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Veljko Todorović

Publications and source records attributed to Veljko Todorović.

4 recordsLinked to original sources

A pharmacokinetic comparison of three pharmaceutical formulations of nimesulide in healthy volunteers.

BACKGROUND/AIM: Switching the patient from one pharmaceutical formulation of the same drug to another, may lead to therapeutic inadequancy in some cases. To minimize the risk, careful pharmacokinetic studies are desired in the pre-registration period and afterwards. METHODS: A randomized, crossover design with one-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 15 hours, were analyzed for nimesulide content by a high-performance liquid chromatographic method with ultraviolet (LU) detection. The pharmacokinetics and relative bioavailability of three different pharmaceutical formulations containing nimesulide, manufactured by the same pharmaceutical factory, were studied prospectively in 12 healthy subjects of both sexes. A single 100-mg oral dose of nimesulide was given to the volunteers in the form of conventional tablets, mouth dissolving tablets or as a suspension. Analysis of variance, power analysis, 90% confidence intervals, and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. RESULTS: The tolerability of all preparations was excellent. The respective confidence intervals of the ratios of geometric means of C(max) and AUC(0-infinity) of nimesulide were out of acceptable limits either for conventional tablets in comparison with suspension or for mouth dissolving tablets when compared with conventional tablets. A comparison of mouth dissolving tablets with suspension showed a statistically significant difference between C(max) values (suprabioavailability of mouth dissolving tablets), while the point estimate of the ratio of geometric means of AUC(0-infinity) was 0.945 with the corresponding 90% confidence interval of 0.902-0.991. At the 5% level of significance, there were no differences between the formulations under the study in times elapsed to peak serum concentrations, as revealed by the non-parametric Wilcoxon signed ranks test. CONCLUSION: Only a 90% confidence interval for the relative differences of log-transformed AUC(0-infinity) values of nimesulide absorbed from mouth dissolving tablets vs. suspension was included in the 80% to 125% interval proposed by the Food and Drug Administration (FDA). On that basis, mouth dissolving tablets (Nimulid-MD) were considered bioequivalent to Nimulid suspension according to the extent of drug absorption. Concerning the comparable amounts of nimesulide available in the systemic circulation after application of these formulations the one might not expect therapeutic failure after switching the patient from one to another.

Adult↗

Serbia National Poison Control Centre: organization and current activities.

Ministry of Health of the former Federal Republic of Yugoslavia established the National Poison Control Centre in 1995. However, that was only the formally solution since clinical, analytical and experimental services in toxicology had worked independently for at least 40 years. Besides the Headquarters, NPCC has currently 2 main units, the Clinic of Emergency and Clinical Toxicology and Pharmacology and the Institute of Toxicology and Pharmacology. The latter is consisted of Toxicological Information Department, Department of Analytical Toxicology and Department of Experimental Toxicology and Pharmacology. The Mobile Toxicological Chemical Unit is a separate department that is activated from personnel of the NPCC in a case of chemical accidents and/or disasters. Clinical, information and analytical parts of NPCC have a 365-day/24-hour working service. The Clinic of Emergency and Clinical Toxicology and Pharmacology is a place where the intoxicated patients are treated, including those that need the intensive care measures. Toxicological Information Department uses the data from a self-made computer Database for different information purposes. Department of Analytical Toxicology is equipped with a lot of contemporary analytical equipment that is giving the opportunity of identification and quantification of chemicals/metabolites/degradation products in biological material, food, water, air and soil. Basic pharmacological and toxicological research of chemicals and pre-clinical investigations of antidotes are realized in the Department of Experimental Toxicology and Pharmacology. In terms of medical prevention and rational treatment of human poison exposures in Serbia, the current organization of NPCC has so far proven to be effective.

Drug Information Services↗

[Acute phenol poisoning].

INTRODUCTION: Phenol (carbolic acid) is one of the oldest antiseptic agents. Currently it is used as a disinfectant, chemical intermediate and nail cauterizer. Phenol is a general protoplasmic poison (denatured protein) with corrosive local effects. Phenol derivates are less toxic than pure phenol. The lethal dose is between 3 to 30 g, but may be as little as 1 g. Phenol is well absorbed by inhalation, dermal application, and ingestion. MANIFESTATIONS OF ACUTE POISONING: Local manifestations. Dermal exposure produces lesions which are initially painless white patches and later turn erythematous and finally brown. Phenol produces mucosal burns and coagulum. They cause eye irritation and corneal damage. When ingested, it causes extensive local corrosions, pain, nausea, vomiting, sweating, and diarrhea. Severe gastrointestinal burns are uncommon and strictures are rare. Inhalation produces respiratory tract irritation and pneumonia. Systemic manifestations develop after 5 to 30 minutes postingestion or post dermal application, and may produce nausea, vomiting, lethargy or coma, hypotension, tachycardia or bradycardia, dysrhythmias, seizures, acidosis, hemolysis, methemoglobinemia, and shock. MANAGEMENT: Phenol poisoning requires immediate medical evaluation, in cases of significant phenol ingestion (more than 1 g for adults or 50 mg for infants) or symptomatic intoxication. It is necessary to establish and maintain vital functions and establish vascular access. Treatment includes the following: shock (fluids and dopamine), arrhythmias (lidocaine) and convulsions (diazepam). Health personnel should use gowns and rubber gloves. Inhalation of 100% oxygen is recommended. Intubate and assisted ventilation might be necessary. Metabolic acidosis should be managed by 1 to 2 mEq/kg of sodium bicarbonate. Methemoglobinemia should be treated if greater than 30%, or in cases of respiratory distress, with methylene blue 1 to 2 mg/kg of 1% solution, slowly i.v. If phenol is ingested, avoid emesis, alcohol and oral mineral oil and dilution, because they may increase absorption. Gastric lavage is usually not recommended. Immediate administration of olive oil and activated charcoal by small bore nasogastric tube is necessary. CONCLUSION: Apart from the abovementioned, immediately decontaminate the skin with copious amounts of water followed by undiluted polyethylene glycol. Wash the area thoroughly with soap and water after treatment. Immediately decontaminate the eyes with copious amounts of tepid water for at least 15 minutes. Follow up examination using fluorescein stain of eyes for corneal abrasion is recommended

Acute Disease↗

[Acute poisoning with cardiovascular agents].

In order to determine the frequency, severity of poisoning, and the efficacy of the applied therapeutic measures, retrospective study of 391 patients treated for acute drug poisoning was performed during one-year period at the Clinic for Emergency and Clinical Toxicology and Pharmacology. In 49 (12.5%) patients cardiovascular agents were the cause of poisoning, most frequently beta-blockers and calcium antagonists (77.5%). Poisoning with antihypertensive agents was registered in 12.2% of patients, antiarrhythmics in 8.2%, and cardiotonics in 2.1%. Beta-blockers and calcium antagonists caused severe poisoning in over 40% of cases. Predominant clinical manifestations were registered on cardiovascular system, while central nervous system effects occurred secondary to cardiotoxicity. Symptomatic and supportive measures were performed most frequently, while specific agents, glucagon, calcium salts, and others, were used less often.

Acute Disease↗