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Biomedical subjects

R Karba

Publications and source records attributed to R Karba.

8 recordsLinked to original sources

Treatment of chronic wounds by means of electric and electromagnetic fields. Part 1. Literature review.

The healing of a cutaneous wound is accompanied by endogeneous electrical phenomena. Not knowing whether they represent merely a side-effect of the physiological processes which take course during healing or whether they play a much more important role as mediators of healing, externally applied electricity was examined as a therapeutic tool for the enhancement of natural regenerative processes. In the present review a historical literature survey dealing with human applications of electric current for wound healing acceleration is given. It presents a complete palette of heterogeneous studies, differing in the parameters of applied electric current, in delivery modes as well as in the types of wounds being stimulated. Because of all these differences, comparing the efficacy of the described methods is difficult and could hardly be objective. Therefore greater stress was laid upon the discussion concerning the problems in designing clinical studies (size of the sample observed, control group, ethics of the procedures), rationales for the employment and possible underlying mechanisms of particular methods, and problems of evaluating their efficacy. In spite of the extensive work performed in the field of electrical wound healing we remain only part way towards explaining the mechanisms by which electricity reinforces the regenerative capabilities of injured tissue as well as only part way towards the selection of the optimal stimulation method from among the published reports.

Chronic Disease

Urodynamic modeling of norfloxacin pharmacokinetics by means of computer simulation.

Urodynamic model was developed which, in conjunction with a compartmental pharmacokinetic model, was used for study of factors influencing drug concentrations in urine: urine flow rate, residual bladder urine, maximal bladder urine, stage of renal failure, and elimination kinetics of drugs. Norfloxacin (NOR) was used as a model drug, although the model haw general applicability for all urinary antiseptics. Pharmacokinetic data were obtained from a clinical study in which norfloxacin was administered orally as a single 400mg dose to four subjects with installed urine catheters. Sample of blood, bladder and catheter urine were collected and concentrations of NOR measured by a HPCL method. Modeling was performed on analog--hybrid computer EAI 580. Besides the fitting of model response to obtained in vivo data, simulations of expected clinical situations were performed in which the interplay of above mentioned factors was studied in terms of urine concentrations profiles. NOR treatment with 400mg b.i.d. secured sufficient urine concentrations in most studied cases. This approach should be applied for corresponding study of other urinary antiseptics, especially those with less favourable urinary levels.

Chromatography, High Pressure Liquid

Human skeletal muscle: phasic type of electrical stimulation increases its contractile speed.

Skeletal muscles, exposed to a prolonged period of specific functional demands, respond adaptively. Electrical stimulation, when employed as a technique for subjecting selected muscles to altered use, enables precise entrainment of the pattern of functional activity. In this investigation, the vastus lateralis muscle in a group of volunteers was stimulated. The stimulation program typical of a phasic type of activity (high frequency, high current amplitude, short pulse duration) intermittently subjected the stimulated muscles to brief periods of intense activity, followed by relatively long pauses. The activation-relaxation time ratio chosen was 1 to 13. It was determined to prevent the muscles from fatiguing. The effects of the chronic stimulation program were established by measurements of the time course of contraction and relaxation and fatigue of the vastus lateralis muscle. Chronic phasic electrical stimulation increased the speed of muscle contraction by 15% while the fatigue characteristics remained unchanged.

Electric Stimulation

Computer simulation of ciprofloxacin pharmacokinetics in patients on CAPD.

Continuous ambulatory peritoneal dialysis (CAPD) has become an accepted alternative to chronic hemodialysis in the treatment of end-stage renal disease. The method utilizes the diffusion of drugs from the blood through the peritoneal membrane to the peritoneal cavity if administered intravenously (IV) and perorally (PO) and in the opposite direction if applied intraperitoneally (IP). The present work uses an open, two-compartment pharmacokinetic model reversibly linked with the compartment representing the peritoneal cavity and an analog-hybrid computer to simulate drug levels in sampled and unsampled compartments under conditions of various routes of administration (IV, IP and sequential IV, IP and PO) and different clinical status (presence and absence of peritonitis). The drug chosen for simulation was ciprofloxacin (CIP), a new synthetic antibacterial agent of the 4-quinolone group. Eight patients were included in the study, and CIP concentrations in plasma and dialysate were obtained by HPLC analysis to assess the reliability of the model and the efficiency of the sequential dosing scheme. CIP plasma and dialysate levels were adequate for the majority of microbes causing CAPD peritonitis. The proposed regimen was efficient in 85% of cases.

Administration, Oral

Bioavailability of piroxicam: oral and rectal multiple application in humans.

The aim of the work is to evaluate the bioequivalence of piroxicam administered orally and rectally in 20 mg dose every 24 hours. The corresponding "in vivo" study was undertaken and plasma samples were collected during the ninth dosing interval. HPLC method was used for piroxicam plasma concentrations determination. AUC and C were calculated and the obtained data were statistically analyzed. Analog-hybrid simulation was used to confirm additionally the similarity between the discussed formulations. No significant differences were observed using paired t-test and two-way analysis of variance while the methods of Hauck and Westlake, looking strictly, gave nonbioequivalence. Simulated response of one compartment model is suitable for "in vivo" data in both cases. Measured and simulated average steady state concentrations are equal and in complete accordance with those given in literature. Finally it can be concluded that oral and rectal application are bioequivalent in the sense of expected clinical effects.

Administration, Oral

Clinical pharmacokinetics of nitroxoline.

14C-Nitroxoline was given orally to the rats, and its distribution as well as plasma and bile levels were determined autoradiographically and by the aid of radioactivity measurements, respectively. Nitroxoline was also given to the human volunteers orally and intravenously in three various doses and the corresponding urine concentrations of unconjugated and conjugated nitroxoline were determined spectrophotometrically. A pharmacokinetical model was generated on the basis of the results. The curve fitting procedure between total nitroxoline cumulative quantities in urine and the model response simulated on analog-hybrid computer enabled the evaluation of the validity of the chosen model as well as of the identification of its parameters.

Adult

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

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