Pharmacokinetics of an injectable long‐acting parenteral formulation of doxycycline hyclate in pigs

Based on its ideal PK/PD ratios, doxycycline hyclate (DOX‐h), a time‐dependant antibacterial, is ideally expected to achieve sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer‐based matrix was used to produce a 10% long‐acting injectable preparation (DOX‐h‐LA) and its serum concentrations vs. time profile investigated after its injection to pigs in the pericaudal s.c. by parallel design. Results were compared with the forced oral bolus dose and i.v. pharmacokinetics of DOX‐h. For this study, 12 recently weaned pigs per group were included in this trial, and a dose of 20 mg/kg was injected in all cases. DOX‐h‐LA showed the greatest values for bioavailability (115.38%); maximum serum concentration (Cmax) value was 1.5 ± 0.2 with a time to reach Cmax of 3.41 ± 0.04 h and an elimination rate constant of 70.93 ± 0.87 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose interval of at least 5 days can be achieved for DOX‐h‐LA, whereas p.o. and i.v. dosing of DOX‐h may only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this trial, and no visible remnants of the preparation were detected neither fibrosis was observed after a thorough macroscopic and histopathological analysis.     

The effects of physostigmine on the electroretinogram in the beagle dog

The purpose of the study was to correlate electroretinogram (ERG) parameters with increasing levels of plasma, erythrocyte and ocular tissue cholinesterase inhibition using the beagle dog as a model for human neurovisual toxicity. The anticholinesterase compound physostigmine was administered at various steady-state intravenous infusion rates based on pharmacokinetic estimates of plasma and red blood cell cholinesterase inhibition. The most sensitive parameter was the b-wave amplitude of the rod response, which was significantly depressed compared to pretreatment at all levels of acute cholinesterase depression. The overall maximal ERG response demonstrated a trend of declining a-and b-wave amplitudes, which corresponded with the increased levels of cholinesterase depression, but these differences were not significant. The depression of the electroretinogram rod and cone amplitudes appeared to parallel plasma cholinesterase inhibition more closely than erythrocyte cholinesterase activity. Ocular tissue cholinesterase activity was significantly depressed in the retina (70%), cornea (60%) and dorsal rectus extraocular muscle (46%). Electroretinography may be a useful physiological tool for evaluating the ocular toxicity of certain chemicals or pharmaceuticals associated with cholinesterase biomarker activity.Abbreviations AChE acetylcholinesterase - Amp amplitude - BuChE butyrylcholinesterase - C _p plasma level - C _ss steady-state plasma concentration - D _L loading dose - e ^–kt the rate of elimination over time (t) - ERG electroretinogram - k elimination rate constant - Lat latency - MBW metabolic body weight - O₁–O₅ consecutive oscillatory potential wavelets - PreTx pretreatment - R rate of infusion - R _Inf rate of infusion - V _d volume of distribution     

Efficacy of daily amitraz on generalised demodicosis in dogs

Fifty dogs with generalised demodicosis were treated with daily applications of 0·125 per cent amitraz solution over half the body. This was applied once a day, alternating the body half treated. Nine dogs were lost to follow-up; the remaining dogs were classified as either a success (25 dogs, 61 per cent) or a failure (16 dogs, 39 per cent) according to their response to treatment. Eight of the failures were due to persistent demodicosis and eight relapsed within one year after treatment. All eight of the relapsed dogs were cured after a second course of daily amitraz treatment. For the 25 dogs considered treatment successes, the median duration of treatment was 6·5 weeks (range, three weeks to nine months), and the median interval from completion of treatment to last post treatment evaluation was 3·4 years (range, two to four-and-a-half-years). Including the eight dogs that were cured after retreatment, the daily amitraz applications were curative in 33 of 41 dogs (80 per cent) with generalised demodicosis.     

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

Jejunal Intussusception: A Complication of Functional End-to-End Stapled Anastomoses in Two Ponies

Jejunojejunal intussusception occurred after jejunal resection and stapled functional end-to-end anastomosis in two pony mares. In both mares, the lead point of the intussusception was the stapled functional end-to-end (FEE) anastomosis. The stapled free ends of jejunum were oversewn with an inverting suture pattern. A possible explanation for development of the intussusception was the acute angle created in the intestine by the FEE anastomsis. This angulation may have impaired flow of ingesta causing motility changes that predisposed the site to intussusception. Because the oversewn blind intestinal ends acted as the lead point for formation of the intussusception, it may be inadvisable to oversew the stapled anastomotic ends.     

Aggregate testing for the evaluation of Johne's disease herd status

This paper examines methods for evaluating herd Johne's disease status that could be used in a survey of the cattle industry. Emphasis is placed on aggregate testing, a process whereby a random sample of cattle from a herd is assessed using an imperfect test, such as an ELISA for detecting antibody in serum. Important aggregate test parameters discussed include: sample size, herd-level sensitivity, herd-level specificity, the number of reactors used for declaring a positive herd result, and the expected within-herd prevalence of disease. Aggregate testing may be useful for several livestock diseases. However, problems arise when it is applied to Johne's disease because of the poor sensitivity of the available diagnostic tests, the low within herd prevalence of infection, and clustering of false positives within a herd.