Use of enzyme immunoassay and reverse-phase high-performance liquid chromatography to detect and confirm identity of dexamethasone in equine blood.

An enzyme immunoassay (EIA) was developed for detection of dexamethasone in equine blood. Dexamethasone 21-hemisuccinate-bovine serum albumin was used for immunization of rabbits, and prednisolone 21-hemisuccinate-horseradish peroxidase was used as enzyme conjugate. The assay had sensitivity in the low-picogram range (detection limit, 0.3 pg/well, 50% inhibition of binding at 4.5 +/- 0.7 pg/well). Apart from cortisol, which was recognized by the antiserum at concentration > 8.5 ng/ml, the dexamethasone antiserum failed to interfere with endogenous steroids, but cross-reacted with triamcinolone, flumethasone, and betamethasone. Thus, the antiserum was used to perform simultaneous screening for these synthetic glucocorticoids and to confirm their identity by combining reverse-phase high-performance liquid chromatography (RP-HPLC) and EIA. The immunoreactivity obtained by direct serum measurements was characterized by means of 2 independent RP-HPLC systems. Serum extracts were submitted to RP-HPLC systems I and II, and the fractions were tested by EIA. Immunoreactive peaks were identified by comparing their retention time with that of the standard glucocorticoids used for calibration. Coinjection of an internal standard (methylprednisolone) in RP-HPLC system II yielded reproducible relative retention times. The effectiveness of the test system was evaluated, using blood from a horse treated with commonly used veterinary preparations of dexamethasone. Administration of the free alcohol of dexamethasone and of dexamethasone 21-trioxaundecanoate, both given IV, was detected, and the identity of each was confirmed for up to 48 hours. Intramuscular administration of dexamethasone 21-isonicotinate was continued for at least 14 days after injection of a therapeutic dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

牦牛皮蝇蛆病低残留防治技术研究

应用埃普利诺菌素注射剂采用常规与微量给药技术,进行对牦牛皮蝇蛆病的防治试验,10月下旬给药,翌年3、5月份两次触摸检查牛背部皮下瘤疱和皮肤虫孔,并设阳性对照组,评价两种给药技术对牦牛皮蝇蛆病的防治效果。结果:两次检查阳性对照组平均感染率为39.15%,平均感染强度6.75(1~17)个;埃普利诺菌素注射剂常规剂量100、200、300μg/kg试验组牦牛两次检查平均治愈率和驱虫率均达100.0%;埃普利诺菌素注射剂微量10、20、30μg/kg防治组平均治愈率分别为86.3%、94.2%和100.0%,驱虫率分别为79.7%、93.2和100.0%。使用安全。给泌乳牦牛皮下注射埃普利诺菌素注射液0.2mg/kg后54.00h,牛奶中的埃普利诺菌素浓度达到峰值7.38±2.61ng/m L,低于美国(12 ng/m L)和欧盟(20ng/m L)规定的埃普利诺菌素在牛奶中的最高残留限量标准,不需休药期;皮下注射0.4mg/kg后56.00±26.31h,牛奶中的皮下注射浓度达到峰值6.98±2.98ng/m L,低于欧盟规定(20ng/m L),不需休药期,高于美国规定(12ng/m L),需休药期。适合当前家畜健康养殖中对牦牛寄生虫病防治的需要。     

The effectiveness of cholecalciferol and flumethasone for the prevention of hypocalcemic parturient paresis in dairy cows]

Investigations on the efficacy of high doses of cholecalciferol and flumethasone for prophylaxis of hypocalcemic milk fever were performed in dairy cows. Only one cow in the group of 25 treated animals diseased by milk fever, but 5 of 25 control animals showed signs of hypocalcemia. A placenta retention was observed in three treated animals and in four control animals. The results show that the additional application of flumethasone for birth induction after the injection of vitamin D3 was unchanged.     

Fenbendazole-related drug residues in milk from treated dairy cows

Oral administration of [¹⁴C] fenbendazole (FBZ) at a dose of 5.Omg/kg leads to the presence of radiolabel in the milk of lactating dairy cows. However, the maximum mean concentration of total FBZ equivalents quantitated to one-third of the recommended safe concentration in milk (1.67 μg/mL). The label is equally distributed to the fat and aqueous portions of the milk. The maximum level, in general, is attained approximately 24-36 h after drug administration, with the highest levels ranging from 24 to 48 h after administration. The residues rapidly deplete, attaining levels of 10-20ng/mL by day 5, and are essentially undetectable by radiolabel monitoring by day 6. Extraction of the milk by matrix solid phase dispersion indicated that the label was distributed between traces of the parent drug, FBZ, and predominantly, the FBZ sulphoxide (SO) and sulphone (SO₂) metabolites. No other radiolabelled peaks were observed. Based on these data the metabolites of FBZ, FBZ-sulphone and FBZ-sulphoxide, could be used as marker residues for monitoring the administration of FBZ to lactating dairy cows.     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Feline plasma cortisol (hydrocortisone) measured by radioimmunoassay.

Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats.     

Glucose and cortisol concentrations in cows treated with a slowly-absorbed betamethasone suspension

A slowly-absorbed aqueous suspension of betamethasone, intended for use in the induction;of parturition, was administered to 10 cows. Each cow received 2ml (mean individual dose, 44.4 +/- 0.5microg/kg) by subcutaneous injection. Plasma samples were collected on six occasions over a seven-day period before treatment and on 21 occasions over a 29 day period after treatment. The mean concentration of betamethasone in plasma, as measured by radioimmunoassay, peaked at 0.6ng/ml24 hours after injection and was detectable for four days. Depression of the endogenous cortisol levels, as recorded with other long-acting synthetic glucocorticoids, was observed with this preparation of betamethasone. Plasma glucose was significantly elevated for eight days after betamethasone administration.     

Carprofen in veterinary medicine. I. Plasma disposition, milk excretion and tolerance in milk-producing cows

Carprofen, a non-steroidal anti-inflammatory drug (NSAID), was injected intravenously in six cows after calving, either as a single or a daily dose of 0.7 mg/kg for five days. Carprofen was well tolerated by the cows at this dose rate, the milk production and biochemical variables remaining within the normal ranges. The plasma elimination half-life of carprofen ranged from 44.5 to 64.6 h after repeated daily injections. These values are longer than those reported for other NSAIDs used in veterinary medicine, e.g. flunixin and phenylbutazone. The volume of distribution and the clearance values calculated after a single intravenous injection amounted to 0.09 l/kg and 9.0 ml/min. The concentration of carprofen in milk collected twice daily (morning and evening) was, in general, below the sensitivity limit of the analytical method (25 ng/ml) up to five days after the last carprofen injection; the concentration of carprofen reached about 30 ng/ml in only a few milk samples collected after the fourth or fifth injection. This indicates that carprofen is poorly excreted in the milk.     

Concentrations of buparvaquone in milk and tissue of dairy cows

AIM: To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk.

METHODS: Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5?mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018?mg/kg for muscle and 0.00023?mg/L for milk. Concentrations of buparvaquone in milk and tissues were log₁₀-transformed for analysis using multivariate models.

RESULTS: In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3).

Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows.

CONCLUSIONS: Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.     

Bioavailability, pharmacokinetics, and tissue distribution of 14C homidium after parenteral administration to Boran cattle

The absorption, distribution and elimination characteristics of ¹⁴C homidium have been described in non-infected and Trypanosoma congolense -infected cattle treated with ¹⁴C homidium chloride by either intramuscular (i.m.) or intravenous (i.v.) injection at a dose level of 1 mg/kg body weight. Results show that the mean (± SD) elimination of the drug from plasma followed a biexponential process, with half-lives of 0.084 ± 0.006 h and 97.66 ± 16.28 h for the distribution and elimination phases after intravenous injection, respectively. Bioavailability of the intramuscular dose was 62.5% and 57.8% in non-infected and trypanosome-infected cattle, respectively. Absorption was rapid, with a t _max of 15 min and a mean C _max (± SD) of 268.4 ± 4.09 ng/mL following the intramuscular dose in non-infected cattle. The major route of excretion was via faeces. Approximately 90% of the total dose given to non-infected i.m.-treated cattle was excreted within 14 days. Following intramuscular administration of the drug, residues remained high in the major excretory organs, with the liver having concentrations of 1411 and 1199 ng/g after 14 and 28 days, respectively. Over the same period, the values in the kidneys were 649 and 448 ng/g. Concentrations in the liver 14 and 21 days following i.v. treatment were 2195 and 2454 ng/g, respectively. These results show that there was no significant difference in liver drug residues between 14 and 21 days, or 28 days depending on the treatment given, suggesting that once the drug is in this organ, it is released back into the circulation at an extremely slow rate.     

Some pharmacokinetic parameters of the trypanocidal drug homidium bromide in Friesian and Boran steers using an enzyme-linked immunosorbent assay (ELISA)

Pharmacokinetic studies on the trypanocidal drug homidium bromide using a competitive enzyme immunoassay (detection limit 0.1 ng/mL) are reported for non-infected Friesian and Boran steers following treatment with homidium bromide at a dose of 1.0 mg/kg b.w. Following intravenous (i.v.) treatment of Friesian steers (n = 5), the mean serum drug concentrations were 31.9 +/- 2.1 and 3.9 +/- 0.4 ng/mL at 1 and 24 h, respectively. The decline in serum drug concentration was tri-exponential with half-lives of 0.064 +/- 0.037 h for t1/2 alpha, 7.17 +/- 1.87 h for t1/2 beta and 106.3 +/- 6.6 h for t1/2 gamma for distribution and elimination phases 1 and 2, respectively. Drug was detectable in serum for 17 days following treatment. The mean residence time (MRT) was 63.4 +/- 7.5 h. Following intramuscular (i.m.) treatment of Friesian steers (n = 5), the drug concentration at 1 h after treatment was 72.5 +/- 2.2 ng/mL. This declined to 9.8 +/- 1.8 ng/mL at 24 h. Low concentrations of between 0.1 and 0.3 ng/mL remained in circulation for up to 90 days post-treatment. Following intramuscular treatment of Boran steers (n = 5), the mean serum drug concentration at 1 h after treatment was 112.1 +/- 40.3 ng/mL. By 24 h after treatment, the concentration had fallen to 13.0 +/- 3.3 ng/mL. Thereafter, the serum drug concentration-versus-time profile and the pharmacokinetic parameters obtained following non-compartmental analysis were similar to those obtained following intramuscular treatment of Friesian steers.     

Canine plasma cortisol (hydrocortisone) measured by radioimmunoassay: clinical absence of diurnal variation and results of ACTH stimulation and dexamethasone suppression tests.

A radioimmunoassay for plasma cortisol (hydrocortisone) was developed and validated for sensitivity, specificity, accuracy, precision, and parallelism. Steroids were extracted with ethyl ether, and cortisol was purified by gel column chromatography prior to assay. [1,2-3H] cortisol and a commercially available sheep antibody to cortisol-21-hemisuccinate were used. Free steriods were separated from bound steroids by centrifugation after adsorption to dextran-coated charcoal. Plasma cortisol was measured by this technique in 6 normal dogs. Circadian rhythm of cortisol secretion was not detected in samples obtained by venipuncture at 8 different hours on 3 separate days, suggesting that adrenal function tests may be started in clinical patients at any time of day. Resting plasma cortisol concentrations averaged 19.4+/-3.0 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 77.5 ng/ml. Of 144 canine plasma samples, 95% contained less than 50 ng of cortisol/ml. Intramuscular injection of 2.2 units of adrenocorticotropic hormone/kg of body weight caused detectable increase in plasma cortisol concentrations; maximum response (68.3 to 111.6 ng/ml) occurred 1 to 2 hours after injection. Oral administration of dexamethasone suppressed plasma cortisol to nondetectable concentrations for 32 hours in all 6 dogs.     

Residues from long-acting antimicrobial preparations in injection sites in cattle

Objective To investigate tissue residues of two longacting oxytetracycline (OTC) preparations in cattle.
Design A randomised drug residue trial.  

Animals

Two hundred and forty beef cattle in 24 groups of ten.
Procedure Two blind-coded 200 mg/mL OTC preparations were used in five treatment regimens of various combinations of injection sites (from one to five) and administrations (one or two). Five cattle from each group were slaughtered at 21, 30 and 60 days after injection and the injection site, urine, kidney and diaphragm muscle analysed for residues.
Results The OTC concentration exceeded the maximum residue limit in kidney in animals slaughtered 21 days after treatment, which is the prescribed withholding period. Concentration at the injection site was much greater than the maximum residue limit 30 days post-treatment, but not 45 days post-treatment. The residue was smaller when OTC had been injected in multiple sites. There was no difference between the two OTC preparations.
Conclusion A review of the maximum injection volume, site of injection and the withholding period is needed for long-acting OTC formulations.     

Erfahrungen mit verschiedenen Anwendungsformen eines neuen Gestagens (Sa. 45.249) zur Brunstinduktion bei stillbriinstigen Milchkühen and Verlaufsbeobachtungen mit dem Milchprogesterontest

Inhalt Zur Brunstinduktion bei stillbrünstigen Milchkühen eignete sich eine 10-tägige orale Behandlung mit 10 mg pro Tier and Tag eines neuen Gestagens: Sa 45.249. Innerhalb von 9 Tagen waren 19 von 20 Tieren brünstig (10 Tiere mit deutlicher, 7 Tiere mit schwacher Brunst). 11 Tiere konzipierten auf die Besamung bei der ersten Brunst. Insgesamt wurden 16 von 20 Tieren nach durchschnittlich 17,4 Tagen mit einem Besamungsindex von 1,3 tragend. Eine zweimalige Behandlung mit 40 mg (1. Behandlung i. m., 2. Behandlung 72 Stunden später oral) erbrachte weniger günstige Resultate bezüglich Brunstinduktion (17 Tiere von 25 Tieren in 9 Tagen), Brunstintensität (6 Tiere mit deutlicher, 11 Tiere mit schwacher Brunst) and Erstkonzeptionsrate (5 Tiere von 25 Tieren). Insgesamt wurden bei zweimaliger Applikation 21 von 25 Tieren nach durchschnittlich 47,5 Tagen mit einem Besamungsindex von 2,2 tragend. Progesteronwerte and Ovarialpalpationsbefund stimmten in 13,3 % der Fälle nicht überein. Bei 4 Tieren ohne palpierbare Funktionsgebilde zeigten 3 Progesteronwerte, die auf luteale Funktionen hinwiesen, während bei 3 Tieren mit palpierbaren Corpora lutea Progesteronbasiswerte vorlagen. Bei einem Tier stiegen nach Konzeption die Milchprogesteronwerte nur langsam an and erreichten nur 2,6 ng/ml am 6. and 10,7 ng/ml am 8. Tag der Gravidität. Contents Experiences with differing dosage forms of a novel progestin (Sa 45.249) for the induction of estrus in dairy cows with silent heat and simultaneous observations with the milk progesterone test. Oral administration of a novel progestin, Sa 45.249, 10 mg/day for 10 days, was effective in inducing heat and fertility in 20 dairy cows with silent heat. Within 9 days after the last medication 19 of 20 animals were in heat (10 with significant, 9 with weak or questionable symptoms) and 11 animals conceived from a. i. at the first heat. A total of 16 out of 20 animals became pregnant after an average of 17,4 days and an a. i. index of 1,3. A treatment of only two drug applications, one i. m. injection of 40 mg and an oral administration 72 hrs later of another 40 mg of Sa 45.249 was less effective. Within 9 days, only 17 of 25 treated animals showed heat (6 with significant, 11 with weak symptoms), and only 5 of 25 animals bred conceived at the first heat after treatment. 21 of all animals treated became eventually pregnant, after an average of 47,5 days, and an a. i. index of 2,2. The results from rectal ovarian palpation and milk progesterone values did not concur in 13,3 %. In 4 animals with no signs of functional activity at both ovaries, 3 showed progesterone values in milk indicative of luteal activities, while in 3 animals with corpora lutea progesterone values were at the baseline, below any level of c. 1. activity. In one animal progesterone values in milk after conception rose very slowly and reached only 2,6 ng/ml and 10,7 ng/ml at days 6 and 8 of gestation, respectively.     

Effect of milk fraction on concentrations of cephapirin and desacetylcephapirin in bovine milk after intramammary infusion of cephapirin sodium

Clinical mastitis in dairy cows is commonly treated with intramammary (IMM) antimicrobial agents. Pharmacokinetic data are used to design treatment regimens and determine withholding times. In some pharmacokinetic studies, investigators measure antimicrobial concentrations in foremilk, whereas in others, they use bucket milk or do not specify the milk fraction sampled. Our objective was to compare antimicrobial concentrations in foremilk, bucket milk, and strippings after IMM treatment of six healthy Holsteins. One mammary gland/cow was infused with 200 mg of cephapirin (CEPH) after each of the two milkings, using different milking frequencies and treatment intervals in a randomized crossover design. Treated glands were sampled at the first milking following each infusion. Antimicrobial concentrations in milk were measured using HPLC/MS/MS. CEPH concentration was higher in foremilk (geometric mean 44.2 μg/mL) than in bucket milk (15.7 μg/mL) or strippings (18.5 μg/mL), as it was true for desacetylcephapirin (DAC) (59.5, 23.0, and 30.2 μg/mL, respectively). This finding, which was based on milk samples collected at the first milking after IMM infusion, suggests that pharmacokinetic data based on drug concentrations in foremilk may be misleading. Strippings were more representative of bucket milk than foremilk. The relationship between milk fraction and antimicrobial concentration should be investigated for other IMM antimicrobial agents. Meanwhile, it is essential that pharmacokinetic and residue studies report the fraction of milk that was analyzed.     

Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs.

Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites.     

The bovine pituitary-adrenocortical axis and milk yield

A review is given of the available literature concerning the relationship between the bovine pituitary-adrenocortical axis and milk yield in dairy cattle. A severe drop in milk yield (more than 50%) can be induced by a single or repeated intramuscular injection of at least 200 IU ACTH or by a single intramuscular injection of 14.6 mg dexamethasone. Sixty minutes after an intravenous injection, both 200 IU ACTH and 100 mg cortisol are equivalent to a plasma cortisol concentration of at least 31 ng/ml. Thus the decrease in milk yield after an intramuscular injection of more than 200 IU ACTH can hardly be induced by cortisol only. The fact that bovine plasma hardly binds any dexamethasone, in sharp contrast with bovine mammary epithelial tissue, is a possible explanation of the special part which dexamethasone plays in milk yield.     

Adrenocortical function testing in dairy cows and its effect on milk yield.

Administration of 6IU synthetic ACTH1-24 intravenously to six Holstein-Friesian cows resulted in a cortisol peak concentration after 1 hour of 148 +/- 34.2 ng/ml. Basal plasma cortisol concentration (4.84 +/- 0.83 ng/ml) was reached 5 hours after ACTH injection. Until 7 days after ACTH administration no effect on milk yield was recorded. So it is concluded that a dose of 6 IU ACTH1-24 is sufficient for a conspicuous release of cortisol without any alteration in milk production. This dose can be used as a standard test for the evaluation of adrenocortical function in lactating cows when administered intravenously at 9 a.m. and when plasma samples for cortisol assay are collected just prior to administration and at 10 a.m.     

Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat

The suppressive effects of three different low dosages of dexamethasone (5, 10 and 15 micrograms kg-1) on serum cortisol concentrations were evaluated in 10 normal cats. On four different days, serum was collected before and at two, four, six and eight hours after the intravenous administration of saline or dexamethasone. Following the administration of saline, no significant difference in mean serum cortisol concentrations was noted between the basal or postinjection values. In contrast, mean serum cortisol concentrations decreased significantly (P less than 0.05) by two hours and remained significantly below mean basal values eight hours after injection of all three dosages of dexamethasone. The degree of cortisol suppression became progressively greater as the dosages of dexamethasone were increased. After administration of the highest dose of dexamethasone (15 micrograms kg-1), serum cortisol decreased to below 5 ng ml-1 by two to four hours and remained suppressed (under 5 ng ml-1) eight hours after injection in all cats. In contrast, two of the 10 cats showed a slight escape from cortisol suppression by eight hours after injection of dexamethasone at the dosage of 10 micrograms kg-1, whereas a dosage of 5 micrograms kg-1 failed to suppress cortisol concentrations below 10 ng ml-1 at any of the sampling times in one cat and was associated with increasing serum cortisol concentrations at eight hours after injection in three cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tilmicosin antibacterial activity and pharmacokinetics in cows

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 μg/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 μg/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 μg/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t_1/2β values for 3 cows were 46.4. 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t_1/2el) was 4.18 ± 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 μg/mL were found in the secretion for 8–9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.