Sulfamethazine residues in uncooked edible tissues of port following recommended oral administration and withdrawal.

Commercial feed rations containing sulfamethazine at the level of 110 ppm were fed for a period of 65 days to market pigs in a study simulating normal farm practices. The levels of sulfamethazine at the end of medication were in excess of 10 ppm in liver and kidney and up to 2.6 ppm in muscle tissues. Concentrations of sulfamethazine in tissues from pigs after withdrawal of medicated feed depleted to 0.1 ppm within nine days. The rate of depletion was similar for all tissues. It was observed that storage of tissue samples at freezer temperature (-20 degrees C) for 30 days further reduces sulfamethazine levels by 3 to 20% of their original value.     

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.     

Effect of pantothenic acid on disposition kinetics and tissue residues of sulphadimidine in chickens

Sulphadimidine was administered to chickens via the intracrop route to determine plasma concentrations of the unchanged sulphonamide and its acetylated derivatives, kinetic disposition, tissue residues and acetylation. The sulphadimidine was given alone (group 1) at a dose of 200 mg kg-1 bodyweight. Pantothenic acid was given via the intracrop route at a dose of 100 mg kg-1 bodyweight one hour before (group 2) and six hours after (group 3) sulphadimidine administration (200 mg kg-1 bodyweight intracrop). The highest plasma concentrations of sulphadimidine in groups 1, 2 and 3 were reached in 1.73, 1.62 and 1.71 hours, respectively, following intracrop administration. In birds of groups 1, 2 and 3 no sulphadimidine was detected at 72, 24 and 48 hours, respectively, following its administration. Estimation of sulphadimidine in most of the body tissues revealed that all tissues examined had lower concentrations than plasma. In chickens given pantothenic acid (groups 2 and 3) before and after sulphadimidine administration, an increase in the concentration of N4 acetylated derivatives of sulphadimidine was observed compared with birds given sulphadimidine alone (group 1).     

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.     

Pharmacokinetics and tissue residues of moroxydine hydrochloride in gibel carp,Carassius gibelio after oral administration

The pharmacokinetics and tissue residues of moroxydine hydrochloride were studied in gibel carp at water temperature of 15 and 25 °C. Samples (blood, skin, muscle, liver, and kidney) were collected over 10 days after the treatment and analyzed by high‐performance liquid chromatography with an ultraviolet detector. The results indicated that the influence of water temperature on the metabolism of the drug was significant. The plasma concentration–time data of moroxydine hydrochloride conformed to single‐compartment open model at the two water temperatures. There were higher absorption rate (t_1/2ka) and longer elimination half‐lives (t_1/2ke) at 15 °C (4.29 and 15.87 h, respectively) compared with those at 25 °C (3.02 and 4.22 h, respectively). The maximum plasma concentration (C_max) and the time‐point of maximum plasma concentration (T_p) were 2.98 μg/mL and 10.35 h at 15 °C and 3.12 μg/mL and 4.03 h at 25 °C, respectively. The distribution volume (V_d/F) of moroxydine hydrochloride was estimated to be 4.55 L/kg at 15 °C and 2.89 L/kg at 25 °C. The total body clearance (CL_b) of moroxydine hydrochloride was determined to be 0.25 and 0.49 L/(h·kg) at 15 °C and 25 °C, respectively; the areas under the concentration–time curve were 75.89 μg·h/mL at 15 °C and 42.33 μg·h/mL at 25 °C. The depletion of moroxydine hydrochloride in gibel carp was slower with a longer half‐life period, especially at lower water temperature that was tested.     

Pharmacokinetics and tissue residues of enrofloxacin in the largemouth bass (Micropterus salmoides) after oral administration

The study was carried out to evaluate the pharmacokinetic disposition of enrofloxacin (ENF) with a single dose of 20 mg/kg after oral administration in largemouth bass (Micropterus salmoides) at 28°C. The concentrations of ENF and of its metabolite ciprofloxacin (CIP) in plasma, liver, and muscle plus skin in natural proportions were determined using HPLC. The concentration–time data for ENF in plasma were best described by a two-compartment open model. After oral administration, the maximum ENF concentration (C_max) of 10.99 μg/ml was obtained at 0.60 hr. The absorption half-life (T_1/2Ka) of ENF was calculated to be 0.07 hr whereas the elimination half-life (T_1/2β) of the drug was 90.79 hr. The estimates of area under the plasma concentration–time curve (AUC) and apparent volume of distribution (Vd/F) were 1,185.73 μg hr/ml and 2.21 L/kg, respectively. ENF residues were slowly depleted from the liver and muscle plus skin of largemouth bass with the T_1/2β of 124.73 and 115.14 hr, respectively. Very low levels of ciprofloxacin were detected in the plasma and tissues. A withdrawal time of 24 days was necessary to ensure that the residues of ENF + CIP in muscle plus skin were less than the maximal residue limit (MRL) of 100 μg/kg established by the European Union.     

Critical review on the withdrawal period calculation for injection site residues

This review concerns a statistical method for calculating withdrawal period for injection site residues. A recently adopted Committee for Medicinal Products for Veterinary Use/European Agency for the Evaluation of Medicinal Product (CVMP/EMEA) guideline recommends to apply the same method for the calculation of withdrawal period for injection site residues as for other edible tissues. For reasons in this study developed below, this approach is deemed to be inappropriate for the injection site residues. The injection site residues often violate regression assumptions with regard to homoscedasticity (same variance in residue concentrations for different slaughter times) and linearity (of the mean depletion curve in log(e)-scale). The currently recommended method cannot adequately handle these aspects. An alternative pragmatic method taking into account the last slaughter time with all data below the reference threshold, combined with a safety span, is proposed for injection site residues. A nonparametric approach for calculating the withdrawal period is also presumed to be a sound alternative. The references commonly used are the Maximum Residue Limit (MRL) and the Acceptable Daily Intake (ADI). Unfortunately these references are not relevant to the acute risk exposure associated with injection site consumption. The use of alternative references, such as the Acceptable Single Dose Intake (ASDI) or the Acute Reference Dose (ARD) are thought to be more appropriate.     

Drug withdrawal times for performance horses and horses intended for food

To protect the health and welfare of horses, veterinarians must legitimately use therapeutic medications. Many drugs are appropriately used to treat various disease conditions of horses, yet many of them have the ability to affect athletic performance or leave residues in tissues. For performance horses, the primary reason to have drug rules is to ensure fair competition and to protect the welfare of the horses and riders. When medications are administered to horses intended for human consumption, it is the responsibility of the veterinarian to ensure that violative drug residues do not occur. If horses are to receive proper veterinary care, suitable information on drug detection times must be available to equine practitioners.     

Local tissue reaction to the administration of an inactivated Brucella ovis saline-in-oil vaccine by the intraperitoneal route

An inactivated Brucella ovis saline-in-oil vaccine was administered to 14 adult ewes using both the intraperitoneal route and the subcutaneous route. Pairs of animals were necropsied at intervals between 24 hours and ten weeks after injection. The nature of the local inflammatory reaction to the administration of the vaccine was similar at all sites. The lesion consisted of granulomatous inflammation arranged around droplets of oily vaccine. Diffuse peritonitis was seen at necropsy in 12 of the 14 animals. A local extraperitoneal inflammatory response at the injection site was present in four animals despite careful attempts to deposit the vaccine within the abdominal cavity. A second study of 30 rams vaccinated by the intraperitoneal technique confirmed that extraperitoneal deposition of vaccine commonly occurred and that approximately 20% of animals vaccinated by the intraperitoneal method still had peritonitis six months later.     

Local tissue reaction to the administration of an inactivated Brucella ovis saline-in-oil vaccine by the intraperitoneal route

Abstract

An inactivated Brucella ovis saline-in-oil vaccine? was administered to 14 adult ewes using both the intraperitoneal route and the subcutaneous route. Pairs of animals were necropsied at intervals between 24 hours and ten weeks after injection. The nature of the local inflammatory reaction to the administration of the vaccine was similar at all sites. The lesion consisted of granulomatous inflammation arranged around droplets of oily vaccine. Diffuse peritonitis was seen at necropsy in 12 of the 14 animals. A local extraperitoneal infammatory response at the injection site was present in four animals despite careful attempts to deposit the vaccine within the abdominal cavity. A second study of 30 rams vaccinated by the intraperitoneal technique confirmed that extraperitoneal deposition of vaccine commonly occurred and that approximately 20% of animals vaccinated by the intraperitoneal method still had peritonitis six months later.     

Effect of the route of administration on the mucosal and systemic immune responses to Lawsonia intracellularis vaccine in pigs

In an on‐farm study, 40 weaned piglets aged 3 weeks were vaccinated with Lawsonia intracellularis vaccine orally, IM or IP while a fourth group remained unvaccinated. All vaccinated animals showed increased serum levels of L. intracellularis‐specific IgG antibodies, but significantly elevated concentrations of specific IgG, IgA and cytokines were generated in ileal mucosal secretions from the orally and IP vaccinated pigs when examined at 17 days after vaccination.     

Total radioactive residues and clenbuterol residues in swine after dietary administration of [14C]clenbuterol for seven days and preslaughter withdrawal periods of zero, three, or seven days

Nine barrows (23.8 +/- 0.9 kg) and 9 gilts (23.1 +/- 0.9 kg) were used to determine the disposition of radiocarbon after oral [14C]clenbuterol (4-amino-alpha-[t-butylaminomethyl]-3,5-dichlorobenzyl [7-(14)C]alcohol hydrochloride) administration and to determine total and parent residues in edible tissues. Three barrows and three gilts, housed in metabolism crates, were fed 1 ppm [14C]clenbuterol HCl for seven consecutive days in three separate trials; a single barrow and gilt from each trial was slaughtered after 0-, 3-, or 7-d preslaughter withdrawal periods. Urine and feces were collected during the dosing and the withdrawal period; edible and inedible tissues were collected at slaughter. Total recovery of radiocarbon was 94.2 +/- 6.5%. Total clenbuterol absorption was greater than 75% for barrows and 60% for gilts. Total radioactive residues in tissues were not different (P > 0.05) between barrows and gilts. Concentrations of parent clenbuterol in liver, kidney, skeletal muscle, adipose tissue, and lung did not differ between barrows and gilts (P > 0.05). Total radioactive and parent residues declined in tissues as withdrawal period increased. After the 0-d withdrawal period, total liver residues (286 ppb) were approximately equal to lung residues, twice those of the kidney, and about 15 times those of adipose tissue and skeletal muscle. After a 7-d withdrawal period, total radioactive residues in liver (15 ppb) were roughly three times greater than lung, kidney, and adipose tissue total residues and about 13 times those of skeletal muscle total residues. Parent clenbuterol represented 79, 63, 42, 67, and 100% of the total radioactive residue in adipose tissue, kidney, liver, lung, and skeletal muscle, respectively, in hogs slaughtered with a 0-d withdrawal period. With increasing withdrawal period, the percentage of total radioactive residue present as parent clenbuterol within edible tissues (including lung) decreased, so that after a 7-d withdrawal period, 7, 16, and 29% of the total residue was composed of parent clenbuterol in kidney, liver, and lung, respectively. After a 7-d withdrawal period, parent clenbuterol exceeded the European maximum residue limit (0.5 ppb) 4.6-fold in liver and 2.4-fold in lung. In muscle, clenbuterol was approximately 40 times the limit after a 0-d withdrawal period but had dropped below 0.5 ppb after a 3-d withdrawal period. Results from this study indicate that clenbuterol HCl is well absorbed in swine and that the use of clenbuterol in this species in an off-label manner is inconsistent with human food safety standards used in developed countries.     

Comment on anthelmintic use in goats and the effect of route of administration

Abstract

Extract

In a recent publication in this journal(1) Bailey, KM. 1994. Anthelmintic use in goats and the effect of route of administration. New Zealand Veterinary Journal, 42: 37–8. [Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], administration of oral and injectable moxidectin (Vetdectin, Cyanamid N.Z. Ltd) to goats was found to result in faecal egg count reductions of 0% and 84% respectively, in infections that were predominantly composed of Ostertugia spp. The author considered that these results raised issues pertaining to the relative effectiveness of different routes of anthelmintic administration in goats and further suggested, as the animals were suffering from “water belly” at the time of treatment, that the occurrence of this syndrome may also have affected the pharmacodynamics of the anthelmintic.     

Influence of administration route on the biotransformation of amoxicillin in the pig

A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration ( P  > 0.05). After p.o. administration, the half-life of elimination ( t _1/2(el)) for AMA is at least two or three times the t _1/2(el) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open β-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.     

Anthelmintic use in goats and the effect of route of administration

The control of gastrointestinal parasites in goats by the use of anthelmintics has been and continues to be problematic. Products used successfully in sheep sometimes appear to be less effective than expected when used in goats. Parasites resistant to ivermectin have been reported in goats in New Zealand but not in sheep. I write to report a case that raises issues pertaining to the relative effectiveness of different routes of anthelmintic administration in goats.     

Pharmacokinetics and tissue residues of josamycin in fowls.

Josamycin is a macrolide antibiotic which is produced by fermentation of cultures of Streptomyces narbonensis. It was once administrated (18 mg/kg b. wt.) in fowls via intravenous, oral and intramuscular routes for determination of blood concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time-curve indicated a two compartments open model with an elimination half life value (t1/2 beta) of 1.83 +/- 0.06 hours. Both oral and intramuscular routes showed higher values, i.e. 2.33 +/- 0.13 and 2.85 +/- 0.17 hours. The lower apparent volume of distribution of Josamycin in fowls than one liter/kg elucidate higher distribution in blood than in tissues. Systemic bioavailability after both oral and intramuscular administration, i.e. 33.88 +/- 2.4 and 27.28 +/- 1.46% respectively, showed lower absorption from site of i.m. application. Josamycin was administered (18 mg/kg b. wt.) intramuscularly and orally once daily for 5 consecutive days. The drug peaked in serum 1 hour (intramuscular) and 2 hours (orally) after each dose. The recorded results revealed that serum level of Josamycin was higher after oral application (29.98 +/- 1.92 micrograms/ml) than after i.m. application. The drug persisted in the lung tissues and fat for 72 hours after administration and disappeared from all body tissues 96 hours after the last dose of repeated administration.