Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

Summary

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vie 1.621/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half‐lives were in the range between 11.6 and 17.2 hrs.

The mean OTC binding to plasma proteins was 75.5 ± 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 μg/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 ± 0.06 μg/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 μg/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 μg/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 ± 0.67%, and after medicated pelleted feed administration 3.69 ± 0.8%.

The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P< 0.005), being 3–5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Age difference in pharmacokinetics of an amoxycillin trihydrate‐15% formulation administered intramuscularly to ruminants

Summary

Intramuscular administration of an amoxycillin trihydrate‐15% formulation to three groups of animals revealed in preruminant calves (age 3–4 weeks) significant higher plasma peak drug concentrations and shorter biological half‐lives than in 5‐month‐old ruminant calves and dairy cows. Differences in pharmacokinetics were related to age‐difference in drug absorption capability at the injection site regarding the formulation.     

Pharmacokinetics of ciprofloxacin in carp,African catfish and rainbow trout

Summary

The plasma disposition of ciprofloxacin was studied in carp, African catfish and trout after intravenous (IV) and intramuscular (IM) administration at a dose rate of 15 mg/ kg. Pharmacokinetic analysis of IV data showed that ciprofloxacin was well distributed (distribution volume V area): 3.08 ‐ 5.59 litre/kg) and exhibited a similar elimination half‐life of about 14 h in these 3 fish species. After IM administration to carp and trout a rapid absorption was noticed; the maximum ciprofloxacin plasma concentrations (mean: 3.49 and 2.37 pg/ml, respectively), were achieved within I h after injection. At the dose level applied, ciprofloxacin has potential therapeutic value for 2–5 days especially against gram‐negative bacterial fish pathogens.     

The acetylation‐deacetylation equilibrium of sulfadimidine in ruminant calves

Plasma disappearance curves of sulfadimidine (SDM) in calves show at high doses a pattern resembling that of capacity‐limited elimination. The half‐life of the first part of the elimination phase of SDM when administered at high doses ranged between 6.4 and 11.5 h, while that of the terminal end of the plasma concentration‐time curves was similar to that obtained at a low level application, ranging between 2.5 and 6.0 h.

The percentage of N₄‐acetylsulfadimidine (N₄‐SDM) in plasma was low, viz. 2.2 to 5.8% of the total sulfadimidine concentration measured. The acetylation‐deacetylation equilibrium was established within 3 h p.i. The N₄‐SDM plasma concentration‐time curves were parallel to those of SDM beyond 3 h p.i. At high doses (66–235 mg/kg) the percentage of N₄‐SDM was slightly higher than that found at the low dose level.

A small proportion of N₄‐acetylsulfadimidine, injected as the parent compound, was deacetylated to SDM. The intrinsic elimination half‐life of N₄‐SDM was 0.9 h. It may be concluded that ultra‐trace concentrations of N₄‐SDM, left in edible tissues of ruminants at slaughter, have in case of negative sulfonamide‐sensitive bioassays no significance for the public health.     

Residues of sulphadimidine and its metabolites in eggs following oral sulphadimidine medication of hens

Summary

The depletion of sulphadimidine(SDM) and its N₄‐acetyl and hydroxy metabolites was studied in eggs laid by hens after administration of either a single or multiple oral dosages of 100 mg SDM/kg. During medication and until I day after the last dose, the SDM and its metabolite concentrations in the egg white exceeded those in the egg yolk and reflected the plasma levels. In the period starting 2 days after the (last) dosage, the SDM concentration in the yolk became higher than in the egg white, and the drug depletion curves ran parallel. The mean maximum amount of SDM found in the whole egg was 1500 μg after a single and 1280 pg after multiple dosage. In eggs, traces of the N₄‐acetyl and 6‐methylhydroxy metabolites could be detected (mainly in the egg white), and their concentrations were approximately 40 times lower than those of the parent drug. A highly significant correlation (P< 0.005) was found between the development stage of the oöcyte at the time of (last) medication and the amount of SDM found in the egg that developed from it. A period of 7 or 8 days after the (last) dosage of 100 mg SDM/kg/day is required to obtain SDM levels below 0.1 μg/g egg.     

Comparative pharmacokinetics and bioavailability of eight parenteral oxytetracycline‐10% formulations in dairy cows

Summary

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%‐formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half‐life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4. 1 μg/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 μg/ml, were achieved 12 to 24 h p. i. The OTC milk concentration‐time profile ran parallel to the OTC plasma concentration‐time profile.

After intravenous administration the time for the appearance of OTC in milk was shorter (1–2 hours p.i.), the peak milk OTC concentration was higher (1.7–1.9 μg/ml) and achieved earlier (6–8 h p.i.). and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability.

The plasma and milk protein binding for OTC was respectively 71.7± 7.4% and 84.8 ± 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.     

Dose dependent disposition of sulphadimidine and of its N4‐acetyl and hydroxy metabolites in plasma and milk of dairy cows

Summary

The disposition of sulphadimidine (SDM) and of its N₄‐acetyl (N₄‐SDM) and two hydroxyl metabolites, 6‐hydroxymethyl‐ (SCH₂OH) and 5‐hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine‐33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH₂OH. The metabolite percentages, the final plasma elimination half‐lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk.

At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 μg/ml, a capacity limited metabolism of SDM to SCH₂OH was noticed, viz, asteady state concentration of SCH₂OH and a biphasic elimination pattern for SDM and SCH,OH in plasma and milk.

The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH₂OH, SOH, and N₄‐SDM were: 0.69, 0.22, 020, and 0.63, respectively.

The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose.

A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 μg/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.     

Necrotising fasciitis in a bull due to infection with Arcanobacterium haemolyticum

Abstract

CASE HISTORY: A 2-year-old Hereford bull was lame for one week before becoming recumbent.

CLINICAL AND PATHOLOGICAL FINDINGS: The scrotum and ventral perineal region were cold and blackened caudally. The semimembranosus and semitendinosus muscles were firm on palpation. The bull was subject to euthanasia, and necropsy revealed that the skin and S/C tissues of the caudal half of the scrotum were grey and necrotic. The caudal and distal aspects of the semimembranosus and semitendinosus muscles were grey and necrotic to a depth of approximately 15 cm, and these changes appeared to track along fascial planes. The tissue had an offensive smell, and large amounts of flocculent, watery, brown fluid and some gas were present. Histology of affected muscle and S/C tissues revealed coagulative necrosis, with oedema and large numbers of bacteria that were predominantly Gram-positive rods. Adjacent blood vessels contained thrombi while the epidermis overlying the affected areas appeared diffusely necrotic, suggesting infarction. Culture of the fluid yielded a pure growth of Arcanobacterium spp., which was identified as Arcanobacterium haemolyticum, using an API Coryne biochemical test strip.

DIAGNOSIS: Necrotising fasciitis and myositis due to Arcanobacterium haemolyticum.

CLINICAL RELEVANCE: Arcanobacterium haemolyticum has not previously been reported as a cause of necrotising fasciitis in any species. Necrotising fasciitis is probably an under-reported condition in cattle due to its clinical similarity to clostridial disease.     

Veterinary dairy herd fertility service provision in seasonal and non-seasonal dairy industries - a comparison

The decline in dairy herd fertility internationally has highlighted the limited impact of traditional veterinary approaches to bovine fertility management. Three questionnaire surveys were conducted at buiatrics conferences attended by veterinary practitioners on veterinary dairy herd fertility services (HFS) in countries with a seasonal (Ireland, 47 respondents) and non-seasonal breeding model (The Netherlands, 44 respondents and Portugal, 31 respondents). Of the 122 respondents, 73 (60%) provided a HFS and 49 (40%) did not. The majority (76%) of all practitioners who responded stated that bovine fertility had declined in their practice clients' herds with inadequate cow management, inadequate nutrition and increased milk yield as the most important putative causes. The type of clients who adopted a herd fertility service were deemed more educated than average (70% of respondents), and/or had fertility problems (58%) and/or large herds (53%). The main components of this service were routine postpartum examinations (95% of respondents), fertility records analysis (75%) and ultrasound pregnancy examinations (69%). The number of planned visits per annum varied between an average of four in Ireland, where breeding is seasonal, and 23 in Portugal, where breeding is year-round. The benefits to both the practitioner and their clients from running a HFS were cited as better fertility, financial rewards and job satisfaction. For practitioners who did not run a HFS the main reasons given were no client demand (55%) and lack of fertility records (33%). Better economic evidence to convince clients of the cost-benefit of such a service was seen as a major constraint to adoption of this service by 67% of practitioners.     

Comparative imaging of European eels (Anguilla anguilla) for the evaluation of swimbladder nematode (Anguillicoloides crassus) infestation

This study compares diagnostic imaging tools in detecting the parasitic swimbladder nematode Anguillicoloides crassus in Anguilla anguilla (L.) and focuses on ultrasound in an attempt to develop a non‐destructive, field diagnostic test. Ultrasound use could allow the parasite to be diagnosed without decreasing the number of critically endangered European eels through post‐mortem. In the preliminary study, eels were examined with computed radiography, computed tomography, magnetic resonance imaging, 14 MHz high‐end ultrasound and 5 MHz low‐end portable ultrasound, and the results were compared with post‐mortem findings. This ultrasound scanning technique did not produce any promising results. A second batch of eels was examined using the same high‐end and low‐end ultrasounds, but employing a different scanning technique and comparing the results with post‐mortem. This second study, scanning along the midline from below, allowed for the detection of anomalies associated with moderately infected animals. None of the eels used in this study were severely infected; thus, no conclusions can be made regarding the use of ultrasound in those animals. Overall, it was found that none of the techniques were useful in diagnosing mildly infected individuals; therefore, no single diagnostic imaging tool is sensitive enough to replace post‐mortem for definite diagnosis.