分别添加０（Ａ组）、５０（Ｂ组）、１５０ｍｇ／ｋｇ（Ｃ组）的金霉素（Ｃｈｌｏｒｔｅｔｒａｃｙｃｌｉｎｅ,ＣＴＣ）。试验表明：（１）在肉久日粮中添加１５０ｍｇ／ｋｇ ＣＴＣ,可以显著地提高肉伍鸡的增重速率和饲料转化效率（Ｐ〈０．０１）     

Performance and carcass merit of growing beef steers with chlortetracycline-modified sensitivity to pituitary releasing hormones and fed two dietary protein levels

This paper reports the effects of reduced sensitivity to growth hormone-releasing hormone and thyrotropin-releasing hormone through feeding a subtherapeutic level of chlortetracycline (CTC; 350 mg CTC/d) and two levels of dietary CP (10% and 13% of diet DM) on growth performance and carcass merit characteristics. Thirty-two steers (initial average BW, 286 kg) were adapted to a common 13% CP diet consisting primarily of grass hay, corn, and soybean meal fed to gain 1.25 kg/d. The steers were assigned to four treatments (with or without CTC and 10% or 13% dietary CP in a factorial arrangement) and fed ad libitum amounts of diet for 91 d. Feed intake was determined daily and steers were weighed weekly. Steers were killed at the end of the feeding period for carcass merit determinations. Efficiency of BW gain was greater (P < .05) for steers fed the 13% CP diet than for the 10% CP diet and tended to be less for CTC-steers when the 10% CP diet was fed and greater for the CTC-steers when the 13% CP diet was fed (CTC x dietary CP interaction, P < .10). Feeding CTC increased (P < .01) fat over the longissimus muscle and marbling. This study is interpreted to indicate that the sustained effect of subtherapeutic feeding of CTC to cattle appears to increase fat deposition consistent with a reduced growth hormone and thyroid status reported earlier for these same steers. This would tend to increase energy utilization but may not necessarily produce a measurable increase in BW gain.     

Gentamicin dosage in foals aged one month and three months

The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (3.3 +/- 0.8 h, n = 8) foals, and was independent of the dose. One-month-old foals did not appear to have a deficiency in renal excretion of gentamicin. The minimum inhibitory concentration of gentamicin for Corynebacterium equi and certain other equine bacterial isolates was less than 0.195 microgram/ml. It was concluded that 2 mg/kg bwt administered by im injection at 8 to 12 h intervals, depending on the severity of the infection, could be recommended as the dose rate for treatment of systemic infections caused by microorganisms that are susceptible to gentamicin.     

Effects of oral chlortetracycline and dietary protein level on plasma concentrations of growth hormone and thyroid hormones in beef steers before and after challenge with a combination of thyrotropin-releasing hormone and growth hormone-releasing hormone.

The objective of this study was to determine the effect of a subtherapeutic level of chlortetracycline (CTC) fed to growing beef steers under conditions of limited and adequate dietary protein on plasma concentrations of GH, thyroid-stimulating hormone (TSH), and thyroid hormones before and after an injection of thyrotropin-releasing hormone (TRH) + GHRH. Young beef steers (n = 32; average BW = 285 kg) were assigned to a 2x2 factorial arrangement of treatments of either a 10 or 13% crude protein diet (70% concentrate, 15% wheat straw, and 15% cottonseed hulls) and either a corn meal carrier or carrier + 350 mg of CTC daily top dressed on the diet. Steers were fed ad libitum amounts of diet for 56 d, and a jugular catheter was then placed in each steer in four groups (two steers from each treatment combination per group) during four consecutive days (one group per day). Each steer was injected via the jugular catheter with 1.0 microg/kg BW TRH + .1 microg/kg BW GHRH in 10 mL of saline at 0800. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 120, 240, and 360 min after releasing hormone injection. Plasma samples were analyzed for GH, TSH, thyroxine (T4), and triiodothyronine (T3). After 84 d on trial, the steers were slaughtered and the pituitary and samples of liver were collected and analyzed for 5'-deiodinase activity. Feeding CTC attenuated the GH response to releasing hormone challenge by 26% for both area under the response curve (P<.03) and peak response (P<.10). Likewise, CTC attenuated the TSH response to releasing hormone challenge for area under the response curve by 16% (P<.10) and peak response by 33% (P<.02), and attenuated the T4 response for area under the curve by 12% (P<.08) and peak response by 14% (P<.04). Type II deiodinase activity in the pituitary was 36% less (P<.02) in CTC-fed steers than in steers not fed CTC. The results of this study are interpreted to suggest that feeding subtherapeutic levels of CTC to young growing beef cattle attenuates the release of GH and TSH in response to pituitary releasing hormones, suggesting a mechanism by which CTC may influence tissue deposition in cattle.     

Transference of Dietary Veterinary Drugs into Eggs

Twelve veterinary drugs, bacitracin (BC), chloramphenicol (CAP),chlortetracycline (CTC), oxytetracycline (OTC), tylosin (TS), amprolium (APL), furazolidone (FZD), nicarbazine (NCZ), ormetoprium (OMP), sulfadimidine (SDD), sulfadimethoxine (SDM) and sulfamonomethoxine (SMM) were fed to laying hens for 14 days, each at a dietary concentration of 500 mg/kg. The concentrations of the drugs in the eggs from these birds were determined at 2-day intervals for 14 days after the start of feeding. The relationship between the concentrations of the drugs (mg/kg) in the eggs and the number of days after the start of feeding was analysed by regression and covariance analyses. The concentrations of the drugs in the eggs became constant after 4 days for OTC, TS, FZD and all the sulfonamides, and after 6 days for CAP, APL, NCZ and OMP. No BC or CTC was detected in the eggs. The transfer rates of the 10 drugs (excluding BC and CTC) from the feed to eggs varied from 0.005% for TS up to 1.540% for SDD.     

壳聚糖对肉仔鸡生长性能及血清生化指标的影响

试验选用1日龄AA雄性肉仔鸡270只,随机分到5个日粮处理组,进行为期42d的饲养试验。5种日粮是在基础日粮中加入0、50、100、150mg/kg的壳聚糖和50mg/kg的金霉素。结果表明:日粮中添加100mg/kg壳聚糖在提高日增重趋势的同时,提高了饲料转化效率,效果优于金霉素。在血清生化指标方面,100mg/kg壳聚糖组相比对照组降低了血清中TC、TG含量(P<0.05),提高了TPI、GF-1和GH含量(P<0.05),而对葡萄糖和尿酸含量无影响(P>0.05)。初步确定壳聚糖在肉鸡日粮中的适宜添加量为100mg/kg。壳聚糖的促生长作用可能与提高了血清中GH和IGF-1的分泌有关。     

Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.     

The intermittent feeding of anti-bacterial and-or antifungal agents to laying hens

A study was conducted in order to ascertain the effects of feeding large doses of various antibacterial (chlortetracycline, furazolidone, bacitracin) and/or anti‐fungal (nystatin, cupric sulphate) agents to laying hens on an intermittent basis. None of the drugs tested enhanced the performance of the birds when fed singly. However, birds that received a diet intermittently containing a broad‐spectrum antibiotic (110 mg/kg of diet) exhibited a performance superior to that of the control group when the antibacterial treatment was immediately followed by the feeding of a ration containing 55 mg nystatin/kg, during the 7 subsequent days.

It is possible that the intermittent, successive feeding of massive amounts of antibacterial and antifungal agents may act synergistically to promote egg production and efficiency of food utilisation. An economic evaluation of the data revealed that, at constant egg production levels, the feeding of chlortetracycline‐supplemented diet (110 mg/kg of diet) for 3 consecutive days, immediately followed by feeding a nystatin supplement (55 mg/kg of diet) for 7 consecutive days, the cycle being repeated every 4 weeks, led to a larger net profit than the feeding of chlortetracycline‐supplemented or unsupplemented diets.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Chlortetracycline supplementation of yearling dairy heifers

Chlortetracycline is an antibiotic that is used to increase weight gain, efficiency of gain, carcass grade, and conception rates. The objective of this experiment was to evaluate the effects of supplementation of 350 mg/d of chlortetracycline on ADG, G:F, BCS, thyroxine, and systemic glucose concentrations in yearling dairy heifers. Forty 12-mo-old Holstein heifers (initial BW = 363 +/- 21 kg) were housed in a free-stall barn with ad libitum access to feed and water for 104 d. A transition period was begun 14 d before the age of 12 mo to acclimate the heifers to the diet. The chlortetracycline-fed group (n = 20) consumed 328 +/- 8.2 mg of chlortetracycline/heifer daily. Measurements for BW, withers and hip heights, BCS, and health score were recorded weekly. Dry matter intake was measured daily. Blood was sampled every 4 d to determine plasma thyroxine and glucose concentrations and every 2 d to determine progesterone concentrations. Heifers were artificially inseminated on the first observed standing heat after 13 mo of age. There were no effects of chlortetracycline on ADG, G:F, withers and hip heights, BCS, blood glucose concentrations, peak progesterone concentrations, health, or conception rate. There was an interaction between treatment and time for chlortetracycline on serum thyroxine concentration. In the beginning of the experiment, serum thyroxine concentration was lower in heifers supplemented with chlortetracycline. There was no difference between treatments in thyroxine concentration at the end of the experiment. Chlortetracycline supplementation was not beneficial for yearling dairy heifers.     

The availability of tetracyclines in calves

The bioavailability of oxytetracycline (OTC) and chlortetracycline (CTC) was studied in non-fasting calves. The availability of OTC was found to be 5% and of CTC 37% after oral administration of 10 mg/kg. The availability was reduced when the drugs were given in a milk replacer or in cow's milk. The area under curve (AUC) was reduced 68% when OTC was given in milk replacer, the reduction of CTC availability was 40%. In milk the reduction was 72% for OTC and 47% for CTC. Calcium and iron caused a dramatic reduction of the serum levels. OTC was stored mixed in milk powder at room temperature for 6 months without loss in availability. OTC did not chelate calcium ions in serum. The conclusion drawn from the results was that CTC is more suitable than OTC for oral therapy in calves.     

Hydrolysis of phytic acid by intrinsic plant or supplemented microbial phytase (Aspergillus niger) in the stomach and small intestine of minipigs fitted with re-entrant cannulas

Hydrolysis of phytate in the stomach and the small intestine as influenced by intrinsic plant (wheat) and supplemented microbial phytase (A. niger) were investigated with six minipigs (40-50 kg initial BW) fitted with re-entrant-cannulas in the duodenum, 30 cm posterior to the pylorus (animals 1, 4, 5, and 6) and ileocecal re-entrant cannulas, 5 cm prior the ileocecal junction (animals 1, 2, and 3), respectively. Dietary treatments were as follows: (1) diet 1, a corn-based diet (43 U Phytase/kg DM); (2) diet 2, diet 1 supplemented with microbial phytase (818 U/kg DM) and (3) diet 3, a wheat-based diet (1192 U/kg DM). At 0730 and 1930 per animal 350 g diet mixed with 1050 ml de-ionized water were fed. Digesta were collected continuously and completely during 12 h after feeding. Duodenal recovery of dry matter and total phosphorus were 100% in the period between two feedings, irrespective of dietary treatment. In animals fed the wheat-based diet, dry matter left the stomach faster (p < 0.05) during the first hour after feeding than in animals fed the corn-based diets (41.3 vs. 31.0 and 25.8% of intake, respectively). Supplemented microbial phytase did not affect ileal dry matter digestibility of the corn-based diet. In the first hour after feeding, phosphorus concentration of the duodenal digesta of animals fed corn-based diets with or without supplemented microbial phytase (5.86, 6.19 mg total P/g DM) exceeded the dietary level considerably (4.30 and 4.21 mg total P/g DM) indicating a higher solubility of corn than wheat phosphorus in the stomach. Apparent ileal P absorption was higher (p < 0.05) in the wheat-based diet (37.6%) and corn-based diet supplemented with microbial phytase (34.3%) than in the unsupplemented corn-based diet (17.6%).     

Effects of processing barley on its digestion by horses

Four horses were randomly fed a diet containing rolled, micronised or extruded barley; the barley intake was adjusted to supply 2 g starch/kg bodyweight per day. During a 10-day acclimatisation period the horses were also fed 1 kg grass hay/100 kg bodyweight per day. Samples of blood and breath were collected at the end of each period after the test meal of barley had been fed after a 12-hour overnight fast. The glycaemic and insulinaemic responses of the horses were measured as an indication of the pre-caecal digestibility of starch, and postprandial breath hydrogen and methane were measured to detect microbial fermentation of starch. The highest peak serum glucose and serum insulin concentrations were observed after feeding the extruded barley, lower concentrations were observed after feeding the micronised barley and the lowest concentrations were observed after feeding the rolled barley. Breath hydrogen increased within four hours of feeding all the barley diets, and the mean (sd) peak hydrogen concentrations were 98.3 (55.2) ppm for rolled barley, 59.3 (31.5) ppm for micronised barley and 96.1 (51.9) ppm for extruded barley. There were wide variations within individual horses but these concentrations were not significantly different. Breath methane concentrations were very variable and, although there were no significant differences, there was a trend for higher methane concentrations after the feeding of rolled barley.     

Chlortetracycline in swine-bioavailability and pharmacokinetics in fasted and fed pigs

Chlortetracycline hydrochloride was administered intra-arterially (11 mg/kg) and as an oral drench (33 mg/kg) to ten 21.0-31.5-kg pigs. Five of the pigs were fasted 18 h prior to dosing and five of the pigs were fed ad libitum prior to dosing. The mean volume of distribution determined by area-under-the-curve calculations for the fasted pigs (0.967 +/- 0.210 l/kg) was significantly less (P less than 0.05) than the mean volume of distribution for the fed pigs (1.39 +/- 0.31 l/kg). Mean total body clearance of the drug was also significantly less (P less than 0.05) in the fasted pigs (0.165 +/- 0.055 l/kg/h) as compared to the fed pigs (0.307 +/- 0.053 l/kg/h). The elimination constants (beta) were not found to be statistically different (P less than 0.05): 0.1811 +/- 0.0057 for the fasted pigs; 0.2260 +/- 0.0461 for the fed pigs. The bioavailability for both groups was similar; 19.12 +/- 8.3% for the fasted pigs and 17.88 +/- 5.3% for the fed pigs. In a second experiment three groups of six pigs which weighed 34.5-44.1 kg were fed a corn-soy diet ad libitum. The rations were fortified with chlortetracycline at 100, 400 or 1000 mg chlortetracycline hydrochloride/kg feed. Chlortetracycline concentrations were determined in plasma samples collected over a 6-day period. Plasma chlortetracycline concentrations reach a plateau within 24 h after initial access to the trial diets and were highly correlated with the dose of the drug consumed (r2 = 0.97).     

Effect of feeding chlortetracycline or virginiamycin on shedding of salmonellae from experimentally-infected swine

Swine from a herd routinely fed subtherapeutic levels of chlortetracycline (CTC) were fed a diet containing 55 mg of CTC/kg, a diet containing 55 mg of virginiamycin/kg, or a control diet. All animals were inoculated with Salmonella typhimurium that was susceptible to tetracycline. The quantity, duration and prevalence of shedding of S. typhimurium were determined. The infecting organism was first recovered from the animals fed CTC or the control diet on d 2, from animals fed virginiamycin on d 7 and from animals in a second control group on d 10. The infecting organism was recovered in fewer samples obtained during the initial 7 d postinfection than in those obtained during the last 24 d of the study. Little transfer of resistance to the infecting organism seemed to have occurred from the resident microflora because only two isolates (1%) had resistant patterns that differed from that of the infecting organism. Feeding CTC or virginiamycin to swine did not significantly increase or prolong shedding of an experimentally infected tetracycline-susceptible strain of S. typhimurium. Neither antibiotic affected the drug resistance of the infecting organism.     

Effect of Low Dietary Magnesium on Immune Response and Osmoregulation of Atlantic Salmon

Abstract

The influences of dietary magnesium on immune response and on osmoregulation in parr of Atlantic salmon Salmo salar were determined. Groups of fish were fed a casein–gelatin diet unsupplemented (containing about 200 mg Mg/kg) or supplemented with either 300 or 500 mg Mg/kg dry diet (as MgSO₄) for 12 weeks before vaccination to produce fish with different Mg levels, and the feeding regime was continued throughout the study. No differences were observed between the treatment groups in serum-specific antibody levels every second week for 8 weeks after vaccination against Vibrio anguillarum serotypes O1 and O2. Both lysozyme levels and spontaneous hemolytic activities in serum were elevated in vaccinated fish compared with unvaccinated fish. Neither lysozyme activity, complement hemolytic activity, total protein in serum nor blood hemoglobin were affected by dietary Mg. The spontaneous hemolytic activity in serum was lower in fish fed the unsupplemented diet and highest in fish fed the diet supplemented with 500 mg Mg/kg. After 28 weeks on the diets supplemented with graded levels of Mg, a salinity tolerance test (32.5 g/L, 24 h) was performed. High mortality and elevated serum chloride concentrations in all groups after 24 h reflected a general salinity intolerance, but the highest serum chloride level was observed in fish fed the unsupplemented diet. This indicates that low dietary Mg affects the osmoregulation of Atlantic salmon.     

Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal

Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.     

Serum erythromycin concentration in sheep fed two diets

Serum erythromycin concentrations following a single IV injection (12.5 mg/kg) were compared in 6 sheep during feeding of a grass hay diet and a concentrate diet. The concentrate diet resulted in a mean decrease of at least 1 pH unit in forestomach fluid, but did not significantly alter either the serum drug concentrations or half-life. Variable antibacterial activity was present in forestomach fluid as early as 1 or 2 hours after injection. This study indicates that ion-trapping in forestomach fluid as a result of normal dietary changes does not require therapeutic dosage adjustment.     

Aspirin dosages for the dog.

Aspirin dosages calculated from published pharmacokinetic data were tested in 3 male and 3 female Basset Hounds. Emesis occurred frequently after dosing at the rate of 50 mg/kg of body weight, a dosage that would be required for a convenient 12-hour dosing interval. A dosage of 25 mg/kg every 12 hours avoided emesis but did not maintain serum salicylate concentrations within the desired range of 10 to 30 mg/100 ml. A dosage of 25 mg/kg every 8 hours resulted in serum salicylate concentrations varying from 12.5 to 17.8 mg/100 ml. It was concluded that a maintenance dosage of 25 to 35 mg/kg every 8 hours in optimal for the dog, based on extrapolation of data obtained in man.