Commercial trials using emamectin benzoate to control sea lice Lepeophtheirus salmonis infestations in Atlantic salmon Salmo salar.

Two trials were conducted at commercial salmon farms to evaluate the efficacy of emamectin benzoate (Slice, 0.2% aquaculture pre-mix, Schering-Plough Animal Health) as a treatment for sea lice Lepeophtheirus salmonis (Krøyer) and Caligus elongatus Nordmann infestations in Atlantic salmon Salmo salar L. Trials were carried out in 15 m2 commercial sea pens, at temperatures of 5.5 to 7.5 degrees C and 10.8 to 13.8 degrees C. Each pen was stocked with 14,000 to 17,500 fish with mean weights of 0.44 to 0.74 and 1.33 to 1.83 kg. Fish were naturally infested with sea lice at the start of each trial. At Day -1, samples of 10 or 15 fish were taken from each pen to determine pre-treatment numbers of lice. Emamectin benzoate was administered in feed, to 4 replicate pens, at a dose of 50 micrograms kg-1 biomass d-1 for 7 consecutive days (Days 0 to 6). Sea lice were counted again, between Days 7 and 77, and comparisons made with untreated control fish. Despite adverse weather conditions, wide variations in fish weights and exposure to new infestations, treatment was effective against chalimus and motile stages of L. salmonis. In the autumn trial, efficacy at Day 27 was 89%, and lice numbers remained lower on treated fish than on control fish 64 d from the start of treatment. In the winter trial, reductions in lice numbers at low temperatures were slower but good efficacy was achieved by Day 35. Although control fish had to be treated with hydrogen peroxide at Day 21, fish treated only with emamectin benzoate on Days 0 to 6 still had 89% fewer lice than control fish at Day 35. There were very few C. elongatus present, but at the end of both trials numbers were lower on treated fish. No adverse effects were associated with treatment of fish with emamectin benzoate.

Pharmacokinetics and tolerance of florfenicol in Equidae.

Florfenicol was administered to horses and ponies at a dose rate of 22 mg/kg bwt by i.v., i.m. and oral routes. Following i.v. administration it had an elimination half-life of 1.8 ± 0.9 h, a body clearance of 0.4 ± 0.11/h.kg and a volume of distribution at steady-state of 0.7 ± 0.2 1/kg. It was highly bioavailable following i.m. (81%) and oral (83%) administration. Less than 15% of the administered dose was excreted unchanged in the urine during the 30 h following administration. Animals treated with florfenicol had elevated bilirubin concentrations. Florfenicol was well tolerated by animals in the present study although all animals had loose faeces following administration by each route. At present, florfenicol cannot be recommended for clinical use until multiple dose studies have been carried out to confirm its safety.

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration.

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min.kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations (Cmax) were 6.9 micrograms/mL at 360 min after intramammary administration and 2.3 micrograms/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The Cmax in milk was 5.4 micrograms/mL at 180 min after intravenous and 1.6 micrograms/mL at 600 min after intramuscular administration.

Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle.

The disposition of florfenicol after single intravenous and intramuscular doses of 20 mg of florfenicol/kg of body weight (b.w.) to feeder calves was investigated. Serum florfenicol concentrations were determined by a sensitive high performance liquid chromatographic method with a limit of quantitation of 0.025 microgram/ml. The extent of serum protein binding of florfenicol was only 13.2% at a serum florfenicol concentration of 3.0 micrograms/ml. Serum concentration-time data after intravenous administration were best described by a triexponential equation. Total body clearance and steady state volume of distribution were 3.75 ml/min/kg b.w. and 761 ml/kg b.w., respectively. The terminal half-life after intravenous administration was 159 min. The absolute systemic availability after intramuscular administration was 78.5% (range: 59.3-106%) and the harmonic mean of the terminal half-life was 1098 minutes, indicating slow release of the florfenicol from the formulation at the intramuscular injection site.

Tissue concentrations and pharmacokinetics of florfenicol in male veal calves given repeated doses.

The pharmacokinetic disposition of florfenicol was studied in male veal calves given 11 mg of florfenicol/kg of body weight, IV and 11 mg of florfenicol/kg PO every 12 hours for 7 doses. After florfenicol administration IV, the median elimination half-life was 222.8 minutes, whereas the median half-life of the distribution phase was 7.94 minutes. Median body clearance and apparent volume of distribution were 2.87 ml/kg/min and 0.907 L/kg, respectively. After florfenicol administration, PO, there was a wide variation in the calculated half-life, which was attributed to variation in the rate of florfenicol absorption. The half-life was 167.4 to 534.9 minutes after the first oral dose and 190 to 808.8 minutes after the seventh dose. The median bioavailability after the first oral dose was 0.8888. Peak and trough concentrations of florfenicol were increased after subsequent doses were administered, compared with those after the first oral dose. The percentage of protein binding in serum from one adult cow was 22% to 26%. Florfenicol concentrations in tissues and body fluids of male veal calves were studied after the seventh dose of 11 mg of florfenicol/kg. High concentrations of florfenicol were measured in the urine, kidney, and bile. Low concentrations were measured in the brain, CSF, and aqueous humor. Concentrations in all other tissues and fluids studied were similar to the concurrent serum concentration.

Single- and repeat-dose pharmacokinetic studies of chloramphenicol in horses: values and limitations of pharmacokinetic studies in predicting dosage regimens.

A single-dose pharmacokinetic study of chloramphenicol in propylene glycol was done in 6 horses after 22 mg/kg was administered IV. Serum drug concentrations obtained at various predetermined intervals were determined by an electroncapture gas-chromatographic technique. The time-concentration data were described by a 2-compartment open model, and various pharmacokinetic variables were estimated. The median elimination rate constant was estimated to be -0.0185 minute-1 (-0.0225 to -0.0148 minute-1), and the median half-life was 37.36 minutes (30.74 to 46.90 minutes). The median apparent volume of distribution and total body clearance were 1.46 L/kg (1.13 to 1.60 L/kg) and 25.56 ml/kg/min (23.66 to 32.21 ml/kg/min), respectively. On the basis of these data, single- and repeat-dose kinetic studies were done in another group of 6 animals. The drug was administered at a dosage of 22 mg/kg every 4 hours for 3 days. Blood samples were obtained for pharmacokinetic studies after the first and the last doses were given. The half-life, volume of distribution, and total body clearance did not change significantly (Wilcoxon signed rank test) after 3 days of therapy with chloramphenicol. The IV dose schedule for treating bacterial infections with organisms of different sensitivities has been determined from the estimates of the pharmacokinetic variables. The limitations of calculating the dose schedules for chloramphenicol on the basis of pharmacokinetic variables in horses are discussed.

Pharmacokinetics of florfenicol in veal calves.

The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22-mg/kg dose intravenously, orally after a 12-h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half-life was 171.9 min while the half-life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 l/kg, respectively. Following oral administration the median bio-availability (f) was 0.88 for calves dosed after a 12-h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.

Standardization of an experimental disease model of Streptococcus zooepidemicus in the equine.

A reproducible experimental disease model in horses using Streptococcus zooepidemicus was developed. An intravenous challenge dose of 1 X 10(10) colony-forming units (CFU), followed 24 h later with another challenge of 1 X 10(8) CFU of Strep. zooepidemicus produced the desired disease model. The disease was characterized by depression, pyrexia, anorexia, abnormal lung sounds, inflammation of joints, moderate to severe lameness, gradual loss of condition and emaciation. The effects of the disease on hematology, serum chemical profile and different protein fractions were studied. The disease state had no effect on serum glucose, sodium, potassium, chloride, urea nitrogen, creatinine, uric acid, calcium, phosphorus and enzymes SGOT or SGPT. However, the alkaline phosphatase showed a gradual decline. The serum iron levels dropped markedly and remained low to the last day of observations (post-infection day, PID 13). On serum protein electrophoresis, the albumin showed a gradual decrease; whereas, alpha II, beta and gamma globulin levels rose suggesting an immune response. The elevation of rectal temperatures and white blood cell counts related well with clinical observations. The serum iron levels proved very helpful in predicting the severity of clinical signs and often dropped before the onset of clinical signs and pyrexia.

A health index to evaluate clinically a beta-hemolytic streptococcal infectious disease model in the horse.

Quantification of the clinical manifestations of a disease has been a serious problem particularly as related to clinical trials or drug efficacy studies. Historically, this quantification has been limited to categorizing each patient into one of three or four groups, e.g. worse, no improvement, improved. This problem becomes serious when an investigation utilizes an experimentally induced animal disease model. A health index, which quantifies the clinical state of horses which have an experimentally induced beta-hemolytic streptococcal infection, is described. Aspects of experimental design and statistical analysis are also discussed in relationship to the use of the index for drug efficacy studies.

Clearance of penicillin G in the newborn calf.

Sodium penicillin G was administered intravenously (4545 IU/kg) to calves on the day of birth (12-24 h old) and at 5, 10, and 15 days of age. Serum was collected at varying intervals for 120 min after injection and analysed for penicillin G. The mean total body clearance (ClB) of penicillin G on the day of birth was 2.98 ml/min/kg compared to 4.83 ml/min/kg at 5 days, 3.11 ml/min/kg at 10 days and 4.65 ml/min/kg at 15 days of age. Clearances at 5 and 15 days were significantly (P less than or equal to 0.05) higher than on the day of birth. The half-life (t1/2 beta), however, did not change significantly over the 15-day period of the study. These results indicate that the newborn calf has an appreciable ability to excrete penicillin G before it is 24 h old, and that total body clearance of the antibiotic increases rapidly in the immediate postnatal period.

Pharmacokinetics and plasma protein binding (in vitro) of oxytetracycline in buffalo (Bubalus bubalis).

The pharmacokinetics of oxytetracycline given in a single dose (22 mg/kg) either IV or IM was studied in 4 female buffalo calves. The half-life (t1/2) after IV administration varied between 169.02 and 216.56 minutes and that after IM administration, between 630 and 990 minutes. The drug was distributed well in the body after IM administration (Vdarea 1.18 to 2.15 L/kg). The total body clearances varied between 1.02 and 1.45 and between 1.17 and 1.49 ml/kg/min after the IV and the Im dosings, respectively. It has been proposed that oxytetracycline is excreted mainly by glomerular filtration in the buffalo species, but tubular reabsorption also may have a small part. About 42% of the drug was bound to plasma proteins at concentrations of 2 to 20 micrograms of oxytetracycline/ml. The drug dosage schedules to maintain serum levels of 0.5, 1, 2, and 5 micrograms/ml also are determined.

A study on renal function in the Indian buffalo (Bubalus bubalis).

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in buffalo species (Bubalus bubalis) were estimated using a single injection technique. The total body clearances of inulin and para-aminohippuric acid (PAH) served as estimates of GFR and ERPF, respectively. Inulin and PAH were administered to animals as a single i.v. bolus. The time-concentration curves were determined for each compound. Three mathematical models were applied to the data. The two compartment model gave the best fit to the data. The single compartment model gave slightly higher values, but could be used in clinical and certain research situations to estimate renal functions when it is not practical to take large number of samples.