[Flow-type cuvette for photoelectrocolorimeter].
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Biomedical subjects
Publications and source records attributed to I Ia Geĭtman.
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Possible relation between the changes in the penicillin pharmacokinetics and coagulograms under the effect of trypsin in rats and man was analysed. It was found that parenteral administration of the enzyme was accompanied by a simultaneous increase in the penicillin blood level, oliguria, a decrease in the antibiotic amount excreted with urine and drop of the fibrinogen level in plasma. The latter is consequent on intravascular coagulation which results in temporary impairment of the excretion function of the kidneys defining the changes in the penicillin pharmacokinetics under the effect of trypsin.
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The effect of penicillin, tetracycline, aminoglucozide antibiotics and streptomycin on BAEE-esterase activity of trypsin was studied. It was found that benzylpenicillin in amounts of 50, 100 and 300 mg, ampicillin in an amount of 25 mg, methicillin in an amount of 12 mg and tetracycline in an amount of 2.5 mg as calculated per 1 mg of trypsin had no effect in vitro on the esterase activity of the enzyme. Neomycin, kanamycin and streptomycin in amounts of 5, 10, 100 or 300 mg per 1 mg of trypsin catalyzed splitting of BAEE by trypsin. When the antibiotics were added to the bile, its esterase activity increased. Preliminary intramuscular administration of trypsin and kanamycin to the rats had no effect on the ampicillin levels in the blood serum and brain and did not affect the permeability of the hemato-encephalic barrier as compared to the use of trypsin alone.
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The effect of cymotrypsin on excretion of penicillin, methicillin, oxacillin, streptomycin and gentamycin with urine including the kidney clearance was studied on rabbits. It was found that the enzyme introduced intramuscularly in a dose of 20 mg/kg increased excretion of penicillin, methicillin, oxacillin and gentamycin by 37, 24, 26 and 16 per cent respectively. The only exclusion was streptomycin. Chymotrypsin increased the kidney clearance of penicillin, methicillin, oxacillin, streptomycin and gentamycin by 1.7, 1.9, 2.2, 1.2 and 1.5 times respectively.
The effect of trypsin or chemotrypsin on the levels of benzylpenicillin, ampicillin, oxacillin, kanamycin or tetracycline in the peritoneal inflammation fluid, as well as the effect of trypsin on penetration of these antibiotics into the granulemas of 2 types was studied. It was found that intramuscular administration of the enzymes to animals in a dose of 10 mg/kg resulted in increased levels of penicillins and kanamycin in the inflammation peritoneal fluid. An analogous effect of trypsin was observed with respect to experimental granulemas. The levels of tetracycline in restricted inflammatory foci increased only after intraperitoneal administration of trypsin to rats. Increased penetration of benzylpenicillin into the peritoneal fluid and connective tissue granulema under the effect of the enzymes was observed. The effect of trypsin on penetration of benzylpenicillin into granulema according to Selie did not differ from the effect of the enzyme on penetration of semisynthetic penicillins and kanamycin into it.
The effect of chemotripsin on the pharmacokinetics of ampicillin as dependent on the drug dose and the administration intervals was studied on rats using the method of the experiment design. With the use of the method it was found that intramuscular injections of chemotripsin to rats in doses of 3, 4.5, 6, 8 and 10 mg/kg, 0.5, 1, 1.5 and 2 hours before intramuscular administration of ampicillin in doses of 10, 20, 35, 75 and 100 mg/kg caused a simple effect inducing an increase in the antibiotic levels in the blood and organs, when the enzyme and antibiotic were present simultaneously in the animal organism for an hour. The increase in the antibiotic levels in the rat organs due to simultaneous presence of chemotripsin and ampicillin the animal organism for 2 hours was less pronounced
The effect of intramuscular chimotripsin on the levels of methicillin and tetracycline administered respectively intramuscularly and orally was studied in patients with chronic pneumonia and in experimental rats. It was found that the dose of chimotripsin providing higher methicillin blood levels was many times lower than the enzyme doses providing analogous indices for the blood serum and organs of the rats. When the patients were treated with tetracycline and chimotripsin, increased blood levels of the antibiotic were observed. Administration of chimotripsin to the rats had no effect on tetracycline pharmacokinetics in the animals.
Trypsin and chemotrypsin administered intramuscularly to rats in doses of 2 and 10 mg/kg respectively prior to benzylpenicillin, ampicillin or oxacillin administered also intramuscularly were studied with respect to their effect on the pharmacokinetics of the antibiotics. The latter 2 antibiotics were additionally studied after their oral administration. It was found that trypsin and chemotrypsin had almost the same effect on the pharmacokinetics of the penicillins in the animals, when administered intramuscularly and the effect did not depend on the doses of trypsin and chemotrypsin (2 and 10 mg/kg). No significant differences in the effect of the enzymes on the pharmacokinetics of ampicillin and oxacillin administered orally was registered. Combination of prior injection of every of the enzymes followed by oral administration of the semisynthetic penicillins resulted in a more pronounced increase in the levels of the antibiotics in the blood serum and organs of the rats as compared to that after intramuscular administration of the antibiotics.
The effect of chimotripsin on the level and duration of the ampicillin concentration increase in rats, as well as the effect of the enzyme on the in vitro antibiotic detection in the blood serum and organ homogenates of the animals was studied. It was found that rational combined use of ampicillin and chimotripsin required the enzyme administration not later than 1 hour before the antibiotic injection. Chimotripsin provided increased ampicillin levels in the blood serum and liver of the rats for at least 5 hours and in the kidneys and lungs for at least 4 hours. The enzyme present in the rats for 2 hours had no effect on determination of ampicillin activity in vitro in the presence of the blood serum and organ homogenates of the animals.