[Microflora study and the pharmacokinetic characteristics of gentamycin in children with mucoviscidosis]. / Izuchenie mikroflory i osobennostei farmakokinetiki gentamitsina u detei, bol'nykh mukovistsidozom.

P. aeruginosa and Staphylococcus were isolated respectively from 46.7 and 30.9 per cent of the children with mucoviscidosis. Proteus, Klebsiella and hemophilic bacilli were isolated from 11.2, 2.8 and 2.8 per cent of the patients respectively. All the isolates of Proteus, 95.8 per sent of the staphylococcal strains and 16.7 per cent of the P. aeruginosa strains were highly sensitive to gentamicin. No gentamicin resistant strains were detected. The studies on the gentamicin pharmacokinetics showed that the maximum levels of the drug in the blood and sputum of the children treated with the antibiotic injected intramuscularly in doses of 1.2 and 2-2.5 mg/kg were attained in 1 hour. The concentration of gentamicin in the sputum amounted to 60-80 per cent of its concentration in the blood serum. Within 11 hours the antibiotic sputum levels were higher than the MIC for the organisms sensitive to gentamicin. After a single endobronchial administration of the drug it was detected in the sputum for 6 days in concentrations exceeding the MIC for the moderately sensitive strains.

[Pharmacokinetics of cefamandole in rabbits]. / Farmakokinetika tsefamandola v organizme krolikov.

The pharmacokinetics of cephamandol administered intramuscularly in single doses of 5 or 20 mg/kg and intravenously in a single dose of 5 mg/kg was studied on rabbits. When the antibiotic was administered intramuscularly, a one-compartment model was used for determination of the parameters of the antibiotic pharmacokinetics in the blood serum, while on intravenous administration of the antibiotic a two-compartment model was used. It was found that the rate of cephamandol elimination after intramuscular administration did not depend on the drug dose. The antibiotic half-life was 34-37 minutes. The apparent volume of the antibiotic distribution after intramuscular administration was 0.31-0.71 ml/g. After intravenous injection of cephamandol the apparent volume of its distribution in the central compartment was 0.27 ml/g. The stationary and kinetic volumes of the antibiotic distribution were 0.36 and 0.46 ml/g, respectively. The average values of the antibiotic elimination constant, the constant of the antibiotic passage from the central compartment to the peripheral one and vice versa were 0.0446, 0.0193 and 0.0546 min-1, respectively. After intravenous injection the rate of cephamandol elimination from the rabbit blood was higher: the antibiotic half-life after intravenous injection was 26.1 min.

[Cephalosporin pharmacokinetics in rabbits]. / Farmakokinetika tsefalosporinov v organizme krolikov.

The kinetics of the blood serum and urine levels of cephalotin, cephaloridine, cephazolin, cephacetrile, cephapirin, cefalexin and cefradin was studied on rabbits treated with the antibiotics administered intravenously. The pharmacokinetic constants of the cephalosporins were calculated on the basis of the one-compartmental mathematical model. It was shown that cephalotin and cephapirin had the highest blood elimination rates. These antibiotics had higher constants of the elimination rate and lower time values of a two-fold decrease in the blood level. The elimination rates of the other cephalosporins were almost the same. The drugs did not differ in renal clearance. Cephapirin, cephalotin and cephacetrile had the lowest values of excretion with the urine. It was found that the tubular secretion took part in the renal excretion of all cephalosporins. Its proportion was especially high in renal excretion of cephalotin, cephapirin, cephazolin. The value of the "apparent" distribution was much higher for cephalotin, cephacetrile, cefradin and cephapirin as compared to the other drugs. The highest values of the total clearance were observed with respect to cephalotin, cephacetrile and cephapirin, as well as higher values of the extrarenal clearance.

[Pharmacokinetic interference between furosemide and cephalosporins]. / K voprosu o farmakokineticheskoi interferentsii mezhdu furosemidom i tsefalosporinami.

The effect of furosemid was studied on rats in comparison to that of etamid with respect to circulation in the body of some cephalosporins, such as cephalotin, cephaloridin, cephazolin, cephacetrile, cephapirin, cefradin and cefalexin. Furosemid and etamid were administered to the rats intraperitoneally in a dose of 100 mg/kg 30 minutes before exposure to the cephalosporins. Cefalexin was administered intragastrically in a dose of 100 mg/kg and the other cephalosporins were administered intramuscularly in a dose of 20 mg/kg. It was found that furosemid increased the blood levels of all cephalosporins in the rats and especially those of cephaloridine and cephacetrile, the levels being increased 5-6 times. The effect of etamid was analogous but less pronounced. Furosemid significantly decreased the renal excretion of some cephalosporins, i.e. cephaloridine, cephalotin, cephacetrile and cephazolin and had an insignificant effect on renal excretion of the other antibiotics. Etamid did not inhibit renal excretion of the cephalosporins.

[Comparative study of the interaction of cephalosporins with blood serum proteins and organ homogenates]. / Sravnitel'noe izuchenie vzaimodeistviia tsefalosporinov s belkami syvorotki krovi i gomogenatami organov.

Interaction of 7 semisynthetic antibiotics (cephaloridine, cephalexin, cephradine, cephazolin, cephalotin, cephacetrile and cephapirin) with proteins of human, bovine and rabbit blood serum, as well as organ and tissue homogenates of rats was studied comparatively. The study showed that binding of the cephalosporins by the blood serum depended on both the chemical structure of the antibiotic and the species affiliation of the protein substrate. The binding lvels of cephazolin and cephalotin by the blood serum proteins (except bovine serum) were the highest, while the binding level of cephaloridine was the lowest. A significant decrease in the values of binding by the serum proteins of the drugs with high percentage of binding was observed when the drug concentrations in solution were increased. Binding of the cephalosporins by the blood serum proteins was in most cases completely reversible. The activity of the cephalosporins decreased in the presence of the rat organ and tissue homogenates. The levels of the activity decrease as compared to the theoretical ones were the highest with the use of cephalotin, cephacetrile and cephapirin. The lowest values of detection of these antibiotics were noted on their incubation with the liver, kidneys and lungs.

[Comparative study of cephalexin and cephradine distribution in the body of rats]. / Sravnitel'noe izuchenie raspredeleniia tsefaleksina i tsefradina v organizme krys.

Distribution regularities of cephalexin and cephradine, 2 semisynthetic cephalospor in antibiotics for oral use were studied on rats. It was found that the cephalosporins had a capacity for satisfactory penetration through the histochematological barriers. The drugs were rather rapidly absorbed from the gastrointestinal tract of the rats into the blood. Their maximum blood levels were determined 1 hour after the administration. The highest cephalosporin concentrations were detected in the kidneys and liver. Still, the level of cephradine in the kidneys was lower and that in the liver was higher than the levels of cephalexin. The lowest concentrations were found in the skeletal muscles. The character of cephradine distribution in the lungs, heart and spleen differed from that of cephalexin; the maximum concentrations of cephradine in these organs were achieved 1 hour after its administration, while those of cephalexin were achieved in 30 minutes. The antibiotics were not detected in the brain tissue. No increase in the concentration gradient with time was observed.

[Comparative study of the distribution of semisynthetic cephalosporins in the body of rats]. / Sravnitel'noe izuchenie raspredeleniia polusinteticheskikh tsefalosporinov v organizme krys.

Distribution of 6 cephalosporin antibiotics, i. e. cephaloridin, cephalotin, cephradin cephacetryl, cephazolin and cephapyrin for parenteral use was studied comparatively on rats. The studies showed that all the above cephalosporins were well absorbed into the blood after intramuscular administration. The highest serum levels were achieved with the use of cephozolin. Still, its levels in the animal organs were mainly not higher and sometimes even lower than those provided by the other antibiotics. The highest levels of cephalosporins were detected in the kidneys. Cephalotin, cephapyrin and cephacetryl differed by the character of their distribution in the rats from the other 3 antibiotics: the levels of cephalotin and cephapyrin in the heart, spleen and muscles were lower than those of the other cephalosporins; sometimes they were even not detected in these organs; cephacetryl was not found in these organs. The levels of these 3 antibiotics in the kidneys were lower than those of the other cephalosporins. Cephalotin, cephacetryl and sometimes cephapyrin were not detected in the rat liver. None of the cephalosporins was found in the brain tissue.

[Cephazolin and cephapirin circulation in the blood of rabbits]. / Tsirkuliatsiia tsefazolina i tsefapirina v krovi u krolikov.

Circulation of 2 semi-synthetic cephalosporins, i. e. cephazoline and cephapyrine in the blood of rabbits after their intramuscular administration in single doses of 5 and 20 mg/kg was studied. It was found that the antibiotics were well adsorbed into the blood. Their maximum blood levels were achieved 15--30 minutes after administration. Cephazoline provided a higher blood level persisting for longer periods of time as compared to cephapyrine. The value of the time of the two-fold decrease in the cephazoline blood level was higher. A four-fold increase in the dose of the cephalosporines resulted in an increase in their blood levels but did not induce any significant increase in the time of their circulation.

[Pharmacokinetics of semisynthetic cephalosporins for parenteral use on surgical patients]. / Farmakokinetika polusinteticheskikh tsefalosporinov dlia parenteral'nogo primeneniia u khirurgicheskikh bol'nykh.

Pharmacokinetics of 4 cephalosporanic antibiotics for parenteral use, i. e. cephaloridine, cephradine, cephazoline and cephacetryl was studied in surgical patients with normal function of the kidneys and liver. The first 3 drugs were well absorbed after intramuscular administration, their maximum serum levels being achieved during the first hour. High blood levels of cephacetryl were determined after its intravenous administration. When cephaloridine, cephradine and cephazoline were administered in equal doses, it was found that the first 2 drugs did not practically differ with respect to the values of the serum levels, the rate of elimination from the blood, the rate and level of excretion with the urine. Cephazoline was characterized by higher blood levels and slower elimination from the blood.

[Pharmacokinetics of cephalexin and cephradine in surgical patients]. / Farmakokinetika tsefaleksina i tsefradina u khirurgicheskikh biol'nykh.

Pharmacokinetics of 2 oral cephalosporin antibiotics, i.e. cephalexin and cephradin in surgical patients with normal function of the liver and kidneys was studied. Both the drugs were satisfactorily absorbed into the blood reaching the maximum level in 1 hour. The antibiotics were determined in close concentrations in the blood serum of the patients during 5 hours of the observation. No differences in the time of a two-fold decrease in the antibiotic serum level and the value of the area limited by the antibiotic blood level were found. Cephalexin and cephradin were excreted with the urine in equal amounts.