Drug residues in food animals II. Plasma and tissue kinetics of oxytetracycline in young cross-bred swine

Tissue distribution and elimination kinetics of oxytetracycline in sixteen organs and body fluids were determined in young pigs following intravenous and oral administration. Seventeen non-fasted pigs, 8–10 weeks of age, weight range 16.4–34.5 kg were dosed intravenously at a dose rate of 11 mg/kg bodyweight. An additional seventeen weaning pigs, 12–14 weeks of age, weight range 27.2–36.3 kg were dosed orally at a dose rate of 48–65 mg/kg bodyweight. Oxytetracycline was rapidly distributed (half-life, 6.71 ± 1.13 min) in swine. The mean volume of distribution was 1.26 ± 0.18 l/kg and overall body clearance was 3.82 ± 0.59 ml/kg/min. The elimination half-life of oxytetracycline in pigs was 3.87 ± 0.62 h, which is shorter than has been observed in other domestic animal species. Oxytetracycline became rapidly and efficiently involved in enterohepatic cycling, with as much as 70% of a total intravenous dose being available for reabsorption from the gastrointestinal tract within 1 h after administration. This high degree of enterohepatic recycling prolonged the half-life, and the large amount of drug that entered the enteric tract contributed to the high volumes of distribution and high k ₁₂/ k ₂₁ ratios. The excellent tissue penetration of this drug further contributed to the high volume of distribution and high k ₁₂/ k ₂₁ ratios obtained. Relationships between plasma and tissue depletion for several major edible organs were found to be statistically significant. Blood plasma is proposed as a body fluid for monitoring oxytetracycline tissue residues.     

Drug residues in food animals. I. Plasma and tissue kinetics of chloramphenicol in young cross-bred swine

Eighteen non-fasted, 12–16 week old pigs weighing between 20 and 40 kg were dosed with chloramphenicol intravenously at a dose rate of 22 mg/kg body weight. The pharmacokinetics of chloramphenicol were determined in blood plasma and sixteen selected organs and body fluids. The elimination half-life in plasma was estimated to be 2.66pL1.06 h and volume of distribution was 1.39pL0.32 I/kg. The body clearance of chloramphenicol was estimated to be 6.64pL1.52 ml/kg/min. The elimination half-life in tissue was found to range from 1.25 h in kidney to 5.89 h in fat. Most major organs ranged from 2.0 to 5.0 h. Significant correlations were found to exist between plasma concentrations and most major organ concentrations. Chloramphenicol concentrations in muscle, spleen, lung, stomach content, and large intestine content were found to exist slightly beyond the time when concentrations were negative in plasma. However, urine levels exceeded tissue levels at the last slaughter interval. It appears that serum or urine would be a good body fluid for monitoring chloramphenicol residues in tissues, whereas stomach content might be used as an indicator for chloramphenicol treatment for many days after therapy with the drug.     

Drug residues in food animals

A total of 292 field investigative reports of drug residues in food animals for 1983 to 1988 were analyzed. The investigations had been conducted by the Food and Drug Administration (FDA) and the Virginia State Veterinarian's Office, in cooperation with the Center for Veterinary Medicine of the FDA, to trace residues reported by the USDA Food Safety and Inspection Service to the source of the animal and the administration of the drug. The analysis disclosed the following. (1) Antibiotic residues were most often associated with streptomycin, penicillin, oxytetracycline, and neomycin. Sulfamethazine was, by far, the most frequently cited sulfonamide. (2) Residues are being found predominantly in cows, veal calves, and market hogs (barrows and gilts). (3) The cause of drug residue most frequently cited by the field investigators was failure to observe the withholding time for the drug. Almost half of these investigations revealed that the individual responsible for the sale of the animal did not know the proper withholding time for the drug. Failure to maintain adequate records was also a contributing factor. (4) The producer was considered to be the responsible party in over 80% of the cases for which responsibility was determined. (5) Residues associated with injectable drugs were investigated most frequently. Long-acting and sustained-release products were most often associated with penicillin and oxytetracycline residues. (6) The 2 most common sources of purchase for the drugs involved in the investigations were the feed/farm supply store and the veterinarian. (7) Unapproved drug use was not a major cause of residues.     

Extralabel use of penicillin in food animals

Penicillin is one of the most commonly detected drug residues in tissues and milk, and is the antimicrobial for which information is most often sought through FARAD.     

Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses

OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography. RESULTS: Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.     

液相色谱法测定猪组织中阿维菌素类药物残留量

动物组织中残留的阿维菌素、依维菌素和多拉菌素经乙腈提取,碱性氧化铝固相萃取柱净化后,与荧光衍生化试剂反应,产物用高效液相色谱(荧光检测器)进行检测,实现了阿维菌素类药物的残留分析.本方法在猪组织中测定阿维菌素类药物的检测限为1μg/kg;在猪组织中添加浓度为1、2、5μg/kg时的回收率为55%～75%.     

Distribution of penicillin G in serum and tissue cage fluid in cattle

The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were lower than in serum and maximum was reached much later. Intravenous injection of benzyl-penicillin gave significantly higher levels in TCF than intramuscular injection. The penetration after procaine penicillin was very slow. The results showed that the serum peak rather than the area under curve determines the penetration of penicillin. Repeated intramuscular injections of benzylpenicillin and procaine penicillin caused an accumulation of penicillin in TCF. Similar levels were however reached by one single intravenous injection. The clinical counterparts to the used tissue cage model are abscesses. It was concluded that if high penicillin concentration are desireable in such foci, the drug must be given in a way that gives as high serum peaks as possible.     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

动物性食品中青霉素类抗生素残留检测方法--微生物法

农业部于2003年1月22日发布第236号公告,发布12个动物性食品中兽药残留检测方法。方法之九:动物性食品中青霉素类抗生素残留检测方法——微生物法。 动物性食品中青霉素类抗生素残留检测方法——微生物法 1 范围 本标准规定了动物性食品中青霉素类抗生素用标准曲线法进行定量,以青霉素酶法进行判定。 4.2 试剂和材料 以下所用试剂,除特别注明者     

The role of penicillin G potassium in managing Clostridium perfringens in broiler chickens

The efficacy of penicillin G potassium (Pot-Pen) administered via drinking water to manage necrotic enteritis (NE) was investigated in a Clostridium perfringens (CP) challenge study using 1600 broiler chickens assigned to one of four treatment groups: nonchallenged, nonmedicated; challenged, nonmedicated; challenged, Pot-Pen 0.2 g/L; challenged, Pot-Pen 0.4 g/L. Overall mortality due to NE was significantly reduced among Pot-Pen-treated pens; mortality due to other causes did not differ among the treatment groups. Among all birds, growth performance parameters were significantly improved among Pot-Pen-treated pens. When considering birds randomly sacrificed 4 days post-Pot-Pen initiation, mean NE lesion scores were greatest among the challenged, nonmedicated pens; only one of 80 randomly sacrificed birds treated with Pot-Pen had NE lesions. Among the nonmedicated control pens, body weight (BW) was significantly greater among birds that did not have NE-associated lesions. When sacrificed birds were stratified by NE lesion score, there were no significant differences in BW among the treatment groups. Results of this study suggest that CP-associated subclinical disease can significantly reduce broiler performance. Furthermore, the positive effects of treatment with Pot-Pen appeared to be associated with the prevention and/or treatment of NE-specific lesions.     

动物性食品中青霉素类抗生素残留检测方法--微生物法

农业部于 2 0 0 3年 1月 2 2日发布第 2 3 6号公告 ,发布 1 2个动物性食品中兽药残留检测方法。方法之十二 :动物性食品中青霉素类抗生素残留检测方法———微生物法。     

Evaluation of the effects of penicillin G potassium and potassium chloride on the motility of the large intestine in horses

OBJECTIVE: To evaluate effects of IV administration of penicillin G potassium (KPEN) or potassium chloride (KCl) on defecation and myoelectric activity of the cecum and pelvic flexure of horses. ANIMALS: 5 healthy horses. PROCEDURE: Horses with 12 bipolar electrodes on the cecum and pelvic flexure received KPEN or KCl solution by IV bolus 4 hours apart. Each horse received the following: 2 X 10(7) U of KPEN (high-dose KPEN) followed by 34 mEq of KCl (high-dose KCl), 1 X 10(7) U of KPEN (low-dose KPEN) followed by 17 mEq of KCl (low-dose KCl), high-dose KCl followed by high-dose KPEN, and low-dose KCl followed by low-dose KPEN. Number of defecations and myoelectric activity were recorded for 60 minutes. The first three 5-minute segments and first four 15-minute segments of myoelectric activity were analyzed. RESULTS: Number of defecations during the first 15-minute segment was greater after high-dose KPEN treatment than after high-dose or low-dose KCl treatment. Compared with reference indexes, myoelectric activity was greater in the pelvic flexure for the first 5-minute segment after high-dose KCl treatment, in the cecum and pelvic flexure for the first 5-minute segment and in the pelvic flexure for the first 15-minute segment after low-dose KPEN treatment, and in the pelvic flexure for the first and second 5-minute segments and the first three 15-minute segments after high-dose KPEN treatment. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of KPEN stimulates defecation and myoelectric activity of the cecum and pelvic flexure in horses. Effects of KPEN may be beneficial during episodes of ileus.     

Survey of chloramphenicol residues in diseased swine.

Tissue samples from 279 hogs suspected of having received antibiotic treatment were collected at federally-inspected abattoirs and submitted for chloramphenicol residue analysis during August and September 1984. Injection sites (when present), kidneys or muscle samples were tested by one of two gas chromatographic methods. Kidney samples were also tested at the abattoirs by the Swab Test On Premises. Thirty-one animals (11%) were found with detectable levels ranging from 1 part per billion to 5727 ppb. Highest levels were found at the injection sites, while levels in muscle tissue did not exceed 500 ppb. None of the kidneys from animals found to contain chloramphenicol residues produced a positive Swab Test On Premises result attributable to the presence of chloramphenicol. Twelve kidneys from animals free of chloramphenicol residues produced positive Swab Test On Premises results. Of these, five contained penicillin or streptomycin, but antibiotic residues were not detected in the remaining seven. In addition to the samples collected for this survey, samples from eight hogs representing a herd which had been treated for pneumonia were submitted by an abattoir in Manitoba in November 1984. Chloramphenicol levels in these animals ranged from 0.1 to 73 parts per million in the injection sites, and from 0.04 to 21 ppm in the muscle tissues. The survey data indicated that there were a significant number of animals reaching the abattoirs with detectable chloramphenicol residues, and that the Swab Test On Premises procedure was ineffective in detecting these animals.     

Antibiotic residues in milk following bulbar subconjunctival injection of procaine penicillin G in dairy cows

OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a concentration that is detectable following bulbar subconjunctival injection in lactating dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 66 Holstein cows that were at least 2 weeks past calving and had not been treated with antibiotics in the preceding 30 days. PROCEDURE: Cows were randomly assigned to receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar subconjunctival injection or remain untreated. Composite milk samples were collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after treatment. Milk samples were tested by use of a commercial test for beta-lactam antibiotics. RESULTS: Among penicillin-treated cows, the first positive test results were observed 4 hours after treatment, and the last positive result was observed 22 hours after treatment. The percentages of positive test results before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0, 9, 87, 42, 8, 0, and 0%, respectively. None of the untreated cows had positive test results for beta-lactam antibiotics at any sampling time. CONCLUSIONS AND CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a single subconjunctival injection of procaine penicillin G in cows. This result should be considered when recommending milk withholding periods following the administration of penicillin by this route in lactating dairy cows.     

Isometamidium in goats: disposition kinetics, mammary excretion and tissue residues

The pharmacokinetics of the antitrypanosomal drug isometamidium were studied in lactating goats after intravenous and intramuscular administration at a dose of 0.5 mg/kg body weight, in a crossover design at an interval of 6 weeks. Following intravenous administration, the half-life of the disappearance of the drug from plasma during the terminal phase was 3.2 h, and the mean residence time was 2.4 h. The apparent volume of distribution averaged 1.52 l/kg, and the mean total body clearance was 0.308 l/kg/h. After intramuscular administration, the absolute bioavailability was low, averaging 27%. This was consistent with a low mean maximum concentration of 24 ng/ml which occurred after 6 h. No drug was detectable (less than 10 ng/ml) in milk samples collected over a period of 14 days following drug administration by either the intravenous or intramuscular route. In tissues analysed when the goats were killed 6 weeks after administration of the second dose, no drug was detectable (less than 0.4 micrograms/g wet tissue) in the liver, kidney and muscle. However, at the injection site, drug concentrations varied from less than 0.4 to 18.8 micrograms/g wet tissue.     

Influence of the local tolerance on the pharmokinetics of two penicillin G preparations in cattle and swine

The addition of citrate buffer to a penicillin G preparation for injection was in a preliminary study found to improve the local tolerance in rabbits. In the present study 2 penicillin G preparations with different citrate buffer content was tested in the target species swine and cattle. The results of the local tolerance studies indicated that the preparation with the highest citrate content caused less tissue damage. In swine this preparation gave 100% higher maximum levels in serum than the more tissue irritating preparation. In calves the most irritating preparation showed significantly longer half-life. The results indicated that the local tolerance may influence the serum levels in a way that may influence the penetration of penicillin.