Absorption of lincomycin through the respiratory pathways and its influence on alveolar macrophages after aerosol administration to chickens.

A concentration of 250 mg m-3 lincomycin was administered by aerosol to 40 chickens, weighing between 1900 and 2200 g. The birds were killed in groups of five at different intervals after dosing, and the trachea, lungs and blood serum were examined for antibiotic content by bioassay. The antibiotic was present at high levels in the trachea for one to 24 hours, and significant levels were present in the lungs and serum. Respiratory macrophages were obtained from the lungs and air sacs of the chickens by lavaging through the surgically prepared trachea with a paediatric urinary catheter. The macrophages were identified by morphology as round or slightly amorphous, refractile, frequently grannular cells; they phagocytosed Staphylococcus aureus 6538.

[Physicochemical and pharmacokinetic research on Pharmachim's thiabendazole]. / Fiziko-khimichni i farmakokinetichni prouchvaniia na tiabendazol "Farmakhim".

Studied was the preparation thiabendazole-Pharmachim (TBZ-Ph), produced by the Economic Corporation "Pharmachim". In some of the experiments TBZ-Ph was comparatively studied with the Merck & Sharp and Dom preparation (TBZ-MShD), Switzerland. It was found that the light absorption maximum of TBZ-Ph was at 302 nm. Thermostability studies revealed that the preparation was comparatively stable in the course of 6 months at room temperature and at 4 degrees and 40 degrees C. When stored in the form of 1 per cent medicated feed at room t degrees, 4 degrees, and 40 degrees C it showed no deviations as against the check samples over a period of 70 days. TBZ-Ph was shown to possess slight photosensitivity; it was not hygroscopic. In oral administration to sheep and pigs at the rate of 100 mg per kg body mass, in the form of a 10 per cent water suspension TBZ-Ph was absorbed through the gastro-intestinal membrane. It was retained in the blood serum of sheep up to the 24th hour. The preparation was shown to gain access to almost all viscera and striated muscles, persisting in them for some twenty days. Following the oral application in a dose of 100 mg/kg it reached the mammary gland of lactating ewes and was detected in the milk in maximum concentrations as early as the 3rd hour (5.8 to 12.3 ppm); in the course of the following hours concentrations dropped, and in individual animals the preparation was traced up to the 96th hour.

[Pharmacokinetic research on Pharmachem's lincomycin hydrochloride in pigs]. / Farmakokinetichni prouchvaniia na linkomitsinov khidrokhlorid "Farmakhim" pri praseta.

In the experiments lincomycin hydrochloride LMC "F" with activity 820 UI/mg was used. It was established that in pigs, 5% water solution of LMC "F", applied intramuscularly in doses of 5 and 10 mg/kg m. and internally in doses 50 and 100 mg/kg m., penetrates comparatively quickly in the blood serum, and yet in the first hour established maximal concentrations. Intramuscular injection of LMC "F" of pigs, in doses of 5 and 10 mg/kg m., creates bacteriostatic concentrations in the blood serum for 12 hours, regardless of the quantity of the dose, and applied internally has a longer duration of the retention. The biological half-life of LMC "F" after muscular application in pigs is accordingly 1.7 and 3.5 hours, and after internal application 2.3 and 2.8 hours. Applied a single time intramuscularly in pigs in doses of 5 and 10 mg/kg m., LMC "F" is resorbed from the place of application and after 3 hours is established in most high quantities in the kidney in the lungs, the liver, the bile and in the urine. Mainly it is extracted with the urine in high concentrations--about 190 mg/cm3 (on the 3-rd hour), after intramuscular injection in dose of 10 mg/kg m. The longest time the antibiotic remains in the lungs, the urine and in the bile (up to 96 hours).

[Pharmacokinetic research and the ultrastructural changes in the lungs of white rats after aerosol administration of a high dose of kanamycin sulfate]. / Farmakokinetichni prouchvaniia i ultrastrukturni promeni na belite drobove na beli plukhove sled aerozolno prilagane na visoka doza kanamitsinov sulfat.

Studied is kanamycin sulphate "Pharmachem", substance with activity 750 UI/mg, applied on albino rats in the form of water aerosol. The experiments are carried out in aerosol camera of flow-dynamic type with capacity 450 l at exchange of the air 60 l/min with aerosol apparatus of pneumatic type, for 10 min and staying in the aerosol cloud another 10 min. It is established that the kanamycin sulphate, after aerosol application on albino rats in dose of 50000 UI/m3, passes in the blood and is found out in the serum yet in the first hour (1.75 +/- 0.23 mg/cm3 serum). The maximal quantities of antibiotic are established in the first hour in the lungs (52.1 +/- 11.4 micrograms/g) and the antibiotic is detained in therapeutical concentrations for 240 h (0.1 +/- 0.03 micrograms/g). The content of the kanamycin in the kidneys is in the limits from 0.1 +/- 0.02 to 1.69 +/- 0.17 micrograms/g. At the electronic-microscopic tests of the lungs is observed hyperemia and destruction of the lamella corpuscles, which processes up to the 120th hour gradually calmed down.

[Use of a broth made of the subepidermal layer of pig skin as feed]. / Izpolzuvane na bul'on ot podepidermalen sloi na svinski kozhi kato furazh.

Studied was a broth received from the T. Dokov leather factory in Etropole, prepared of swine skin subepidermal layer (BSSS). As many as 28 samples of BSSS were studied with regard to crude protein, crude fats, and aldehyde and peroxide numbers. The tolerability of BSSS was tested on a total of 150 Wistar albino rats after storing at various temperatures. Studied were also 10 batches of BSSS in fresh state (up to the 24th hour after receiving from the factory) as well as at intervals of up to 10 days in air-tight condition, at temperatures of 4 to 8 degrees C; 18 to 20 degrees C; and 37 degrees C. BSSS was administered orally, undiluted, at the rate of 3 ml/100 g body mass. The subchronic toxicity of BSSS was examined with two species of animals--pigs and broiler birds. BSSS was found to contain 12.2 to 14 g% proteins and 12.57 to 42.0 g% fats. When stored at 37 degrees C in nonsterile conditions its shelf life is but 24 hours, and at 4 degrees C it can be kept up to 10 days. It was tolerated well by rats, birds, and pigs when offered in fresh state. When mixed with other feed it did not lower the appetite of animals and could replace about 25-30 per cent of the daily protein ration. This, in turn, did not lead to changes in the white and red blood cell counts and in the biochemical composition of blood nor to changes in the internal organs and the striated muscles.

[Toxicological and pharmacokinetic research on lincomycin hydrochloride in broiler chickens and layer hens]. / Toksikologichni i farmakokinetichni prouchvaniia na linkomitsinov khidrokhlorid pri pileta broileri i kokoshki.

Tested was the activity of linkomycin hydrochloride at the rate of 820 IU/mg. The LD50 of the preparation was found to exceed 12.0 g/kg body mass at intracrop application to broiler birds. When offered with the drinking water or the feed in amounts that were 3 to 5 times higher than the therapeutic ones for broilers in the course of 45 days it did not cause mortality nor induced changes in the white and red blood cell counts, in the total protein, and in the levels of urea, blood sugar, AlT, and AcT. Neither were there any structural changes in the internal organs. Upon the single intracrop treatment of broilers with linkomycin at 50 and 100 mg/kg most of the amount introduced was established in the blood serum at the second hour and up to the 6th and 8th hour, respectively. Studies on the effect of age on the serum concentrations at this route of introduction revealed that the preparation was absorbed at higher rates in the broilers than in the layers, while with the persistence of the levels there were no essential differences. At the single oral administration with broilers in amounts of 100 mg/kg linkomycin was chiefly retained in the kidneys, liver, and lungs as well in the content of the small and large intestines. At intracrop application to layers in doses of 100 mg/kg in the course of 7 days the antibiotic was excreted with the eggs at the time of treatment and in the course of 4 days later in bacteriostatic concentrations of 0.6-5.9 micrograms/cm3.

[Toxicological and clinical research on Pharmachim's levamisole]. / Toksikologichni i klinichni prouchvaniia na levamizol "Farmakhim".

Defined was the acute toxicity LD50 of a 7.5 per cent solution of the Levamizol-Pharmachim preparation following its subcutaneous application to albino mice and rats. Sheep and pigs were also injected subcutaneously with the same solution and their tolerance of the preparation was defined at rates of 7.5, 22.5, and 37.5 mg per kg body mass. Comparative clinical testing was carried out of the 7.5 per cent solution of Levamizol-Pharmachim and Nilverm (ICI, England) with regard to their action against sexually mature strongylates in sheep and against swine ascaridiasis and Esophagostomum infection. It was found that the subcutaneous injection of albino mice with a 7.5 per cent solution of the preparation at the rate of 90 mg/kg was in fact the LD50 dose with this route of application. In the case of albino rats LD50 turned out to be 120 mg/kg. Levamizol had good tolerance with adult swine and pigs at subcutaneous introduction in a dose of 7.5 mg/kg. Death cases were recorded with these animals with the use of 37.5 mg/kg, which was 5 times the ED50 dose. The preparation was shown to be suitable for both therapeutic and prophylactic worming of sheep and swine.

[Preclinical research on Pharmachim's ronidazole]. / Predklinichni izsledvaniia na ronidazol "Farmakhim".

Ronidazol-Pharmachim (RPh) in the form of 10 per cent water-soluble powder was studied in terms of resistance to various values of pH of the surrounding medium, acute toxicity, the species-specific tolerance of various mammals of it, its subchronic toxicity and residual amounts with pigs. The preparation was found to be stable in water solutions (pH 5.0 to 9.0) in the course of at least 96 hours, and in n HCl--for more than a month. At oral administration LD50 of RPh was 34000 mg (2982 divided by 3876) per kg for albino rats weighing 150-200 g. At intraperitoneal injection in the form of pure substance LD50 was 1500 mg (1320 divided by 1690) per kg. With pigs at single oral application at the rates of 20, 60, and 180 mg/kg (= 20-30 times the ED50) RPh was tolerated with no changes in the behaviour and appetite. When used with the drinking water at rates of 60, 180, and 300 ppm in the course of 30 days there was no unfavourable effect on the gain and the blood picture and no injury of the structure of viscera of pigs. In concentrations of 180 ppm it was shown to stimulate the growth of pigs. The withdrawal time with pigs given RPh with the drinking water was at least 72 hours after the preparation was offered last.

[Pharmacological and clinico-pharmacological studies of diazepam powder in suspensions]. / Farmakologichni i kliniko-farmakologichni prouchvaniia na diazepam-pulvis za suspenziia.

Studied was the preparation diazepam-pulvis for suspension (DPS) with regard to its tranquillizing and myorelaxing doses, inhibiting the aggression, and preventing the stress conditions in domestic animals and birds. It was established that at oral application to pigs at rates of 1 to 2 mg/kg body mass DPS produced a pronounced tranquillizing effect, while at 3 mg/kg it led to myorelaxation as well. In sheep tranquillizing effect was seen when amounts of 3 to 5 mg/kg body mass were used, and myorelaxation was achieved with 6.6 to 13.2 mg/kg. In male calves tranquillization was manifested after doses of 3 mg/kg body mass were applied. In hens the tranquillizing dose was found to be 3 mg/kg body mass, and the myorelaxing one--4 mg/kg; in cocks the respective doses were 5 and 7 mg/kg body mass. At the rate of 3 mg/kg body mass DPS was found to enhance the thiopental-sodium narcosis. When offered to pigs at 2 mg/kg body mass in admixture with the feed DPS led to tranquillization and suppression of the active and passive defense response. No full prevention of cannibalism could be achieved. The daily administration in the course of 30 days with the ration of bull-calves at the rate of 3 mg/kg body mass was shown to calm the animals under loose housing in boxes and affect favourably their weight gain. Admixed with the feed of cocks at 5 mg/kg DPS suppressed aggressiveness.

[Tolerance for tetraolean i.m. and the blood levels in agricultural animals]. / Ponosimost na tetraolean i. m. i kruvni niva pri selskostopanski zhivotni.

Studied was a drug formula of tetraolean for i/m application, containing tetracycline hydrochloride and oleandomycin phosphate in a 2:1 ratio, produced by the Antibiotic Works, Razgrad, and released in flasks of 500 mg and 1.0 g. It was followed up with regard to its tolerable serum concentrations for rabbits, calves, pigs, and horses. It was found that in therapeutic amounts tetraolean was well tolerated and did not lead to local and general disturbances. In higher doses it was found to form transient oedema in the site of injection. Intramuscularly, tetraolean was well absorbed in the site of application, and, according to the animal species, it developed proper plasmal therapeutic concentrations at the following rates: calves--20 mg/kg body mass at 12-hour intervals; pigs--10 mg/kg at 6-hr intervals, or 20 mg/kg at 12-hr intervals; horses--10 mg/kg at 12-hr intervals or 20 mg/kg at 24-hr intervals.

[Species-specific toxicity of arprinocid in mammals and birds]. / Niakoi prouchvaniia vurkhu vidovospetsifichnata toksichnost na arprinotsid pri bozainitsi i ptitsi.

Studied was the species-specific tolerance and the subchronic toxicity of the arprinocid coccidiostatic (9-/2-chloro-6-fluorophenylmethyl/9H-pirineamine) in the form of a 12% premix with trade mark Arpocox, Merk Sharp and Dohme Research Laboratories. It was found that at single oral application arprinocid led to the intoxication of broiler birds at 50 mg/kg, turkey poults-at up to 18 mg/kg, ducklings--up to 18 mg/kg, goslings--up to 6 mg/kg, calves--up to 10 mg/kg, lambs--up to 60 mg/kg, pigs--up to 30 mg/kg. The lethal dose for chickens was over 100 mg/kg, turkeys and duckling--30 mg/kg, and goslings--18 mg/kg. Arprinocid given with the feed to chicken broilers in conc. 60 ppm for 30 days did not lead to side effects. In conc. of 120 and especially 180 ppm there was retardation of growth with birds and inhibition of hemopoiesis. With pigs the preparation in conc. 60 to 180 ppm given with the feed had no effect on the growth and consumption of feeds; in 120 ppm and especially in 180 ppm it inhibited the hemo- and erythropoiesis. With chickens and pigs arprinocid in 180 ppm did not cause degenerative and inflammatory changes in the liver, kidneys, heart, spleen, testes, ovaria, adrenals, thyroid, and skeletal muscles.

[Toxicological evaluation of "Farmakhim" thiabendazole in mammals and birds]. / Toksikologichni prouchvaniia na tiabendazol "Farmakhim" pri bozainitsi i ptitsi.

Studied were the acute toxicity (albino mice and rats, chicken broilers), species specific tolerance (lambs, sheep, goats, pigs, calves, chicks, chickens), and subchronic toxicity (albino rats, pigs, pulets) of tiabendazole Pharmachim (TP). It was found that LD50 of TP at the oral application to albino mice, weighing 18-20 g was 2.7 g (2.14 divided by 3.40) per kg for albino rats weighing 120-200 g it proved technically undeterminable. For broilers at one month it was 4.0 g (2.54 divided by 6.28) per kg. LD50 of TP of the firm Merck Sharp and Dome for albino mice was 2.9 g (2.28 divided by 3.68), and for broilers -- 5.0 g (4.31 divided by 5.8) per kg. The lethal dose for lambs was 400 mg/kg, for sheep -- 800 mg/kg, for goats -- 500 mg/kg, and for calves -- 500 mg/kg. When treated with amounts of 450 and 850 mg/kg pigs vomited. The same was true of drugs when offered the preparation at the rate of 300 mg/Kg chicks and chickens tolerated amounts of 500 mg/kg. TP was well tolerated by pigs, rats, and pullets when given with the feed for 30 days in 0.1 per cent conc.; in 0.4% conc. (pigs), 0.5% (albino rats), 0.3% (pullets), and 1% (albino rats and pullets) led to the arrest of growth and rise of transaminases and urea in the blood serum (rats and pigs) and the adverse effect of the red blood picture (rats, pigs, and pullets). Histologically, there were vascular troubles and granular degeneration that predominated in the kidneys, and were more slightly expressed in the remaining parenchymal organs.

[Concentration and retention time of ampicillin trihydrate in the blood serum when used internally with ruminants]. / Kontsentratsiia i produlzhitelnost na zadurzhane na ampitsilin-trikhidrat v kruvniia serum pri vutreshno prilagane na prezhivni zhivotni.

Studied was the resorption of ampicillin-trihydrate in the digestive tract and its retention in the blood serum of lambs (at rates of 20, 30, and 50 mg/kg body weight), sheep (at rates of 50, and 70 mg/kg body weight), and calves (at rates of 30, 50, and 70 mg/kg b. w.) when applied in the form of a 10 per cent water sus ensior and gelatine capsules. It was found that the blood levels and the time of retention of ampicillin at its oral application to ruminants were directly correlated with the amount applied, the drug form of the antibiotic, and the age of the animals. The oral use with calves aged 15 days at the rates mentioned in the form of a water suspension diluted with milk led to peak concentrations at the second hour. In this case ampicillin-trihydrate was retained in the blood serum in the course of 12 hr regardless of the amount applied. The serum levels of the product in 2.5-month-old calves used at 50 and 70 mg/kg in the form of a water suspension were either traces or could not be defined at all, while in calves at the same age the milk-diluted ampicillin suspension in the doses referred to showed bacteriostatic concentrations.

[Routes of ampicillin elimination in agricultural animals]. / Prouchvaniia vurkhu niakoi ot putishtata za izluchvane na ampitsilina pri selskostopanski zhivotni.

Studied were ampicillin-Na and ampicillin-trihydrate of an 800 IU/mg activity. The first was applied in the form of aqueous solution, and the second--in the form of an aqueous suspension. It was found that i/m injection of ampicillin-trihydrate to sheep (10 and 25 mg/kg) and lambs (10 and 20 mg/kg) led to the elimination of the antibiotic via the urine in bacteriostatic concentrations for 48 hours, while the application of ampicillin-Na under the same conditions led to its elimination in the course of 24 hours. In lactating ewes ampicillin was eliminated through the milk secretion. At a single muscular injection to ewes at the rate of 25 mg/kg ampicillin-Na was eliminated via the milk in higher concentrations, reaching a peak volume at the fourth hour--0.75 mg/cm3, for a shorter period of time (up to the 14th hour) as compared to ampicillin-trihydrate (up to 24th hour) when used in the same dose. When applied to laying hens directly through the crop at 60 mg/kg in the course of six days it was excreted during treatment and two days later via the eggs in therapeutic concentrations.

[Ampicillin tolerance and content in the mammary gland of lactating cows and sheep]. / Ponosimost i zadurzhanie na ampitsilin v mlechnata zhleza na laktirashti kravi i ovtse.

Experiments were carried out with lactating cows and ewes consisting in the intramammary application of ampicillin-trihydrate with the use of syringe cannules, and with paraffin and vaselin as constituents. Cows were treated with 10 cm3 (500,000 IU) (in the respective quarter of the udder), and ewes--with one half of the syringe content. The milk of the treated animals was sampled prior to manipulation, at the 24th, the 48th, 72nd and 96th hour in order to follow up the time during which the antibiotic was retained in the milk as well as the changes in the cell content and the hydrogen ion concentration. It was found that ampicillin persisted in milk up to the 48th hour in therapeutic concentrations. At the 96th hour the milk proved free of the antibiotic in both cows and ewes and could be offered for consumption or technologic processing.

[Absorption and retention of ampicillin in calves and sheep]. / Vurkhu rezorbtsiiata i zadurzhaneto na ampitsilin pri teleta i ovtse.

Ampicillin-sodium and ampicillin-trihydrate were used in the experiments as an active substance at the rate of 800 IU/mg. Ampicillin-sodium was applied in the form of 5 per cent solution, and ampicillin-trihydrate--in the form of a 5 per cent water suspension prepared extempore prior to their administration. Both forms of ampicillin were used once, muscularly, at rates of 0.01 and 0.025 g/kg body weight with calves and sheep. The results of these comparative studies showed that the levels of the serum concentrations of ampicillin and the time of their deposition in both species of animals correlated with the dose, the chemical composition, and the species of animal. The period of retaining the antibiotic in the blood varied in calves and in sheep. Parallel to these studies the excretion of ampicillin from the body was also followed up--in the ewes' milk at muscular administration, rated 0.025 g/kg body weight. It was found that ampicillin-sodium and ampicillin-trihydrate quickly penetrate in the udder, and are observed in the milk at the 30th minute (0.25 microgram--0.38 microgram/cm3).

[Pharmacokinetics of ampicillin in lambs and guinea pigs]. / Niakoi danni ot farmakokinetikata na ampitsilina pri agneta i morski svincheta.

Comparative studies were carried out on the sodium salt of ampicillin and ampicillintrihydrate with the use of guinea pigs and lambs. Ampicillintrihydrate was applied to guinea pigs singly, muscularly and orally, at the rate of 0.025 per kilogram With lambs the two forms of the preparation were used--muscularly at rates of 0.005, 0.01, 0.015, and 0.02/kg; ampicillintrihydrate was tested orally at rates of 0.02, 0.03, and 0.05 kg/weight. For venous application ampicillin-sodium was used at the rate of 0.02/kg under the form of 4 per cent water solution (prepared with distilled water). Data referring to the comparative studies on the two forms of ampicillin--ampicillin-sodium and ampicillintrihydrate--showed that these preparations, after single parenteral and oral administration, are resorbed from the site of application and penetrate into all investigated organs and tissues. Ampicillin developed very soon bacteriostatic concentration in the blood serum in the course of 4-6-8 hours, depending on the amount applied and the route of application.