Biomedical subjects

A A Firsov

Publications and source records attributed to A A Firsov.

At least 19 recordsLinked to original sources

PubMed1992

[Age-related characteristics of ceftazidime pharmacokinetics in children].

To reveal possible age-dependent variations in the ceftazidime pharmacokinetics, the drug plasma concentrations were determined by HPLC in 10 children aged 2 to 13 years with peritonitis. The blood specimens were collected 0.25, 0.5, 1, 3, 6 and 8 hours after intravenous bolus administration of ceftazidime (Kefadym, Eli Lilly) in a single dose of 20 mg/kg. The mean values of the model-independent parameters were: total clearance (Cl), 3.3 +/- 0.8 ml/min.kg; steady-state distribution volume, 0.32 +/- 0.06 ml/kg; mean residence time, 1.7 +/- 0.4 hours. The C-coordinate of the gravity center was equal to 26 +/- 7 mg/l. A noticeable age-dependent decrease in Cl was detected by comparing the Cl estimates in our study for the children aged 7.0 +/- 3.0 years with earlier findings in children aged 12 years as well as in adults (18 and 26 years) and elderly patients (77 years): 2.5, 2.2, 2.0 and 1.1 ml/min.kg, respectively. A similar trend was observed for the ceftazidime volume of distribution (Varea). Due to the described reduction in Cl and Varea the age-induced changes in the half-life of ceftazidime were negligible. The age-dependent differences in ceftazidime pharmacokinetics should be taken into account in designing rational dosage regimens for the drug administration.

Adolescent↗

PubMed1991

[A pharmacokinetic basis for schedules for administering amikacin to newborn infants].

The use of correlations between the pharmacokinetic parameters and the patient's factors is one of the most promising trends in the elaboration of the efficient regimens of dosage. To establish the analogous correlations in terms of specifying the causes of the widely known individual variability of serum aminoglycoside concentrations in 139 neonates given amikacin for suggested or documented infections, a study was made of the drug pharmacokinetics.

Aging↗

PubMed1991

[Microcalorimetric study of the kinetics of the antibacterial effect of third generation cephalosporins in an in vitro dynamic system].

The antimicrobial effect (AME) kinetics of cefotaxime and ceftizoxime was studied with respect to 4 bacterial strains (E. coli, S. aureus, K. pneumoniae and P. aeruginosa) in an in vitro dynamic model. The mean integral concentrations, i.e. the AUC values divided by the dosing interval observed in blood of humans after the drug single intravenous administration in doses of 0.25, 0.5, 1 2 and 4 g. were simulated. The simulated concentrations of cefotaxime and ceftizoxime were 6.25 and 6.75, 12.5 and 13.5, 25 and 27, 50 and 54 and 100 and 108 mg/kg, respectively accounting for the differences in their pharmacokinetics. The changes in the microbial count were recorded microcalorimetrically by the rate of heat output with the BioActivity Monitor LKB 2277-202. The AME was expressed by TE reflecting the shift of the microbial growth curve in the presence of the cephalosporins against the control growth curve (in the absence of the drugs). It was noted that in simulating the concentrations observed after the drugs administration in various doses cefotaxime was mainly superior to ceftizoxime in terms of the TE, the value of the TE correlating with the respective values of the MICs. Some discrepancies between the TE and MICs were explained by the complicated shape of the TE vs. concentration or AUC curve observed earlier in regard to cefotaxime as well as by the differences in the steady state and dynamic conditions of the experiment.

Calorimetry↗

PubMed1991

[Pharmacokinetic monitoring during aminoglycosides: optimal therapy method of individual amikacin dosing].

One of the most successful approaches to adjustment of dosage regimens on the basis of single determinations of drug contents in blood specimens provides the blood sampling at the "ideal" moment (t*), i. e. at the time equal to the inverse value of the elimination rate constant. The above version of the one-point method is applicable to drugs obeying the one-compartment model. In practice, however, it is never known a priori whether the individual pharmacokinetic profile (PKP) is monoexponential or not. An attempt was made to apply the one-point method to individual amikacin (Am) intravenous bolus dosing in 27 patients with PKPs described not only by mono- but also by biexponential equations. The individual doses (Dc) estimated on the basis of Am concentrations recorded at the "ideal", point (2.75 hours after the administration) by the equation Dc = Dp.Cp(t*)/Ci(t*) were compared to the doses (DCl) found on the basis of greater than or equal to 4 determinations of the Am concentration (within 0.5 to 6 hours after the administration), i. e. by the equation DCl = Dp.Cli/Clp, where: Dp is the population value of an Am dose (7.5 mg/kg); Cp (t*) is the population value of an Am concentration at t* (6.7 mg/l), Clp is that of the total clearance [81.2 ml/(h.kg)] and Ci (t*) and Cli are the individual values of an Am concentration and clearance, respectively. The correlation coefficient of the DCl vs. Dc estimates was equal to 0.87. In 17 patients with monoexponential PKPs it was higher (r = 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗

PubMed1991

[Pharmacokinetic monitoring of aminoglycoside therapy: an optimal method of administration of individualized doses of gentamicin and sisomicin].

One of the most promising approaches to design the optimal schedule for TDM provides a single determination of a drug content in the blood specimen being collected at the "ideal" sampling time equaled to the inverse value of the elimination rate constant. Three versions of the one-point method when the specimen was collected at the "ideal" time point (3 h after a single i.m. drug administration), as well as at the times of "maximum" (1 h after injection) and "minimum" (6 h after injection) concentrations were compared by the retrospective analysis of the routine TDM data obtained with HPLC-techniques in 47 patients treated with gentamicin or sisomicin. As optimal individualized doses were considered ones calculated on the base of three subsequent determinations of the aminoglycoside concentrations, i.e. 1, 3 and 6 h after injection, and the estimation of individual clearance values (Cli). The optimal doses (DCl) were calculated according to equation DCl = Dp.Cli/Clp, where Dp and Clp are population values of the dose (1 mg/kg) and Cl 72.4 ml/(h.kg), respectively. The approximate values of the individual doses (D) were calculated according to equation D = Dp.Cp/Ci, where Ci is the individual drug serum concentration 1, 3 or 6 h after administration and Cp is the corresponded population value (4.8, 1.9 and 0.8 mg/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗

PubMed1991

Age dependence of erythromycin rectal bioavailability in children.

Erythromycin pharmacokinetics was studied in neonates (less than 1 month), infants (1-12 months) and other children (1-12 years) after the drug rectal and intravenous administration. The areas under the erythromycin serum concentration-time curves (AUC) were practically independent on children's age following the intravenous drug administration, but not its rectal administration. There was a distinct age dependency of the AUC parameter in the latter case. The increase of children's age was resulted in enhancement of the erythromycin total clearance, reduction of the steady-state volume of distribution and of the mean residence time. The extent of absolute bioavailability of rectally administered erythromycin was increased from 28 per cent in neonates to 36 per cent in infants and to 54 per cent in children greater than 1 year. Alteration of the mean absorption time parameter was reflected the delayed absorption of erythromycin in neonates.

Administration, Rectal↗

PubMed1991

Correlations between aminoglycoside pharmacokinetic parameters and patient's factors: from statement to implication for individual dosage design.

Amikacin pharmacokinetics was studied in 20 critically ill patients after a single i.v. bolus dose (500 mg). The amikacin pharmacokinetic profiles were characterized by marked intra-individual variability. Stepwise multivariate regression analysis made it possible to establish statistically significant correlations between the amikacin total clearance (Cl) and 8 patient's factors such as the, age, sodium plasma content, plasma osmolarity, partial pressure of oxygen and carbon dioxide, volumes of transfused plasma and blood, application of artificial lung ventilation (r2 = 0.98). The multiple regression equation for the Cl prediction provides reliable indirect estimation of the parameter. Thus, it appears possible to adjust the aminoglycoside dosage by taking into account 8 patient's factors, until the amikacin plasma concentration, time data are available.

Adult↗

PubMed1991

In vitro simulated pharmacokinetics profiles: forecasting antibiotic optimal dosage.

Sisomicin (SMN) and cefotaxime (CTX) antimicrobial effect (AME) kinetics were studied under in vitro stimulation the drug monoexponential pharmacokinetic profiles mimicking normal and impaired elimination of SMN or CTX administered in various doses to humans. Similar general shape of the AME intensity or duration vs the SMN and CTX AUC curves, i.e. the appearance of the "bacteriostatic" and "bactericidal" phases, was established irrespective of the antibiotic elimination rate. At the same time the AME vs AUC curves simulated normal and delayed drug elimination did not match. Thus, AME is defined not only the AUC value but also the peculiarities of the pharmacokinetic profile and, subsequently, the term of "antibiotic efficient concentration" is unseparable of the pharmacokinetic profile.

Anti-Bacterial Agents↗

PubMed1991

[Pharmacokinetics of protegentin, a combined preparation].

Protegentin is a combined preparation in the form of ointment containing 0.1 per cent of gentamicin, 0.25 per cent of erythromycin and 0.1 per cent of protease C. Pharmacokinetic studies on the preparation were conducted. Protegentin and gentamicin ointment, currently manufactured in this country, were applied to the surface of experimental pure cutaneous wounds in guinea pigs in a dose of 1 g. It was shown that inspite of the same contents of gentamicin in the ointments, the mean maximum concentration of the antibiotic in the underlying muscular tissue after the protegentin application was somewhat higher than that after the use of the gentamicin ointment. The differences in the drug concentration maintained during the whole observation period of 24 hours. However, they were not statistically significant. The gentamicin concentrations in serum after the use of protegentin were also somewhat higher than those after application of the gentamicin ointment (the differences were not statistically significant). Still, in no case the concentrations reached the potentially toxic ones. The erythromycin concentrations in the muscular tissue were much higher than those in the blood.

Animals↗

PubMed1991

[Erythromycin pharmacokinetics in children after rectal and oral administration].

Pharmacokinetics of erythromycin base was studied clinically in children not older than 14 years treated with new children dosage forms of the antibiotic i. e. 0.1 and 0.25 g enteric coated tablets and 0.06 and 0.125 g suppositories. It was noted that the new dosage forms were characterized by higher availability which was 2.5-3 times higher than that after using the erythromycin base tablets without the coating. Systematic increasing of erythromycin availability after the use of the rectal suppositories was observed with increasing of the children age. Absolute absorption in newborns, sucklings and children over 1 year amounted to 28, 36 and 54 per cent respectively.

Administration, Oral↗

PubMed1990

Quantitative analysis of antimicrobial effect kinetics in an in vitro dynamic model.

Variants of the available methods for estimating antimicrobial effect kinetics in an in vitro dynamic model were analyzed. Two integral parameters characterizing antimicrobial effect duration (TE) and intensity (IE) are suggested to define and analyze the concentration-effect relationships in these models, irrespective of the method of recording. TE is defined by the time from the moment of antibiotic administration to the movement when the bacterial count again reaches its initial level. IE is defined by the area between the microbial growth curves in the presence and absence of an antibiotic. TE and IE were used to quantify the antimicrobial effects of sisomicin on Pseudomonas aeruginosa 58, Escherichia coli 93, and Klebsiella pneumoniae 5056, simulating the pharmacokinetic profiles of the drugs observed following intramuscular administration in therapeutic doses, including the variability of aminoglycoside concentrations in human blood.

Anti-Bacterial Agents↗

PubMed1990

[Individualization of the amikacin administration regimen on the basis of the relationship between its pharmacokinetics and the patient's status].

Dosage individualization based on quantitative relationships between pharmacokinetic parameters and anatomophysiological and/or pathological factors, patient's factors (PFs) is of importance in designing optimal regimens. Unfortunately, the attempts to correlate aminoglycoside pharmacokinetic parameters and PFs often failed perhaps due to insufficient numbers of PFs under investigation. That is why we sought to involve more PFs, especially nontraditional ones, for explaining intersubject variability of the amikacin model-independent parameter in 20 patients with purulent inflammatory processes. Amikacin plasma concentrations in specimens collected 0.5, 1, 2, 4, 5 and 6 hours after the drug administration (500 mg, i.v.) were determined with the FRIA-technique (TDx, Abbott). The mean values of the total clearance (Cl), steady-state volume of distribution (Vss) and the mean residence time (MRT) were 87.5 +/- 18.4 ml/(h.kg), 0.33 +/- 0.07 l/kg and 4.0 +/- 0.6 h, respectively. Stepwise multivariate regression analysis made it possible to establish statistically significant correlations between the Cl and 8 PFs, including age, sodium plasma concentrations, plasma osmolarity, partial pressure of oxygen and carbon dioxide, volumes of transfused plasma and blood and artificial pulmonary ventilation (r = 0.99), as well as between the MRT and 6 PFs, including sex, plasma osmolarity, plasma creatinine concentrations, volumes of transfused plasma and artificial pulmonary ventilation (r = 0.94). Multiple correlations were also found between the area under the drug concentration/time curve and 11 PFs (r = 0.99). The coefficient of the multiple correlation between the Vss and volume of the transfused plasma proved to be much lower (r = 0.67). The multiple regression equation for the Cl prediction provided a reliable indirect estimation of the parameter individual values without the amikacin concentration data. Thus, it appeared possible to adjust the aminoglycoside dosage by taking into account 8 PFs before the TDM data were available.

Adult↗

PubMed1990

[Hypotension caused by intravenous infusion of rifampicin and its relation to the administration schedule].

It was shown in studies on animals that bolus administration of rifampicin induced hypotension whose severity depended on the rate of the antibiotic administration. When the antibiotic was administered in the 5-, 10- or 15-minute regimen in a dose of 10 mg/kg the maximum decrease in blood pressure was 44, 34 or 21% of the initial level and the maximum antibiotic concentration attained in the blood was 34.4, 27.2 or 22.6 micrograms/ml, respectively. With the infusion for 30 minutes, the maximum antibiotic concentration in the blood was 17.6 micrograms/ml and the blood pressure did not undergo any significant changes. When the rate of the antibiotic infusion was high there was pharmacokinetic heterogeneity of the blood serum and biophase which could lead to unpredictable results. After repeated administrations of rifampicin to the same animals pronounced tachyphylaxis to the antibiotic was noted, which manifested itself in decreasing of hypotension, though the serum antibiotic level was 1.5 to 2 times higher that the initial one. It was concluded that administration of rifampicin in the therapeutic dose equal to 10 mg/kg for 30 minutes was the most sparing regimen for the antibiotic bolus intravenous infusion. Gradual increase in the antibiotic dose and administration rate in patients is possible under careful control of blood pressure and pharmacokinetic studies.

Animals↗

PubMed1989

A dynamic model for in-vitro evaluation of antimicrobial action by simulation of the pharmacokinetic profiles of antibiotics.

The general principles of in-vitro simulation of drug pharmacokinetic profiles for linear one-, two- and multi-compartment models are described. An in-vitro dynamic model constructed on the basis of these, incorporating a novel filtration unit to provide efficient filtration of drugs at constant inoculum size, was used to study the antimicrobial action of sisomicin on Escherichia coli A 20363, in conditions simulating the pharmacokinetic profile observed in humans after a single intramuscular dose of 1 mg/kg.

Anti-Bacterial Agents↗

PubMed1989

[Kinetics of the antibacterial effect of ampicillin and sulbactam combinations in dynamic and static conditions].

Kinetics of antimicrobial effect (AME) of ampicillin/sulbactam combinations (ratios of 4:1 to 1:2) on ampicillin resistant bacterial strains producing beta-lactamases of types II, III, IV and V according to Richmond classification was studied with using the computerized system MS-2 (turbidimetric recording) and an in vitro dynamic model (microcalorimetric recording). The concentrations of the drugs in system MS-2 (static conditions) corresponded to the maximum ones observed in serum of humans after bolus intravenous administration of ampicillin in a dose of 0.5 g and sulbactam in doses of 0.125 to 0.5 g. The pharmacokinetic profiles of the drugs observed in the human serum after their oral and intravenous administration and in the tissue-chamber fluid after intravenous administration of ampicillin (0.5 g) and sulbactam (0.125 g) were simulated in the dynamic model. The combination efficacy was estimated with using the parameter of AME duration (TE) reflecting shifts in the curves of the microbial regrowth in the presence of the drugs against the curve of the control growth (in the absence of the drugs) and the parameter of the AME intensity (IE) evaluated by the area between the curves. It was noted that increasing of the ampicillin/sulbactam ratio from 1:4 to 1:1 was accompanied by an increase in the AME. Further increasing of the sulbactam content in the combination did not result in higher AME. For combined ampicillin/sulbactam dosage forms the ratios of 1:1 to 2:1 should be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1989

[Pharmacokinetic monitoring of antibiotic therapy].

The general strategy in optimization of antibiotic dosage regimens included development of population or common regimens for an "average" patient (the 1st approximation), subpopulation regimens for patients of certain categories on the basis of interactions between the pharmacokinetic parameters and "patient factors" (the 2nd approximation) and individual regimens on the basis of the data of the pharmacokinetic monitoring (the 3rd approximation). Characteristics of every of the approximations in antibiotic therapy of adults and children were analyzed. Out of the peculiarities of the strategy use in pediatrics+ and micropediatrics+ the following should be indicated: (1) pharmacokinetic heterogeneity of the population requiring grouping of the patients and consequently development of subpopulation dosage regimens omitting stage I, (2) possible development of dosage regimens on the basis of the ration between the pharmacokinetic parameters or immediate drug concentration values and the "patient factors" not only in chronic but also in transitory impairment of some functions and (3) the necessity of considering systematic changes in "pharmacokinetic status" of every child during individualization of the dosage regimens by the data of the pharmacokinetic monitoring.

Age Factors↗

PubMed1989

[Pharmacokinetics of azlocillin in critical conditions: an individualized schedule of drug administration in relation to anatomo-physiologic and pathologic factors].

Azlocillin pharmacokinetics was studied after a single intravenous injection of the antibiotic in a dose of 4 g in 20 patients in critical state. To elucidate the causes of significant individual variability of the antibiotic pharmacokinetics observed in the patients, multiple correlation analysis of the main pharmacokinetic parameters i. e. the area under the concentration/time curve, total clearance, steady-state volume of distribution and mean residence time was performed in regard to the "patient factors" such as sex, age, the volumes of transfused liquid, blood, plasma and blood substitutes, hemoglobin levels, erythrocyte count and ESR. Adequate correspondence of the predicted by the "patient factor" values of the areas under the concentration/time curve and the total clearance to the actually determined values was observed. Correspondence of the predicted values to the steady-state volume of distribution and the mean residence time to the actually determined values was satisfactory. A procedure for design of azlocillin individual dosage regimens based on calculating individual clearance by the "patient factors" is described.

Azlocillin↗

PubMed1989

[Individual schedule of administration of aminoglycosides with reference to anatomo-physiological and pathological factors].

Potentiality of designing individual dosage of sisomicin and gentamicin in regard to "patient factors" was estimated. 62 adult patients with various pulmonary diseases at the background of volemic disorders of diverse degrees were treated with the aminoglycosides under monitoring of their blood levels. Concentrations of sisomicin and gentamicin in serum 1, 3 and 6 hours after their single administration in a dose of 1 mg/kg were determined by HELC. The antibiotic pharmacokinetics was characterized by pronounced individual variability. The ratio of the difference between the upper and lower confidence limits to the average values of the steady-state volume of distribution, the total clearance and the mean residence time amounted to 70, 60 and 57 per cent respectively. To elucidate the cause of the variability multiple correlation analysis of the pharmacokinetic parameters by the "patient factors" was performed. The highest coefficient of the multiple correlation (r = 0.690) defined relation between the aminoglycoside concentration 1 hour after the injection and the hematocrit, globular volume and phase of the volemic disorders which was expressed in coded variables. The coefficient of the multiple correlation between the total clearance and the body surface area, concentrations of creatinine and urea in serum, hematocrit, circulating blood volume and the phase of the volemic disorders was equal to 0.439. Therefore, the consideration of the above factors allowed to explain only 20 per cent of the observed individual variability of the pharmacokinetic parameters. In this connection mediated prediction of total clearance and subsequently individual dosage of the aminoglycosides by the "patient factors" was expedient only until the primary data on the pharmacokinetic monitoring were obtained.

Adolescent↗