Antibiotiki i meditsinskaia biotekhnologiia = Antibiotics and medical biotechnology最新文献

Experimental studies on rats with sarcoma 45 showed that antitumor efficacy of bleomycetin could be markedly increased by inducing short-term hyperglycemia. It was noted that the theoretical value of the additive effect of these factors was lower than the experimental one. This is in favour of the synergistic mechanism of bleomycetin action under conditions of hyperglycemia.

The modern status of the biological role of peptide antibiotics in vital activity of bacilli is discussed. The published data and the original findings of the author and his coworkers are analyzed from the viewpoint of two hypothesis: regulator and protective. It is shown that at present there is no solid basis for considering antibiotics as positive regulators of sporulation in organisms producing them. Synthesis of antibiotics is thought to be a manifestation of a certain stage in ontogenetic development of bacilli and is associated with production of extracellular enzymes. The enzymes are conjectured to perform in nature hydrolysis of exogenic substrates and thus create nutrient medium for vegetative cell division of antibiotic-producing organisms. The author suggests that the main biological function of peptide antibiotics produced by bacilli is protection of their environment from other microorganisms.

The main stages in studying pharmacokinetics of new drugs are discussed. They include: development of a micromethod for determining drugs in biological objects, estimation of drug stability in biological objects on storage, evaluation of drug distribution coefficients, investigation of drug solubility rate, drug binding to plasma proteins and erythrocytes, studying of drug metabolism in vitro and in vivo, investigation of drug kinetics in test tissues after single and repeated administrations, estimation of drug bioavailability, investigation of drug excretion and distribution in organs and tissues, determination of concentration-effect relationships in test tissues and studying of drug pharmacokinetics in models simulating pathological processes.

Pharmacokinetics and characteristic features of ampicillin kidney distribution were studied in 21 children with chronic pyelonephritis without signs of renal insufficiency who had undergone urological operations. It was found possible to provide the antibiotic concentrations efficient against ampicillin sensitive and partially middle sensitive microorganisms in the renal parenchyma, pelvis wall, ureterocele, megaureter and urinary bladder. Ampicillin concentrations in tissues of the urinary system were shown to correspond to a higher extent to the concentrations attained in blood than those in urine.

Development of rational antibiotic dosing is mainly limited by the absence of a clear conception of the minimum efficient concentration. Studies on antimicrobial effect kinetics in dynamic models in vitro simulating pharmacokinetic profiles observed in humans markedly promote the problem solution. Such an approach enabled one to reveal a relationship between duration or intensity of the antibiotic effect and the area under the concentration/time curve. This relationship depends on the antibiotic pharmacokinetic profile. It is advisable to evaluate antibiotic efficacy against microorganisms by the minimum efficient area under the concentration/time curve and not by the antibiotic minimum efficient concentration. Thus, it is possible to estimate simultaneous contribution of two factors to the antimicrobial effect: drug concentration and exposure time.

Penetration of antibiotics into infected inflammation foci depended on the level of their binding to serum proteins. Low binding ampicillin provided the highest levels of the free antibiotic in both serum and the inflammation foci. At the same time coefficients of antibiotic penetration into purulent infiltrates and infected tissues were close and amounted approximately to 70-80 per cent. Antibiotic elimination from the infection foci was retarded as compared to that from serum.

Studies on ampicillin pharmacokinetics in patients with prostate adenoma showed that adenoma did not influence the antibiotic kinetics. The ampicillin maximum concentration in tissues and organs of the urinary corresponded to the peak concentrations in blood. Therefore, development of dosage regimens providing the drug efficient concentrations in tissues and organs of the urinary tract should be based on ampicillin kinetics in the blood.

Physicochemical characteristics of several aubazidan lots were studied. It was shown that the polysaccharide drug consisted of three fractions. This means that aubazidan is a polydisperse polymer. The polysaccharide structure and properties such as solubility, velocity and optical parameters markedly depended on the cultivation conditions of the organism producing aubazidan. This could be due to different activity of the enzyme responsible for synthesis of the aubazidan molecule.

Pharmacokinetics of eremomycin, a novel original glycopeptide antibiotic was studied. It was shown that after a single intravenous or subcutaneous administration to mice, rabbits and dogs eremomycin concentrations in blood and duration of the antibiotic circulation depended on the dose level and administration route. After subcutaneous or intramuscular administration eremomycin was rapidly absorbed and detected in serum even in 15-30 min. The maximum levels were observed in 2 hours. Absolute bioavailability after subcutaneous administration averaged to 85 per cent. Eremomycin penetrated into organs. The antibiotic concentrations in cerebrospinal fluid were low. The highest concentrations of eremomycin were detected in the kidneys, lungs and spleen. The antibiotic mainly excreted with urine. The renal clearance amounted to 85 per cent of the total clearance. 2-3-month exposure of dogs and rats to eremomycin in doses 4-10 times higher than the approximate single therapeutic doses for humans (250 mg) resulted in cumulation of the antibiotic.

To lower the role of natural antibacterial activity of biological substrates from humans and laboratory animals in microbiological assay of bleomycin (bleomycin) with B. subtilis ATCC 6633 as the test-microbe, it was suggested to increase the procedure sensitivity by using the medium modification. In determining concentrations of aminoglycosides by the agar diffusion method the use of B. pumilus NCTC 8241 as the test-microbe is recommended.