[Sisomicin pharmacokinetics in rat tissues in single and long-term administration]. / Farmakokinetika sizomitsina v tkaniakh krys pri odnokratnom i dlitel'nom vvedenii preparata.

The pharmacokinetics of sisomicin administered intramuscularly to rats in daily doses of 12.5 and 25 mg/kg for 30 days was studied. After a single administration of the drug in the above doses the highest and the lowest levels of sisomicin were observed in the kidney cortical layer and liver, respectively. The antibiotic level in the tissues rose with an increase in the antibiotic dose and duration of the drug use. The two-fold rise in the dose resulted in an elevation in the sisomicin level in the kidney cortical layer by 1.7 times, in the medullary layer by 3 times, and in the blood serum, lungs and spleen by 2.3, 1.2 and 1.5 times, respectively. After treatment with a dose of 25 mg/kg for 8 days the antibiotic level in all tissues studied was higher than that after the first administration of the drug: in the cortical and medullary layers of the kidneys by 5-7 times and in the blood serum and other tissues by 1.2-2 times. When sisomicin was used repeatedly in any dose, stabilization of or some decrease in the mean integral concentration of the antibiotic in the kidney cortical layer and a continuous increase of this value with respect to the medullary layer (up to the 30th day) were noted. The difference between the antibiotic levels in the kidney layers after the repeated administration of the drug was less pronounced than that after a single administration of the drug. The cumulation index of sisomicin in the kidney cortical layer persisted at the same level and that in the medullary layer gradually increased. In this connection it is concluded that correlation between the sisomicin nephrotoxic effect and the level of the antibiotic in the kidney cortical layer is more pronounced than that in the medullary layer.

[Rapid microbiological method of determining the gentamicin, sisomicin and kanamycin concentrations in patients' serum]. / Uskorennyi mikrobiologicheskii metod opredeleniia kontsetratsii gentamitsina, sizomitsina i kanamitsina v syvorotke krovi bol'nykh.

A modification of the microbiological agar-diffusion method for rapid determination of gentamicin, sisomycin and kanamycin levels in the blood serum of patients is described. The decrease in the time for determination of the antibiotic levels in the serum specimens with the modified method was provided by the use of a higher inoculation dose of the test microbe, higher levels of the incubation temperature and an enriched nutrient medium. The assay time was decreased from 18 to 3--4 hours as compared to the routine agar-diffusion method.

[Cephalexin pharmacokinetics]. / Farmakokinetika tsefaleksina.

The pharmacokinetics of cephalexin monohydrate after its oral administration in a single dose was studied on rats and dogs. The analysis of the pharmacokinetic data obtained with the one-compartmental model showed that the rate of the antibiotic absorption in the rats was higher than that in the dogs. The periods of the cephalexin half-absorption and maximum concentration were 0.2 and 1.1 hour in the rats and 0.64 and 1.9 hours in the dogs respectively. The period of the antibiotic half-life was almost the same in both animal species. Selective localization of cephalexin in the kidney and liver tissues was noted. The antibiotic was mainly excreted by the kidneys (98.8 per cent for 24 hours).

[Prolonged-action gentamycin sulfate eyedrops]. / Glaznye kapli gentamitsina sul'fata prolongirovannogo deistviia.

A new dosage form of gentamicin, 0.3 per cent eye drops with polyglucin was developed. Its pharmacokinetics and chemotherapeutic properties were studied. It was shown that in the form of eye drops gentamicin has a prolonged action, provides high levels of penetration into the eye tissues and is effective in the treatment of eye infections.

[Clinical study of sodium dicloxacillin for intravenous administration in heart surgery patients]. / Klinicheskoe izuchenie diklosatsillina natrievoi soli dlia vnutrivennogo vvedeniia u kardiokhirurgicheskikh bol'nykh.

Sodium dicloxacillin for intravenous administration manufactured in the USSR was studied clinically in 21 cardiosurgical patients. The patients were operated with the use of artificial circulation. 16 patients received the drug for counteracting purulent inflammatory complications during the postoperative period. 5 septic patients were treated with dicloxacillin with curative purposes. The antibiotic proved to be highly effective in treatment and prevention of postoperative purulent complications in patients subjected to open-heart operations. 80 per cent of the Gram-stained isolates were sensitive to dicloxacillin. No pronounced complications with respect to the liver were observed in the patients treated with dicloxacillin.

[Pharmacokinetic validation of the nephrotoxic action of sisomycin. The relationship between nephrotoxicity and sisomycin concentration in the blood serum of rats]. / Farmakokineticheskoe obosnovanie nefrotoksicheskogo deistviia sizomitsina. Sviaz' mezhdu nefrotoksichnost'iu i kontsentratsiei sizomitsina v syvorotke krovi krys.

The kinetics of urine nitrogen in the blood serum and morphological changes in the kidneys after a single and repeated intramuscular administrations of the antibiotic in doses of 12.5 and 25 mg/kg a day were studied in Wistar rats. When sisomycin was administered in a dose of 12.5 mg/kg, the increase in the urine nitrogen level after 1--30 injections was reversible, whereas at a dose of 25 mg/kg it became irreversible already after the 5th injection. Maximum deviations in the urine nitrogen level observed within 3--6 hours after each injection of sisomicin were recorded after the 5th injection of the drug in a dose of 12.5 mg/kg and even after the 1st injection of the drug in a dose of 25 mg/kg. The deviations increased up to the 5th and 16th injection of sisomycin in doses of 12.5 and 25 mg/kg respectively. Later the deviations were less pronounced. Regardless of the dose, adipose degeneration in renal tubules was registered after 8--16 injections of the drug. By the 30th and 16th days of the drug administration in doses of 12.5 and 25 mg/kg respectively, the above changes also decreased. On the whole, pronounced functional and morphological changes in the kidneys correlated with the antibiotic dose. Relationship between the time from the beginning of sisomycin administration and the moment when the average integral concentration of the urine nitrogen increased to the upper limit of normal and the logarithm of the average integral concentration of the antibiotic in the serum was found. The safety of the clinical schemes for the use of sisomicin was estimated with the help of this relationship with respect to its nephrotoxic effect.

[Pharmacokinetic basis of the nephrotoxic action of sisomycin. The pharmacokinetics of sisomycin in single and multiple administrations to rats]. / Farmakokineticheskoe obosnovanie nefrotoksicheskogo deistviia sizomitsina. Farmakokinetika sizomitsina pri ego odnokratnom i mnogokratnom vvedenii krysam.

The pharmacokinetics of sisomicin was studied on Wistar rats. The antibiotic was used in single or repeated doses of 12.5 and 25 mg/kg. The kinetic data of the antibiotic titration in blood serum within 1 and 24 hours of intramuscular administration of the drug were formalized with the use of a linear two-compartment model. The average values of the elimination constant and the constants of sisomycin transfer from the central compartment into the peripheral one were 0.64, 0.34 and 0.13 hours-1 respectively. The value of the apparent distribution volume in the central compartment was 0.38 ml/kg and that of the stationary and kinetic distribution volumes was 1.37 and 3.06 1/kg respectively. The value of the general clearance was 0.24 1/(kg.hour) and that of the sisomicin half-life was 8.7 hours. Comparison of the antibiotic levels estimated with a model and actually measured in the blood after repeated administrations revealed the drug cumulation. When the antibiotic was used in a dose of 25 mg/kg daily, its cumulation was observed earlier (by the 5th--8th day) than on its use in a dose of 12.5 mg/kg (by the 30th day). Irrespective of the dose, sisomicin cumulation was accompanied by prolongation of the antibiotic half-life in the rats.

[Doxycycline bioavailability in capsules]. / Biodostupnost' doksitsiklina v kapsulakh.

Soviet doxycycline capsules in a dose of 0.1 g were studied in vitro (for disintegration and solubility) and in vivo (pharmacokinetics on 25 patients). It was found that Soviet doxycycline capsules provided comparatively rapid absorption of doxycycline. The antibiotic availability may be characterized by the solubility test. The results of the study on bioavailability of Soviet doxycycline capsules were compared with the results of analogous studies published by American authors for doxycycline capsules manufactured by various firms of the USA.

[Clinical study of oxacillin for intravenous administration in heart surgery after operations with artificial circulation]. / Klinicheskoe izuchenie oksatsillina dlia vnutrivennogo vvedeniia v kardiokhirurgii posle operatsii s iskusstvennym krovoobrashcheniem.

Intravenous sodium oxacillin of Soviet production was subjected to clinical trials in 50 cardiosurgical patients. The patients were operated under conditions of artificial circulation. The antibiotic was used for prophylaxis and therapy of the postoperative pyo-inflammatory complications. In the group of the patients observed no lethal cases due to the post-operative infection were registered.

[Effect of proteolytic enzymes on kanamycin pharmacokinetics in experimental suppurative infection]. / Vliianie proteoliticheskikh fermentov na farmakokinetiku kanamitsina v usloviiakh éksperimental'noi gnoinoi infektsii.

The effect of the proteolytic enzyme trypsin on kanamycin pharmacokinetics in rats with experimental purulent infection was studied. An increase in the kanamycin serum levels after administration of the drugs in combination was observed as compared to the control. In a dose of 0.03 mg per animal trypsin had no effect on the kanamycin pharmacokinetics in the rats with experimental peritonitis.

[Use of a semisynthetic broad-spectrum penicillin (ampicillin) in surgical practice]. / Primenenie polusinteticheskogo penitisillina shirokogo spektra deistviia (ampitsillina) v khirurgicheskoi praktitke.

Parenterally ampicillin was used for the treatment of 87 patients with lung and abdominal diseases, liver abscesses, extremity phlegmonas, osteomyelitis and other diseases. The antibiotic was administered intravenously and intramuscularly. High efficacy of the treatment was observed in all the cases with ampicillin sensitive microflora. In some cases a satisfactory therapeutic effect was observed only with the use of ampicillin in combination with other antibiotics and aminoglycosides in particular. No side effects of the antibiotic were registered.

[Optimal regime of intravenous administration of lincomycin in osteomyelitis]. / Optimal'nyi rezhim vnutrivennogo vvedeniia linkomitsina pri osteomielite.

The pharmacokinetics of lincomycin in the blood of 8 patients with osteomyelitis was studied on the drug single and uninterrupted intravenous administration in therapeutic doses. It was found that when the antibiotic was administered continuously according to the routine scheme, its therapeutic blood levels were attained only 1.5 hours after the drug infusion. The optimal regimen of lincomycin uninterrupted infusion providing its constant rate in combination with the single intravenous administration was estimated with the help of the constants of the two-compartment model of lincomycin pharmacokinetics. According to the calculations the rate of the antibiotic administration necessary for providing therapeutic levels should be 2.2 mg/kg in complex with the loading dose equal to 5.4 mg/kg. Practical trials showed that intravenous administration of lincomycin with the above regimen remained within therapeutic range already 10 to 20 minutes after the beginning of the drug infusion. Therefore, from the pharmacokinetic point of view the recommended regimen for lincomycin infusion should be considered preferable to that used presently.

[Pharmacokinetics of lincomycin in experimental animals]. / Farmakokinetika linkomitsina u eksperimental'nykh zhivotnykh

When administered parentally, lincomycin satisfactorily penetrated into the organs and tissues of experimental animals. Pronounced tropism of the antibiotic in the bone tissue was observed which provided its recommendation for the treatment of osteomyelitis. The antibiotic was excreted with urine and bile.

[Pharmacokinetics and enzymatic transformations of 35S-lincomycin in the tissues of certain organs]. / Farmakokinetika i fermentativnye prevrashcheniia 35S-linkomitsina v tkaniakh nekotorykh organov

Pharmacokinetics of 35S-lincomycin was studied with the microbiological and radiometric methods of the antibiotic determination. Significant deviations in the results obtained with the two methods in determination of lincomycin levels in the liver and kidneys were observed. The values obtained with the radiometric method were 10 times higher than those obtained with the microbiological method. Paper radiochromatography of the extracts from the liver and kidneys of the animals treated with 35S-lincomycin revealed the presence of not only 35S-lincomycin, but also a number of the label containing substances, the products of the antibiotic enzymatic transformation. Radiochromatography of the extracts from the brain of the animals treated with 35S-lincomycin revealed several peaks of radioactivity against the back ground of low levels of the label.

[Rate of tetracycline dissolution from tablets and capsules and the biological availability of the antibiotic]. / Skorost' rastvorennia tetratsiklina iz tabletok i kapsul i biologicheskaia dostupnost; antibiotika

Relation between the rate of tetracycline dissolution from tablets and capsules and the biological acceptibility of the antibiotic in the host was studied. The antibiotic dissolution rate from the pharmaceutical forms was determined in a modernized apparatus "Rotary basket" in water, the speed of the basket rotation was 200 r.p.m. In addition the tetracycline blood levels in patients treated with the drug in the above pharmaceutical forms were estimated. It was found that the rate of the antibiotic dissolution characterized the antibiotic biological acceptibility. A test for the dissolution rate was developed. It may be used for estimation of production batches of tetracycline tablets.