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A A Firsov

Publications and source records attributed to A A Firsov.

At least 73 records · Page 4Linked to original sources
PubMed1987

[Dependence of the antimicrobial effect on the antibiotic concentration in modelling pharmacokinetic profiles in vitro: a comparison of 2 regimens for the single intravenous administration of sisomicin].

Kinetics of sisomicin antimicrobial effect on E. coli was studied in an in vitro dynamic model. Pharmacokinetic profiles observed in blood of humans treated with different polar dosing schedules i. e. bolus administration and continuous infusion were simulated. The first set of the experiments included simulating the profiles observed at short-term maintenance (0.25-20 min) of relatively high antibiotic levels after bolus administration (Cmax = 0.125-10 micrograms/ml). The second set included simulating the profiles observed at long-term maintenance (1-15 hours) of relatively low antibiotic levels after infusion (Cmax = 0.125-1.75 micrograms/ml). Changes in the viable count in the dynamic model were estimated microcolorimetrically with BioActivity Monitor LKB 2277-202. The use of the recently developed parameters of antimicrobial effect intensity IE and duration TE provided determination of relationship between IE or TE and logarithm of the area under the concentration-time curve (lg AUC). Its own IE (or TE) vs lg AUC curve including 4 phases corresponded to every administration schedule i. e. bolus and infusion. The 1st and 3rd phases reflected weak changes in IE or TE at significant increasing of the AUC and the 2nd and 4th phases reflected a marked increase in IE or TE at insignificant changing of the AUC.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriological Techniques↗
PubMed1987

[Pharmacokinetic study of aclarubicin. The pharmacokinetics of the preparation and its biologically active metabolites in the blood of rats].

Blood pharmacokinetics of the antitumor antibiotic aclarubicin and its metabolites was studied in rats with high performance liquid chromatography. The drug was administered intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. Aclarubicin pharmacokinetics was shown to be nonlinear. However, within every dose level it obeyed a two-compartment model. The nonlinearity could be due to saturation of aclarubicin binding to blood plasma proteins. The blood concentrations of metabolites MA144 N1 and MA144 T1 were close and after 12-18 hours exceeded those of unchanged aclarubicin. The half-lives of aclarubicin and its metabolites ranged from 16 to 21 hours. The MA144 T1 content was not significant. Following oral administration aclarubicin was rapidly absorbed and its bioavailability amounted to 35 per cent. Total bioavailability of aclarubicin, MA144 N1 and MA144 T1 was equal to 89 per cent. This enabled to consider the oral route of aclarubicin administration promising in tumor therapy.

Aclarubicin↗
PubMed1987

[Pharmacokinetic study of aclarubicin. The distribution of the preparation and its biologically active metabolites in rat tissues].

Tissue pharmacokinetics of aclarubicin and its active metabolites was studied with high performance liquid chromatography. The drug was administered to rats intravenously in single doses of 5 and 10 mg/kg and orally in a single dose of 10 mg/kg. With both the administration routes the highest concentrations of the drug and its metabolites were attained in the lymph nodes. Then followed the spleen and lungs. The lowest content of the drug was detected in the heart. The total values of the areas under the concentration/time curves for aclarubicin and its metabolites in the tissues of the heart, lungs, lymph nodes and spleen after oral administration were respectively 2, 3, 4 and 7 times lower than those after the drug intravenous administration in the same dose. The concentrations of the active metabolites MA144N1 and MA144T1 exceeded those of aclarubicin and were detected in the tissues within a longer period as compared to the unchanged drug. With repeated administration preferential accumulation of the metabolites in the tissues and their increased contribution to the aclarubicin antitumor effect could be suspected.

Aclarubicin↗
PubMed1987

[Pharmacokinetics of rifampicin administered intravenously to pulmonary tuberculosis patients].

Pharmacokinetics of rifampicin studied in 15 patients after its intravenous administration in a dose of 10 mg/kg was described by a two-compartment model. The drug levels in serum and urine were determined with a chemical method. At the moment of the infusion discontinuation the maximum drug levels in serum averaged to 14.05 micrograms/ml. The mean values of the total clearance, distribution of the kinetic volume and half-lives were 93.2 ml/(h X kg), 1016.1 ml/kg and 8.1 h respectively. Cumulative excretion of the total rifampicin within 24 hours amounted to 19.4 per cent of the administered dose, the proportions of the main metabolite (25-O-desacetyl rifampicin) and intact rifampicin being equal to 29 and 71 per cent respectively. The renal and nonrenal clearance of rifampicin amounted to 14.2 and 79 ml/(h X kg) respectively.

Adult↗
PubMed1987

[The main trends in the area of the pharmacokinetic study of chemotherapeutic agents].

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.

Anti-Bacterial Agents↗
PubMed1986

[Pharmacokinetics of amikacin in the perilymph and blood serum. An approach to the comparative evaluation of the potential ototoxicity of aminoglycoside antibiotics].

The pharmacokinetics of amikacin in serum and perilymph was studied on guinea pigs treated with its single subcutaneous administrations in doses of 100, 200, 400 and 800 mg/kg. Proportional relation between the values of the areas under the concentration against time curves of the antibiotic in serum and perilymph was shown. It suggested that the level of the antibiotic penetration into the internal ear might be predicted by the area under the concentration against time curve of the aminoglycoside. It was demonstrated that in equitherapeutic doses when D/Deq = 1 aminoglycosides had different areas under the concentration against time curve. Thus, the area under the curve of amikacin was 2.2 times higher than that of sisomicin. It was also demonstrated that the angle coefficient characterizing the relationship between the area under the concentration against time curve in perilymph and the dose standardized with respect to the equitherapeutic value was markedly higher for amikacin than for sisomicin.

Amikacin↗
PubMed1986

[Modelling of rifampicin pharmacokinetics in experimental animals administered the drug intravenously and internally].

Pharmacokinetics of rifampicin on its single intravenous and oral administration to rats in doses of 25 and 50 mg/kg and on its intravenous administration to dogs in doses of 8 and 25 mg/kg was studied. When the antibiotic was administered intravenously to the animals, its pharmacokinetics was nonlinear. The linearity distortion in the rats was lower than in the dogs. However, the pharmacokinetic data relevant to the antibiotic administration in the above doses were satisfactorily described by the biexponential equation. The absolute extent of rifampicin systemic absorption following oral administration to the rats was 60 to 85 per cent. Tissue availability of the antibiotic on its intravenous administration was lower than that on its oral administration.

Absorption↗
PubMed1986

[Interrelations in the changes in the pharmacokinetics and nephrotoxic effect of sisomycin as affected by cefazolin].

The action of cefazolin on the pharmacokinetics and nephrotoxic effect of sisomicin was studied on Wistar rats. Sisomicin in doses of 12.5 and 25 mg/kg alone or in combination with cefazolin in doses of 90 and 360 mg/kg was administered intramuscularly to the animals daily for 16 days. It was shown that in both the doses cefazolin had no noticeable action on the level of the functional and morphological changes in the kidneys. Consequently, there were no significant changes in the levels of sisomicin in serum and the site of the nephrotoxic effect (cortical layer of the kidneys) and in the half-life of the aminoglycoside in the kidney cortical layer under the action of cefazolin. At the same time there was observed a marked individual variability of the levels of urea nitrogen and sisomicin in serum of the rats treated with the aminoglycoside alone or in combination with cefazolin. Analysis of the dependence of the nephrotoxic effect on concentration of sisomicin in serum after its use alone or in combination with cefazolin revealed that the changes in the individual intensity of the effect in all the cases were mainly induced by the changes in the sisomicin blood levels. Therefore, control of the blood levels of the aminoglycoside should provide prevention of the development of its nephrotoxic effect not only in monotherapy but also in the use of aminoglycosides in combination with cefazolin.

Animals↗
PubMed1986

[Pharmacokinetics of cefazolin during hemosorption and hemodialysis].

The influence of hemosorption and hemodialysis on the pharmacokinetics of cefazolin was studied in 20 patients with chronic and acute renal insufficiency. The integral mean value of the antibiotic extraction coefficient in hemosorption was approximately 2 times higher than that in hemodialysis. In the first case the value of this parameter systematically lowered with time (the constant of the process rate amounted to 0.89 h-1), while in the second case it was constant.

Cefazolin↗
PubMed1985

[A dynamic system for the in vitro study of the kinetics of the antimicrobial effect of antibiotics in pharmacokinetic changes in their concentration].

The present approaches to in vitro investigation of the kinetics of the antibiotic antimicrobial effect are based on its recording at one or another constant concentration of the drugs. The regularities revealed under such conditions do not usually reflect the peculiar effect of the drugs in vivo, since with the use of the routine schemes of dosing the drug levels in the body fluids always vary. For investigation of the kinetics of the antimicrobial effect of antibiotics at their varying levels, a universal dynamic system providing in vitro simulation of the pharmacokinetic profiles of the drugs in blood and tissues was developed. The system is based on the controlled dilution of the medium containing an antibiotic and microbial cells. the dynamic system allows simulation of any kinetic profile of the drugs with regard to the constants of the linear pharmacokinetic N-compartmental model. The trial of the dynamic system as applied to the antimicrobial effect of sisomicin on strain A 20 363 of E. coli revealed significant differences in the effect of the drug, when its bioexponential pharmacokinetic profile was simulated in a one-compartmental model with exponential absorption and a constant concentration of the antibiotic. The check determinations of the antibiotic concentration in the main flask of the system showed that the system provided high accuracy simulation of the required antibiotic levels.

Dose-Response Relationship, Drug↗
PubMed1985

[Kinetics of the antimicrobial effect in a dynamic system: the microcalorimetric recording method and choice of parameters for characterizing kinetic curves].

The kinetics of the in-vitro antimicrobial effect of sisomicin on E. coli, A 20363 was studied microcalorimetrically in a dynamic model simulating the pharmacokinetic profiles (intramuscular administration in a dose of 1 mg/kg) of the antibiotic obeying the one-compartmental model with first-order absorption. The microcalorimetric method was more accurate than the count of the colony forming units (CFU). Unlike the CFU method, it permits continuous recording of the process and unlike the turbidimetric method, it is more sensitive and selective. For quantitative characteristic of the curves of the antimicrobial effect kinetics it is suggested to use a new parameter, the effect duration (Td) which is determined by the difference in the moment of the antibiotic administration into the dynamic model (Tin) and the moment (Tout) when the rate of heat production or the number of the CFU or the optical density during the microbial secondary growth was the same as that at Tin. It was shown that the values of Td estimated in experiments with recording of the antimicrobial effect by different methods are similar. Evaluation of Td may be useful in predicting the optimal dosing intervals.

Calorimetry↗
PubMed1985

[Decrease of sisomicin nephrotoxicity as affected by cephalothin: pharmacokinetic evaluation].

The effect of cephalothin on the nephrotoxicity and pharmacokinetics of sisomicin was studied on Wistar rats. Sisomicin was injected intramuscularly in doses of 12.5 and 25 mg/kg alone or in combination with cephalothin in a dose of 360 mg/kg once a day for 16 days. It was shown that the combined use of sisomicin and cephalothin resulted in less pronounced functional and morphological changes in the kidneys as compared to the use of sisomicin alone. The decrease in the nephrotoxic effect was accompanied by a decrease in the sisomicin concentration in the blood serum and the site of the nephrotoxic effect (the kidney cortical layer) and the period of the aminoglycoside half-life in the kidney cortical layer under the action of cephalothin. The analysis of the relation between the nephrotoxic effect and the concentration of sisomicin in the kidney cortical layer and blood serum demonstrates that the nephrotoxicity of the sisomicin combination with cephalothin is mainly due to a decrease in the aminoglycoside concentration in the zone of the nephrotoxic effect.

Animals↗
PubMed1985

[Pharmacokinetics of the new antitumor antibiotic reumycin in an experiment: the prediction of the human pharmacokinetic profiles].

The reumycin pharmacokinetics was studied with HPLC on Wistar rats after intravenous injection of the antibiotic in single doses of 2.5, 5 and 10 mg/kg and after its oral administration in single doses of 5 and 10 mg/kg. It was shown that the reumycin pharmacokinetics within the above dose ranges was nonlinear and within every dose could be described by a two-compartmental model. Its nonlinear nature might be associated with saturated binding of the antibiotic by the blood serum proteins. The absolute extent of the reumycin bioavailability after oral administration was 50 per cent. The variability of the reumycin cumulative renal excretion was due to bimodality of distribution of the parameter in the animals. Renal excretion of the intact antibiotic decreased from 35 to 20 per cent with increasing of the dose. The value of the reumycin half-life in humans was predicted (41-46 hours) with the pharmacokinetic animal scale-up.

Animals↗
PubMed1985

[Pharmacokinetics of sisomicin during hemosorption and hemodialysis].

The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency. The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis. In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature. It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant). In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated. Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption.

Acute Kidney Injury↗