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.     

A comparison of some of the pharmacokinetic parameters of three commercial sulphadiazine/trimethoprim combined preparations given orally to pigs

Three sulphadiazine/trimethoprim preparations were administered orally during feeding to pigs. Six male and six female pigs were used. Clinically important pharmacokinetic parameters of the two drugs in the three preparations were determined and compared.The plasma concentrations of sulphadiazine and trimethoprim increased rapidly in the pigs followed by a quite rapid decrease from 4 to 12 h after oral administration. The mean values of the absorption half-lives of sulphadiazine and trimethoprim were 0.9–1.6 h and 0.5–0.8 h, respectively. The corresponding values for the elimination half-lives of sulphadiazine and trimethoprim were 3.1–4.3 h and 3.4–6.0 h, respectively. There were no significant differences between the pharmacokinetic parameters of the two compounds in the three preparations with the exception of T_max for sulphadiazine and t_1/2 for trimethoprim. Comparative bioavailability calculations showed no statistically significant differences between sulphadiazine and trimethoprim in the three preparations.The weight increase of the pigs during the experimental period (mean = 37.3–64.9 kg) did not cause differences in the kinetics of the two drugs which could have consequences for the use of the three combined preparations in clinical practice.No unacceptable or antibacterial residues of sulphadiazine or trimethoprim were found in the kidneys of pigs slaughtered at 5, 7 and 10 days after administration.     

Transdermal delivery and intramuscular injection of trimethoprim/sulphadiazine in sucking piglets

Summary

The pharmacokinetics of a combination of trimethoprim (TMP) and sulphadiazine (SDZ) after topical application to sucking piglets was compared with the pharmacokinetics after intramuscular injection. A long‐lasting and fairly constant SDZ/TMP concentration ratio in plasma was obtained after topical application. The mean plasma concentration of TMP ranged from 0.091 to 0.17 μg/ml and that of SDZ from 0.72 to 1.1 μg/ ml for at least 24 h. TMP and SDZ had different half‐lives after intramuscular injection. Transdermal delivery of a combined preparation of TMP/SDZ may be usable for colibacillosis of sucking piglets, although the bioavailability of the drugs is poor.     

Transdermal delivery and intramuscular injection of trimethoprim/sulphadiazine in sucking piglets.

The pharmacokinetics of a combination of trimethoprim (TMP) and sulphadiazine (SDZ) after topical application to sucking piglets was compared with the pharmacokinetics after intramuscular injection. A long-lasting and fairly constant SDZ/TMP concentration ratio in plasma was obtained after topical application. The mean plasma concentration of TMP ranged from 0.091 to 0.17 micrograms/ml and that of SDZ from 0.72 to 1.1 micrograms/ml for at least 24 h. TMP and SDZ had different half-lives after intramuscular injection. Transdermal delivery of a combined preparation of TMP/SDZ may be usable for colibacillosis of sucking piglets, although the bioavailability of the drugs is poor.     

A field trial to assess the therapeutic and prophylactic effect of a foot rot vaccine in sheep

An 18-week field trial was conducted on a sheep ranch to evaluate the therapeutic and prophylactic effect of a commercial foot rot vaccine. Two hundred sheep were included in the study, 100 with detectable foot rot lesions and 100 without. Approximately 50 sheep from each group were selected randomly and vaccinated twice against foot rot at a 6-week interval in the late spring 1984; the remaining sheep acted as nonvaccinated controls. Therapeutic effect of the vaccine was demonstrated by a cure rate of 53% in vaccinated, foot rot-affected sheep vs a cure rate of 19% in nonvaccinated, foot rot-affected sheep. Prophylactic effect of the vaccine was demonstrated by a foot rot prevalence at the end of the 18-week period of 9% for vaccinated sheep vs 53% for nonvaccinated sheep. Associations of foot rot lesions and vaccination with body condition were found to be significant, as was the association between foot rot lesions and mortality.     

The use of sulfonamides and sulfonamide/trimethoprim combinations as animal feed drugs for pigs in Schleswig-Holstein

An evaluation of production orders for medicated feedingstuffs for pigs given in 1998 in Schleswig-Holstein showed sulphonamides and combinations of sulphonamides and trimethoprim as frequently used antibiotical ingredients. The presented study analyses the production orders which include sulphonamides and combinations of sulphonamides and trimethoprim in more detail. There were large deviations to the rules of good clinical practise for the use of antibiotics. The applied dosage was often lower than suggested in the literature.     

Aspects on feed related prophylactic measures aiming to prevent post weaning diarrhoea in pigs

The ability of feed related measures to prevent or reduce post weaning diarrhoea (PWD) was examined in a split litter study including 30 pigs from 6 litters allotted into 5 groups. Four groups were exposed to 3 pathogenic strains of E. coli via the environment at weaning. Three of them were given zinc oxide, lactose+fibres or non-pathogenic strains of E. coil as probiotics. The challenged and the unchallenged control groups were given a standard creep feed. Diarrhoea was observed in all challenged groups but not among uninfected animals, and the incidence of diarrhoea was lower in the group given nonpathogenic E. coli compared to all other challenged groups. The severity of PWD also differed between litters. When corrected for mortality due to PWD, a decreased incidence of diarrhoea was also seen in the groups given zinc oxide or lactose+fibres. The dominating serotype of E. coil within faecal samples varied from day to day, also among diarrhoeic pigs, indicating that diarrhoea was not induced by one single serotype alone. The diversity of the faecal coliform populations decreased in all piglets during the first week post weaning, coinciding with an increased similarity between these populations among pigs in the challenged groups. This indicated an influence of the challenge strains, which ceased during the second week. The group given lactose+fibres was least affected with respect to these parameters. In conclusion feed related measures may alleviate symptoms of PWD.     

A mail survey of the efficacy of prophylactic medication in feed and/or water of feedlot calves.

A mail survey of feedlot owners was conducted to evaluate the efficacy of prophylactic antimicrobials, given in the water, or in the ration at preventing illness and/or death. One hundred and twenty-seven farmers from southwestern Ontario collaborated in the study. The percentage of calves requiring individual antimicrobial treatment, for any reason within 28 days of arrival was 22.6% (median 17.8%) and 0.6% (median 0.2%) died in that period. The use of medicated starter rations was not associated with either treatment or mortality rates until the effects of a number of other variables were controlled, analytically. Thereafter, the use of medicated feed was associated with a decrease in mortality rate, but was unrelated to morbidity rate. Overall, the use of medicated water was not associated with treatment or mortality rates. The use of sulphonamides was associated with decreased morbidity, but increased mortality rates. After controlling, analytically using multiple regression, the effects of other variables, the use of medicated water was associated with a significant increase in mortality rates. The other major factors which influenced mortality rates were the number of calves per group, the number of subgroups of calves in each group and whether the group contained cattle from different sources; all were related to increased mortality rates. During a two year period, more feedlot owners appeared to be using medicated rations as opposed to medicated water, as a means of providing antimicrobials to their newly arrived calves.     

黑麦草饲喂肉猪效果试验

黑麦草属禾本科优质牧草，具有适应性强、产量高、适口性好、易于家畜消化等特点。其鲜草中含粗蛋白质３．５８％～３． ８８％；干物质 １６． ２％；赖氨酸０． ６１％，是发展草－畜配套型畜牧业的选用牧草之—。为了研究其喂猪最佳的比例、饲喂效果和经济效益，给推广黑麦草喂猪提供科学依据，特进行本次试验。１试验材料与方法１．１时间与地点试验在我市城富某养猪专业户中进行，预饲期７ｄ，正饲期由１９９９年９月１２日至１９９９年１２月１２日，试验期９０ｄ。１．２试验猪的选择与分组选择窝别、性别、体重基本一致的杜、长、太…     

Prevention of pleuropneumonia in pigs by in-feed medication with sulphadimethoxine and sulphamethoxazole in combination with trimethoprim

The prophylactic effect of in-feed medication of conventional pigs with sulphadimethoxine (SDM), sulphamethoxazole (SMX), and trimethoprim (TMP) was tested by using an Actinobacillus pleuropneumoniae infection model. In each of five experiments, six pigs were given medicated feed twice daily and three pigs received antibiotic-free feed and served as positive (unmedicated, infected) controls. The following drugs or drug combinations were tested (in mg per kg feed): 500 SDM + 100 TMP, 500 SMX + 100 TMP, 125 SMX + 25 TMP, 125 SMX (alone) and 25 TMP (alone). After six days of feed medication, all animals were endobronchially inoculated with A. pleuropneumoniae in a dose of 1-3.10(4) colony-forming units (CFU). The response to the challenge in all control pigs was characterized by fever, lethargy, anorexia, reduced water consumption, and laboured breathing. At autopsy all controls manifested a fibrinous haemorrhagic pleuropneumonia. In-feed medication with 500 SDM + 100 TMP, 500 SMX + 100 TMP as well as 125 SMX + 25 TMP resulted in an effective protection against the challenge in all treated animals. After consumption of feed medicated with 125 mg per kg SMX or 25 mg per kg TMP, pleuropneumonia was evident in all challenged pigs. The results of this study indicate an in vivo potentiation of SMX and TMP in pigs against this respiratory tract pathogen.     

Comparative effects of oral administration of trimethoprim/sulphadiazine or oxytetracycline on the faecal flora of horses

A study was carried out on the bacteriological faecal flora of horses before and after oral doses of oxytetracycline or trimethoprim plus sulphadiazine. Administration of oxytetracycline was rapidly followed by large increases in counts of coliforms. Bacteroides and Streptococcus species, the disappearance of Veillonella species, the appearance of Clostridium perfringens type A in large numbers and the accumulation of watery fluid in the rectal contents. These changes were not seen following administration of trimethoprim-sulphadiazine and it was concluded that oral treatment of horses with this combination was unlikely to be accompanied by the hazard of inducing colitis.     

Effect of feeding on the fate of orally administered phenylbutazone, trimethoprim and sulphadiazine in the horse

Phenylbutazone, sulphadiazine and trimethoprim were administered to three horses on two occasions, recently fed and unfed, and the effect of feeding on the pharmacokinetics of the three drugs assessed. The mean peak concentrations of phenylbutazone and trimethoprim were reduced by feeding by 34 and 75 per cent, respectively. The pharmacokinetics of sulphadiazine were not significantly affected.     

Pharmacokinetics of a sulphamethoxazole/trimethoprim formulation in pigs after intravenous administration

Plasma disposition, metabolism, protein binding and renal clearance of sulphamethoxazole (SMZ) and trimethoprim (TMP) were studied in four pigs after intravenous administration at a dose of 40 and 8 mg/kg, respectively. SMZ and TMP were quickly eliminated (mean elimination half-lives: 2.7 and 2.4 h, respectively). SMZ was predominantly acetylated; no hydroxy and glucuronide derivates could be detected in plasma and urine. TMP was 0-demethylated into 4-hydroxytrimethoprim (M1) and 3-hydroxytrimethoprim (M4) metabolite and subsequently extensively glucuronidated. SMZ, TMP and its M1 metabolite were excreted predominantly by glomerular filtration, while N4-acetylsulphamethoxazole and glucuronide conjugates of the M1 and M4 metabolites of TMP were actively eliminated by tubular secretion. The proportional drug percentage being present in the urine as parent compound was 13.1% for TMP and 16.0% for SMZ. The glucuronide conjugates of the M1 and M4 metabolites formed the main part (81.5%) of urinary TMP excretion pattern.     

A field study on feed supplementation, body weight and selected blood parameters in local pigs in Laos

The aim of the present study was to investigate feed allowances, body weight (BW), haematocrit, haemoglobin, plasma ionised calcium (iCa), sodium, potassium, pH and glucose concentration and faecal K/Na ratio in local growing pigs, sows and piglets kept by small-holder farmers in Laos. Starting hypotheses were that (1) local pigs are under fed, (2) BW is higher in pigs receiving supplementary feed and (3) the blood profile of pigs subjected to very poor nutrition is outside the normal range. On 54 pig-keeping smallholdings in Borikhamxay province, Lao PDR, daily feed allowances were weighed and BW recorded for 27 lactating sows, 54 piglets and 27 growing pigs. Blood samples were collected from the vena jugularis in all pigs. Feed supplementation did not affect BW, but plasma iCa concentration was outside the normal range for all pigs. There was a tendency for lower faecal K/Na ratio in Na-supplemented sows. The results confirm that local pigs in small-scale production systems in Laos suffer from poor nutrition. The most important challenge for farmers appears to be provision of more feed, particularly feed with a high Ca content.     

自配料与商品料对生长猪育肥效果比较

选用 12头平均体重 36 6± 0 9kg(P >0 0 5 )、日龄相近、健康的大约×清平二元杂交生长猪 ,随机分为Ⅰ、Ⅱ、Ⅲ组处理 ,分别饲喂自配料 +自配添加剂、自配料、商品料进行试验 ,试验期为 4 0d。结果显示 :(1)Ⅰ、Ⅱ、Ⅲ组处理的料肉比分别为 3 5 3、3 5 7、3 80 ,Ⅰ组比Ⅲ组料肉比下降 7 1% ,Ⅱ组比Ⅲ组下降 6 1% ;饲料成本下降 18 8%。 3组间的平均日增重无显著差异 (P >0 0 5 )。 (2 )增重营养成本 ,DE :Ⅰ组比Ⅲ组下降 5 0 % ,Ⅱ组比Ⅲ组下降 4 0 % ;CP :Ⅰ组比Ⅲ组下降 5 0 % ,Ⅱ组比Ⅲ组下降 3 6 %。     

Fermented and nonfermented liquid feed to growing pigs: effect on aspects of gastrointestinal ecology and growth performance

The effect of feeding dry feed (DF), nonfermented liquid feed (NFLF), and fermented liquid feed (FLF) to growing pigs on aspects of gastrointestinal ecology and on performance was investigated. Nonfermented liquid feed was prepared by mixing feed and water at a ratio of 1:2.5 immediately before feeding. Fermented liquid feed was prepared by mixing feed and water in the same ratio as NFLF, and stored in a tank at 20 degrees C for 4 d, after which half the volume was removed twice daily at each feeding and replaced with the same volume of feed and water mixture. A total of 60 pigs (initial BW of 30.7 kg) from 20 litters was used. Twenty pigs, housed individually, were allotted to each of the diets and fed restrictively. Five pigs from each diet were sacrificed at an average BW of 112 kg and digesta from the gastrointestinal tract (GI-tract) was obtained to examine variables describing some aspects of the gastrointestinal ecology. Fermented liquid feed contained high levels of lactic acid bacteria (9.4 log cfu/g) and lactic acid (approximately 169 mmol/kg), low levels of enterobacteria (<3.2 log cfu/g), and had a low pH (4.4). Nonfermented liquid feed contained 7.2 log cfu/g of lactic acid bacteria, and 6.2 log cfu/g of enterobacteria, which indicated that fermentation had started in the feed. The pigs fed FLF had the lowest levels of enterobacteria along the GI-tract (<3.2 to 5.0 log cfu/g), and those fed NFLF the highest levels (5.7 to 6.6 log cfu/g; P < or = 0.02). Fermented liquid feed caused a decrease in gastric pH from 4.4 and 4.6 for DF and NLF, to 4.0 (P = 0.003), and increased numerically the gastric concentration of lactic acid (P = 0.17) from 50 to 60 mmol/kg in the DF and NFLF treatments to 113 mmol/kg in the FLF treatment. The animals fed NFLF showed the highest weight gain (995 g/d) and feed intake (2.14 kg/d), and those fed FLF the lowest values (weight gain, 931 g/d; feed intake, 1.96 kg/d; P = 0.003 for weight gain, and P < 0.001 for feed intake). The results from the present study indicate that feeding FLF as prepared here may be a valid feeding strategy to decrease the levels of enterobacteria in the GI-tract of growing pigs, whereas feeding liquid feed that has started to ferment (high levels of enterobacteria and high pH as with NFLF) increases the presence of these undesirable bacteria. Nonetheless, higher daily feed intake and body weight gain are obtained when feeding NFLF compared with feeding FLF or DF.     

饲料添加剂对奶牛产奶和繁殖性能影响的研究

近年来青岛地区的奶牛养殖发展迅速,部分奶牛养殖户自配精、粗饲料,但因其缺乏一定的科技知识,使得日粮的有效营养成分失衡,从而影响奶牛产奶和繁殖性能的发挥。为此,我们选择在奶牛混合精料中加入复合添加剂,观察其对奶牛产奶和繁殖性能的影响。