Biomedical subjects

R Karba

Publications and source records attributed to R Karba.

22 records · Page 2Linked to original sources

PubMed1979

Appropriate nitroxoline dosage regimen design.

Clinically used dosage regimen of nitroxoline, three times 100 mg daily, was proved to be inappropriate because the successfulness of medical treatment was rarely sufficient. Nitroxoline, used as urinary antiseptic, exhibits its antibacterial activity in concentrations higher than 6 mg/l, as demonstrated in many "in vitro" experiments. This work deals with the most appropriate nitroxoline dosage form as well as with the optimal dosage regimen design. The data were obtained by the aid of the suitable pharmacokinetic model and multiple dosing simulation on analog-hybrid computer EAI 580. From the several studied alternatives two usable dosage forms with the necessary dose and corresponding dosage interval were selected.

Anti-Infective Agents, Urinary↗

PubMedDate not supplied

The bioavailability of oral nifedipine formulations: a statistical and simulation approach.

The bioequivalence of three oral forms of nifedipine was assessed in a triple crossover study on 12 healthy volunteers. Single 10 mg dose was given and ten blood samples were drawn during the first 8 h after administration. Highly sensitive gas chromatographic method was used for the nifedipine assay. Pharmacokinetic parameters which describe bioavailability and general kinetic behaviour of the drug (AUC, Cmax, tmax, beta, MRT) were calculated from individual plasma profiles. They were subjected to statistical analysis (paired t-test, Hauck's inverted t-test, and Westlake's method of confidence intervals). Analogue-hybrid simulation and identification was used to generate plasma profiles of nifedipine after single and multiple dosing. Averaged plasma concentrations were used for this purpose. The three formulations studied were bioequivalent in terms of the rate of absorption. The simulation proved to be an efficient tool to substitute in vivo multiple dosing studies for assessment of bioavailability. The specific statistical methods should be preferred in bioequivalence data evaluation due to their greater power and inclusion of extraneous bioequivalence limits interval. Despite the differences among the formulations studied, each one of them should be viewed according to its intended clinical use.

Adult↗

PubMedDate not supplied

Formulation of controlled release microspheres containing nicardipine: the role of pharmacokinetic modeling and computer simulation.

Nicardipine is an antihypertensive drug of the dihydropyridine series. It has high solubility in an acidic and low solubility in an alkaline medium. It is rapidly absorbed, extensively presystemically metabolized and excreted in the urine and faeces, mainly as inactive metabolites. Since the duration of its action can be extended by prolonging the absorption interval, the design of controlled release formulation is reasonable. The aim of the present study was to prepare microspheres which would release nicardipine at a decreased rate in gastric and increased rate in intestinal juice during a 12 h interval. Pharmacokinetic modeling based on compartment analysis and supported by analog computer and digital simulation technique showed that the target steady state peak plasma concentrations of 32 microg/l and trough plasma concentration of 7 microg/l would be maintained if nicardipine were incorporated in a formulation releasing the drug as follows: 25% after 1 h, 40% after 2 h, 65% after 4 h, 80% after 6 h, 90% after 8 h and 100% by 12 h. Microspheres have been prepared from hydroxypropylmethylcellulose phthalate polymer using the solvent evaporation method. Drug content, scanning electron micrographs, particle size distribution and dissolution profile were determined. In vitro nicardipine release was described by a biphasic square root of time kinetics and was in accordance with the above values relating to the dissolution. Furthermore, a composed first-pass pharmacokinetic model with derived release function as an input was developed to predict nicardipine plasma concentrations after single- and 12 h multiple-dosage-regimen scheme administration of controlled release microspheres.

Antihypertensive Agents↗

PubMedDate not supplied

Pathways of paracetamol absorption from layered excipient suppositories: artificial intelligence approach.

When studying paracetamol availability after rectal administration, the differences between slower and faster release suppositories were discovered. Approach with modelling and simulation of compartment-based models was used to explore the differences. A study of paracetamol from layered excipient suppositories shows that many different mechanisms are involved in the drug pharmacokinetics. There is also a large number of articles, each dealing with only one or with a few of the mechanisms. However, there is little information available on how the mechanisms interact in the organism and thus govern the pharmacokinetics of the drug, which means that systemic view in the expert knowledge is missing. In the case of paracetamol rectal availability the use of partially fuzzyfied model allowed systemic combination of all described mechanisms found in the literature and measured data. In spite of non-identifiability, the model showed that patterns that explained differences in bioavailabilities of the two formulations of suppositories could be found. Results of modelling and simulation show that "in vivo" there is practically no difference in cumulative release profiles between the two formulations. However, due to higher content of mono-di-glycerides in a slower release formulation, the extent of absorption is augmented both by absorption-enhancing effect of mono-di-glycerides and the liver bypass mechanism via diminished viscosity.

Acetaminophen↗