Slow release bolus for small ruminants: in vitro release of tetracycline compared with serum concentrations of the antibiotic in sheep.

Two formulations of slow release boluses for small ruminants containing tetracycline hydrochloride in a compressed form were investigated in vitro and in vivo in adult sheep. An in vitro dissolution test was used for the preliminary selection of the 2 boluses. It was shown that the non-cumulative kinetics of tetracycline release in vitro were predictive of the tetracycline serum levels in sheep treated orally with the 2 boluses. The maximum concentrations revealed by the in vitro and in vivo curves were obtained at almost the same Tmax and, in vivo, the therapeutic serum levels were maintained for about 5 days. It is concluded that an in vitro approach is of value in predicting the kinetic profiles of a long-acting tetracycline bolus in sheep.

[Pharmacological research on ophthalmic drug lamellae containing gentamycin sulfate in laboratory and agricultural animals]. / Niakoi farmakologichni izsledvaniia vurkhu ochni lekarstveni lameli, sudurzhashti gentamitsinov sulfat, pri laboratorni i selskostopanski zhivotni.

The in vitro and in vivo solubility of ocular drug lamellae, containing 1.5 and 3 mg gentamycin sulphate, was followed up. It was found that those that contained lower amount of the antibiotic disintegrated in the eyes of rabbits, lambs, and sheep for 30-40 minutes, while lamellae having 3 mg gentamycin disintegrated for 45-50 minutes. It is stated that such ocular lamellae are well tolerated by the conjunctiva of the animal species referred to. With the application of one lamella with 3 mg gentamycin sulphate therapeutic concentrations of the antibiotic in the lacrimal secretion are found up to the 24 th hour with cows, sheep, and lambs, and up to the 48h hour with rabbits.

[Chronic 90-day toxicity of apramycin in chickens]. / Prouchvane vurkhu khronichnata 90-dnevna toksichnost na apramitsina pri pileta.

Investigations were carried out on 72 2-day-old broilers, divided into four groups (one control group--27 broilers and 3 experimental groups--15 broilers in each), treated with apramycin sulphate (AS), which was added to the food in concentration 0, 330, 1000 and 1600 mg/kg (corresponding to 0, 50, 150 and 250 mg/kg m.), in the course of 90 days. It was established that dose of 50 mg/kg m. AS does not causes toxic activities. With doses of 50, 150 and 250 mg/kg m. AS causes reduction of the degree of the pseudo-eosinophilic cells and increase of the percentage of leucocytes--in range similar to the physiological variations, contributes to stimulate the growth and the feed conversion. With doses of 150 and 250 mg/kg m. AS causes reduction of the content of haemoglobin and reduction of the number of erythrocytes; causes dystrophic changes in the internal organs.

[Therapeutic effect and residues of a Gentavet preparation in chicks, piglets and calves]. / Lecheben efekt i ostatuchni veshtestva na preparata Gentavet pri pileta, praseta i teleta.

Studied were the therapeutic and prophylactic effects of the preparation Gentavet (containing gentamycin complex II) with pigs, birds and calves affected with colibacteriosis. It was found that in conc. 80,000 IU (0.08 g or 0.8 g) with the drinking water (1 lit.) given 14 days to birds lowered the mortality rate to a higher extent than Avimycin (containing oxitetracycline and neomycin). At the rate of 10,000 IU (0.01 g or 0.1 g) per kg body mass, orally, split in two for 24 h with newborn pigs Gentavet produced a very good prophylactic effect, and when used at a higher rate--16,000 IU (0.016 g or 0.16 g) per kg under the same conditions up to 90 per cent of the pigs with polyenteritis recovered. At 10,000 IU (0.01 g or 0.1 g) per kg body mass, orally, split in two for 24 h with newborn calves with colibacteriosis produced therapeutic and prophylactic effects. Gentamycin complex II residual amounts remained longest in the parenchymal tissue of the kidneys and liver. The withdrawal times in slaughtering birds, pigs, and calves treated with Gentavet should last from 30 to 46 days (31 days for birds, 46 days for pigs and calves of up to 100 kg, and 30 days for heifers of up to 400-500 kg). This period could be shortened 4 to 5 days if both kidneys and liver are to be eliminated after slaughter.

[Use of foaming and nonfoaming gentamycin tablets in treating cows with chronic endometritis]. / Prilozhenie na penoobrazuvashti i nepenoobrazuvashti tabletki ot gentamitsin za lekuvane na kravi s khronichen endometrit.

Biopharmaceutic and therapeutic investigations were carried out with foaming and nonfoaming gentamycin sulfate tablets. The experiments were conducted with a total of 100 cows affected with chronic inflammation of the uterus. Both types of tablets, containing 30,000 IU of gentamycin sulfate each were introduced into the uterus via Andreev's catheter, bimanually or by means of a vaginal speculum and Albrechtzen's clamp, at the rate of 10. Followed up were the serum levels, the excretion with the milk, and the content in the uterine secretion of gentamycin after using the tablets. There was no statistically significant difference in the serum levels of gentamycin as initiated by the two types of tablets. In milk the peak values reached 0.02 micrograms/cm3, and in uterine washings (with 15 cm3 isotonic solution of sodium chloride) the proper levels were established up to 74nd hour. Demonstrated was the therapeutic effect in the treatment of cows with chronic endometritis - 77.4 per cent with the use of foaming and 71.4 per cent with the use of nonfoaming tablets. There was also a rising trend with the conception rate in the treatment of sterile cows (otherwise having no signs of uterine inflammation) with the use of nonfoaming tablets of gentamycin sulfate at the rate of 5, introduced 24 hours after insemination.

[Trial of trimedin action on chickens]. / Izpitvane deistvieto na trimedina pri pileta.

Investigations were carried out with a total of 421 broiler birds (four-line Cornish X Plymouth Rock hydbrids) within the age range of 2 days to 5 weeks. Determined was the acute toxicity of the combination sulfadimidine (SDM) + trimetoprim (TMP)--5 + 1 and the water-soluble formula of trimedin following the intraingluvial introduction with week-old birds. LD50 of the combinations SDM+TMP (5+1) was 3980 mg/kg (2780: 5690), and that of trimedin was 2038 mg/kg body mass. The biologic half-life of SDM ranged from 4.77 to 5.34 h, and that of TMP--from 4.81 to 5.71 h at the intraingluvial introduction of the combination SDM+TMP (5+1) at the rate of 0.06 g/kg. Demonstrated were the therapeutic levels of SDM and TMP during the whole period (10 days) of treatment with the combination SDM+TMP (5+1) given with the feed in conc. 500 ppm or at the application of trimedin alone via the drinking water in conc. 0.05%. It was found that trimedin used for 10 days with the drinking water in conc. 0.05 per cent with broilers at the experimental infection with Salmonella gallinarum-pullorum protected about 40 per cent of the birds, the latter remaining, however, carriers of the infection.

[Pharmacological, toxicological, microbiological and pathohistological studies of gentamycin complex II]. / Farmakologichni, toksikologichni, mikrobiologichni i patokhistologichni prouchvaniia vurkhu gentamitsin kompleks II.

The acute toxicity was determined of the gentamycin complex II (GMC-II) for albino mice, containing gentamycin components in a varying ratio. The LD50 at intraperitoneal application was 347.7 mg/kg body mass, while at oral application it was 5,180 mg (4933 divided by 5439) mg/kg body mass. Histopathologically, (mice killed with high doses of GMC-II, given orally) there were diffuse hyperemia of the liver, parenchymal degeneration of the kidney tubuli epithelium, and edema and emphysema of the lungs. The local tolerance with regard to a 5 per cent solution of GMC-II applied to the conjunctiva of rabbits at twofold treatment proved to be good. Determined were the minimal inhibiting concentrations of 14 species of pathogenic organisms of great interest to veterinary medicine (Bacillus anthracis, Erysipelothrix insidiosa, Salmonella gallinarum, Escherichia coli, etc.). The antibacterial spectrum of GMC-II was similar to that of gentamycin sulphate, however, for some pathogenic organisms higher concentrations were required to produce and antimicrobial effect. Similarly to gentamycin sulphate GMC-II had limited absorbtion in the alimentary canal of clinically normal newborn pigs and of birds. At a high rate (0.05 g/kg body mass) GMC-II applied via the crop to birds it was found to maintain the lowest therapeutic concentration in the serum. At the rate of 0.012 (equal to 12000 IU) per kg of body mass for 24 hours GMC-II produced therapeutic effects in newborn pigs affected with colibacteriosis.

[Doxycycline hydrochloride administered in the drinking water to poultry]. / Doksitsiklinov khidrokhlorid, prilozhim s vodata za piene pri ptitsi.

Investigated were the acute toxicity, serum concentrations, and residual amounts of doxycycline in broiler chickens. It was found that the LD50 of doxycycline when applied via the crop to week-old broiler birds was 2500 mg/kg mass. The amount of 0.005 g/kg mass given orally to birds led to serum concentrations that on the eighteenth hour were found to drop up to subtherapeutic ones. When applied with the drinking water at the rate of 0.02 to 0.04 g l or kg feed it was well absorbed as early as the first hours. In such case the drug maintained therapeutic concentrations that were higher in the internal organs than those in the serum. The residual amounts of doxicycline hydrochloride when it was applied at 0.04 g/l of water or kg feed were found up to 48 h hour by the method of agar diffusion, using Bac. subtilis L2 as a test organism. The withdrawal time should amount to 72 hours.

[Tridoxin toxicity and tolerance in agricultural animals]. / Izsledvane vurkhu toksichnostta i ponosimostta ot selskostopanskite zhivotni na tridoksina.

It was found that LD50 of tridoxin (sulfadoxin-trimetoprim-5 + 1--State Economic Corporation Pharmachim) at i/m application to albino mica was 950 mg/kg, and of borgal (Hochst)--920 mg/kg. At oral application these values were 2650 and 2660 mg/kg, respectively. LD50 of tridoxin at i/m application to albino rats was 1075 mg/kg, and of borgal--1320 mg/kg; orally, these values were 3000 and 3260 mg/kg, respectively. When introduced into the crop of week-old broilers the LD50 values of fridoxin and borgal were 942 and 1670 mg/kg, respectively. The oral administration of tridoxin with the feed in 3 to 5 times higher amounts than was the therapeutic muscular dose to albino rats in the course of 30 days did not lead to clinical, clinical-and-biochemical, and histopathologic changes. The tolerance of tridoxin at a single i/m injection of a 5- times higher dose than the therapeutic one (0.075 g/kg) in the case of calves was good, with the exception of transient pain at the time of injection and shortly after that and the slight, transient slowing down of forestomach movements. The injection of amounts 3 and 5 times as high as the doses for pigs, sheep, and weaned lambs was tolerated well. The application to sheep was found to be more painful than in the case of calves and pigs.

[Retention and tolerance of the mammary gland of different drug forms of gentamycin in intramammary administration]. / Zadurzhane i ponosimost ot mlechnata zhleza na razlichni lekarstveni formi ot gentamitsin pri intramamarno prilagane.

Tested were various drug forms of gentamycin sulphate (based on polyethyleneglycol, oil, and water solution) with regard to the tolerance of the mammary gland in cows and ewes. It was found that the oil-based preparations were much better tolerated as against those based on polyethyleneglycol. The aqueous solution of gentamycin sulphate, introduced in higher doses (up to 1200000 IU per udder quarter) slightly irritate the mammary parenchyma of cows as demonstrated with the presence of blood cell elements passed into the milk. A preparation that contained gentamycin sulphate (100000 IU) and hydrocortisone acetate, 0.2 (oil base) applied singly to lactating cows in an amount of 10 g(one syringe) maintained concentrations in most of the animals up to the 4th day following treatment. In lactating sheep antibiotic concentrations in the milk persisted up to the 5 th day, while in sheep in a period of drying residual amounts were established in the course of more than 10 days.