PubMed Health⌕ Search

Biomedical subjects

V K Piotrovskij

Publications and source records attributed to V K Piotrovskij.

8 recordsLinked to original sources
PubMed1994

Modeling of the saturable time-constrained amoxicillin absorption in humans.

Amoxicillin pharmacokinetics was modeled using a two-compartment disposition model and a saturable time-constrained absorption model with a storage compartment. The absorption model parameters estimated by the nonlinear regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1, range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range: 703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median: 1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median: 1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h, range: 0-0.123 h). It was shown, that the first-order absorption parallel to the saturable process is negligible in the dose range studied. The model described well the dependence of areas under concentration-time curves on the dose determined in several earlier studies. It was used also to predict the fraction of the amoxicillin dose absorbed for different doses. Simulations performed over a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the duration of the absorption period.

Absorption↗
PubMed1994

The use of physiologically based models to simulate enantioselective differences in pharmacokinetics.

The majority of synthetic drugs are chiral and are usually administered as racemates. However, body proteins can recognize the steric configuration, and the pharmacological activity and pharmacokinetics of enantiomers usually differ. The key parameters that determine the overall enantioselectivity in disposition are those quantifying protein binding and biotransformation of drugs. Physiologically based models (PBMs) are effectively applied to predict pharmacokinetics of drugs using those parameters. In this work we used PBM to evaluate a range of changes in the model-independent pharmacokinetic parameters (total clearance, mean residence time, volume of distribution, half-life) with changing relative fraction of enantiomers unbound in the blood (range 1-8) and relative intrinsic hepatic clearance (range 1-10). A pharmacokinetic interaction between enantiomers was also simulated and it was shown that experiments with separate administration of pure enantiomers and of a racemate are equally important to avoid biases in pharmacokinetic parameter estimates due to interactions between enantiomers. Concentration-effect relationships were analyzed for the case of one enantiomer being active, and it was demonstrated that hysteresis as well as proteresis may appear depending on the differences in hepatic intrinsic clearances of enantiomers or fractions unbound in blood. The great predictive potential of physiologically based models in stereopharmacokinetics was thereby demonstrated.

Computer Simulation↗
PubMed1993

The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man.

A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA.

Adult↗
PubMedDate not supplied

Pharmacokinetics of acetylsalicylic acid and its metabolites at low doses: a compartmental modeling.

The pharmacokinetics of acetylsalicylic acid (ASA) and its metabolites salicylic acid (SA) and salicyluric acid (SUA) were studied in 12 healthy young volunteers after oral administration of low (30 and 100 mg) and moderate (400 mg) doses. Plasma and urine were assayed for the above drugs by high-performance liquid chromatographic method. Individual pharmacokinetic parameters were estimated by compartmental modeling (ASA and SA) and by model-independent methods (SUA). ASA parameter values estimated in this study were in agreement with those reported by other authors after administration of higher doses, which confirms the linearity of ASA pharmacokinetics in a broad dose range. On the contrary, both metabolic and renal elimination routes for SA were found to be saturable. The relative changes in SA renal clearance with the dose were more pronounced than those in metabolic clearance. Particularly, there was no statistically significant difference in SA metabolic clearance between 30 and 100 mg doses, indicating the linear kinetics in this dose range. Further increase in the dose resulted in significant decrease in SA metabolic clearance. At the same time, both SA excretion rate constant and fraction excreted significantly diminished across the entire dose range studied. The dependence of SUA renal clearance upon the dose was shown to be complex, reflecting possible saturability of its excretion.

Administration, Oral↗