[Chemotherapy activity and pharmacokinetics of the fluoroquinolones generics Ofloxacin-PhPO and Pefloxacin-genova].

Therapeutic activity, pharmacokinetic and bioavailability on animals (inbred white mouse, rabbits) were evaluated for Ofloxacin-PhPO and Pefloxacin-genova in comparison with innovator products--Tarivid and Abaktal. The results of the experiments demonstrate that investigated generics by their therapeutic efficacy in animals and by bioavailability are similar to original products.

[Relative bioavailability and bioequivalence of the antimycotics ketoconazole and fluconazole].

Pharmacokinetics and bioavailability of the antimycotics ketoconazole FPO and fluconazole (Russia) and the analogous drugs nizoral (Belgium) and diflucan (France) were comparatively studied on animals and in clinical trials. The pharmacokinetic parameters of the drugs were determined and their bioequivalence was shown (90-110%) that is evident of their therapeutic equality.

[Interactions of sulfanilamides, penicillins and acetylsalicylic acid in serum protein binding]. / Vzaimodeistvie sul'fanilamidov, penitsillinov i atsetilsalitsilovoi kisloty pri sviazyvanii ikh syvorotochnymi belkami.

Combined use of sulfalen and sulfadimethoxine with benzylpenicillin and ampicillin resulted in increased binding of sulfalen to serum proteins of man. Acetylsalicylic acid promoted a decrease in the sulfanilamide binding to the serum proteins. The observed changes in the sulfanilamide binding to proteins of human blood serum were due to increased or decreased affinity of the drugs to the protein molecules.

[Rifampicin pharmacokinetics in experimental hepatitis]. / Izuchenie farmakokinetiki rifampitsina pri éksperimental'nom gepatite.

Rifampicin pharmacokinetics in rats with acute affection of the liver with carbon tetrachloride did not alter. Chronic affection with carbon tetrachloride resulted in retarded elimination of the antibiotic from blood. There was observed no relationship between increased activities of transamination enzymes such as alanine aminotransferase and aspartate aminotransferase in blood serum of animals and changes in rifampicin pharmacokinetics.

[Pharmacokinetics of sulfalene and sulfadimethoxine in chronic pyelonephritis patients]. / Farmakokinetika sul'falena i sul'fadimetoksina u bol'nykh khronicheskim pielonefritom.

Accelerated elimination of sulfalen was observed in patients with chronic pyelonephritis, unimpaired glomerular filtration and lowered tubular reabsorption. This was due to lowered sulfalen reabsorption in the kidney tubules. Sulfadimethoxine pharmacokinetics in such patients was not significantly changed.

[Pharmacokinetics of benzylpenicillin and ampicillin in patients after combined administration with sulfalen and sulfadimethoxine]. / Farmakokinetika benzilpenitsillina i ampitsillina u bol'nykh pri kombinirovannom primenenii s sul'falenom i sul'fadimetoksinom.

Combined use of the penicillins and sulfanylamides in patients resulted in increased antibiotic blood levels and circulation. Retarded elimination of the penicillins was mainly due to the depositing effect of the sulfanylamides on the antibiotics at the account of increasing levels of the latter in peripheral tissues which was realized through increasing the drug distribution volume. It is not excluded that the primary mechanism of changing the penicillin kinetics in patients is lowered antibiotic binding to plasma proteins.

[Distribution of sulfanilamides and penicillins in the blood and organs of rats after their combined administration]. / Raspredelenie sul'fanilamidov i penicillinov v krovi i organakh krys pri kombinirovannom primenenii lekarstv.

The use of benzylpenicillin and ampicillin in combination with sulfalen or sulfadimethoxine increased the levels of the penicillins and sulfalen in some organs and tissues of rats. This was accompanied by a rise in the concentration gradients of the drugs. It is concluded that the combined use of the penicillins and sulfanilamides determines their increased penetration from the blood into other organs and tissues of the host.

[Pharmacodynamics of cephaloridine and cephalothin combined with sulfalene in rabbits]. / Farmakokinetika tsefaloridina i tsefalotina u krolikov pri kombinirovannom primenenii s sul'falenom.

The combined use of cephaloridin and cephalothin with sulfalen resulted in decreased binding of the cephalosporins by serum proteins and decreased rate of drug elimination in rabbits. It might be suggested that these two processes were interrelated. The decreased binding of the antibiotics by proteins in rabbits promoted an increase in the volume distribution of the drugs at the expense of a rise in the level of their penetration from the blood into the peripheral tissues.

[Cephalosporin and carbenicillin penetration into the tissues of rats with aseptic inflammation]. / Proniknovenie tsefalosporina i karbenitsillina v tkani krys s asepticheskim vospaleniem.

Two beta-lactam antibiotics with different serum protein binding were studied for penetration into the tissues of rats with aseptic inflammation. It was found that the pharmacokinetics of the drugs in the blood serum differed only in the elimination rate. The levels of the free fraction of cephaloridin were much higher than those of carbenicillin. The maximum concentrations of free cephaloridin in the inflammation exudate, intact and inflamed tissues and the areas under its pharmacokinetic curves were higher than those of carbenicillin. The elimination rate of both the drugs was the same for all the tissues studied.

[Penetration of ampicillin and oxacillin into the tissues of rats with aseptic inflammation]. / Izuchenie proniknoveniia ampitsillina i oksatsillina v tkani krys s asepticheskim vospaleniem.

Penetration of 2 penicillins with different indices of serum protein binding in the tissues of rats with aseptic inflammation was studied. The pharmacokinetics of both penicillins in the blood serum (total preparation) did not differ. However, the level of the ampicillin free fraction was much higher than that of oxacillin. In the inflammation exudate and inflamed tissues, the maximum concentrations of free ampicillin and the area below its pharmacokinetic curve were also higher than those of oxacillin. The rate of elimination of both antibiotics from the exudate was the same. The period of half elimination of the drugs from the exudate and inflamed tissue was significantly higher than the period of their half elimination from the blood serum. High positive correlation between the ampicillin levels in the blood serum and inflamed and intact tissues was shown. As for oxacillin, positive correlation between its levels in the blood serum and inflamed tissue was observed.

[Pharmacokinetics of sulfalene and sulfamethoxine after combined administration with benzylpenicillin and ampicillin]. / Farmakokinetika sul'falena i sul'fadimetoksina pri kombinirovannom primenenii s benzilpenitsillinom i ampitsillinom.

The binding of sulfadimethoxine by serum proteins of rabbits did not change in the presence of benzylpenicillin and ampicillin, while the binding of sulfalen increased. The 1.2-2-fold decrease in the proportion of sulfalen not bound by blood proteins was accompanied by its acetylation in rabbits. This in its turn resulted in a decreased rate of the drug elimination. The penicillins did not change the kinetics of sulfadimethoxine in rabbits. When the dose of sulfadimethoxine was increased 2 times, the rate of its elimination in rabbits increased, which is likely to be due to increased acetylation of the drug. This may be associated with the increased level of the free sulfadimethoxine fraction in the blood because of the drug lower binding by serum proteins. When the dose of sulfalen was increased 2 times, its kinetics in rabbits did not change.

[Effect of acetylsalicylic acid on sulfalene and sulfadimethoxine binding by serum proteins and on their kinetics in rabbits]. / O vliianii atsetilsalitsilovoi kisloty na sviazyvanie sul'falena i sul'fadimetoksina syvorotochnymi belkami i na ikh kinetiku u krolikov.

The use of sulfalen and sulfadimethoxine in combination with acetylsalicylic acid resulted in the decreased binding of the sulfanilamides by serum proteins, most pronounced with respect to sulfadimethoxine. The decreased binding of the drugs by serum proteins in rabbits was accompanied by decreased elimination of sulfalen and increased excretion of sulfadimethoxine from the host. The different effect of acetylsalicylic acid on the kinetics of sulfalen and sulfadimethoxine in the rabbits was partially due to the unequivalent effect of the decreased binding of the sulfanilamides by the serum proteins on their combined use.

[Characteristics of the distribution of long-acting sulfanilamides in purulent pyelonephritis in rats]. / Osobennosti raspredeleniia dlitel'no deistvuiushchikh sul'fanilamidov pri sinegnoinom pielonefrite u krys.

Distribution of sulfalen, sulfadimethoxine and sulfamethoxypyridazine in the blood and organs of rats and binding of the drugs to the blood serum proteins of the animals with experimental P. aeruginosa pyelonephritis were studied. It was shown that in rats with P. aeruginosa pyelonephritis the levels of long-acting sulfanilamides in the blood and organs were lower, while the levels of their penetration through the histohematic barriers were higher, which was partially due to the decreased binding of sulfanilamides to blood proteins.

[Pharmacokinetics of penicillins following combined administration with sulfanilamides]. / Farmakokinetika penitsillinov pri kombinirovannom primenenii s sul'fanilamidami.

Combined use of benzylpenicillin or ampicillin with sulfalen or sulfadimethoxine resulted in a decreased binding of the antibiotics to the blood serum proteins and slower elimination of penicillins from the experimental rabbits. It is quite possible that the decreased levels of the antibiotic binding to the proteins caused their slower elimination rates, which was realized by increasing the volume of the drug distribution mainly at the expense of the peripheral compartment and decreased excretion with the urine.

[Sulfadimethoxine pharmacokinetics in mechanical jaundice and cholangitis]. / Farmakokinetika sul'fadimetoksina u bol'nykh mekhanicheskoi zheltukhoi i kholangitom.

The rate of sulfadimethoxine excretion from blood in patients with mechanical jaundice and cholangitis is the same as that in healthy persons. The renal excretion of the drug in such patients does not undergo any significant changes either. However, excretion of sulfadimethoxine with bile is impaired and the level of suppression of renal excretory function is proportional to the jaundice period. After decompression of the bile ducts renal excretory function in patients with mechanical jaundice is recovered.

[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.

[Sulfadimethoxine pharmacokinetics in chronic nephritis with nephrotic syndrome]. / Farmakokinetika sul'fadimetoksina u bol'nykh khronicheskim nefritom s nefroticheskim sindromom.

Sulfadimethoxine excreted more rapidly in patients with chronic nephritis and the nephrotic syndrome than in subjects of the control group. Increased elimination of sulfadimethoxine from the blood of the persons with the kidney diseases was due to decreased reabsorption of the drug in the kidney tubules and increased rates of the drug biotransformation because of decreased binding by the blood serum proteins.

[Sulfalene circulation in kidney disease patients]. / Tsirkuliatsiia sul'falena u bol'nykh zabolevaniiami pochek.

Examinations of patients suffering from chronic nephritis with the nephrotoxic syndrome and amyloidosis of the kidneys with unchanged glomerular filtration showed that the rate of sulfalen excretion in the patients with the kidney diseases was higher than that in the persons of the control group. The sulfalen elimination rate and the plasmatic clearance in such patients were higher. The higher rate of sulfalen elimination was due to increased excretion of the unchanged drug with urine.