A városi tipizálás, a gazdasági növekedés és a járműipar főbb összefüggései Kelet-Közép-Európában = Main Correlation of the City Structures, Economic Growth and Automotive Industry in Central and Eastern Europe

Napjainkban a városkutatások reneszánszát tapasztalhatjuk, a városok a regionális és országos gazdasági növekedés, a fejlődés és a versenyképesség gócpontjai, amelyben igen koncentráltan zajlanak a térbeli folyamatok. Ezen kijelentést alapul véve, a dolgozat célja összetettnek tekinthető. Egyrészt röviden be kívánja mutatni a napjainkban is átalakulóként jellemezhető kelet-közép-európai térség speciális területi egyenlőtlenségeit, a városokat és városias térségeket. További célként a különböző városias térségtípusok, a járműipari központok és a gazdasági növekedés összefüggéseinek kimutatását határoztuk meg. Konvergencia vizsgálatunk világosan bebizonyította, hogy az autóipari központok városai hozzájárulnak Kelet-Közép-Európa térségi gazdasági- és térségi dinamikáihoz

Rapid and sensitive ultra-high-pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study

Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters (R) Acquity UHPLC system equipped with a UV-vis detector was employed. The method was established using an Acquity (R) UHPLC HSS SB C-18 protected by an Acquity (R) UHPLC HSS SB C-18 VanGuard guard column and detection at 324 nm(.) The mobile phase consisted of ultrapure water-acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 L, and the run time was just 2 min. The samples were kept at 25 degrees C until injection and the column at 45 degrees C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15-20 mu g/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

A review of pharmacokinetic parameters of metabolites and prodrugs

In drug discovery and development, the kinetic study of active metabolites plays an important role, helping to define the time course of the drug in the body and its activity or toxicity. After a pharmacokinetics assessment of a drug and its metabolite or a prodrug and its parent-drug, several parameters can be calculated. In some cases, achieving the objective of the study does not require all possible parameters to be calculated. When parameters are calculated, it is essential that their denotations are widely accepted and used. However, some parameters undergo a certain variability of denotation, which may confuse some readers. Thus, this review summarizes the current published data for experimental pharmacokinetic parameters of metabolites and the calculations involved in simple metabolite pharmacokinetic studies. It also evaluates the most common pharmacokinetic parameters in the literature and suggests metabolite parameters that could be determined to help advance metabolite kinetic models

Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol

Abstract Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment

Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy

Since 1966, rifampicin (RIF) has been considered one of the most potent drugs in the treatment of tuberculosis (TB), which is caused by infection with M. tuberculosis (Mtb). New nanostructured formulations for RIF delivery and alternative routes of administration have been studied as potential forms of treatment. This study evaluates a liquid crystal system for RIF delivery, using alternative drug delivery routes. The systems developed are composed of surfactant, oleylamine, and soy phosphatidylcholine. With the aid of polarized light microscopy, it was possible to determine that the developed systems had a hexagonal mesophase. All systems developed showed non-Newtonian pseudoplasticity and a high degree of thixotropy. Liquid crystal systems with RIF showed an increase in elastic potential, indicating greater mu-coadhesiveness. The evaluation of mucoadhesive forces revealed an increase in the mucoadhesive potential in the presence of mucus, indicating the presence of satisfactory mucoadhesive forces. The 9DR and 10DR liquid crystal systems, when submitted to Differential Scanning Calorimetry analysis, remained structured even at temperatures above 100 °C, showing excellent stability. The developed liquid crystal systems showed a tolerable degree of cytotoxicity and bactericidal potential, for example, the 9DR system demonstrated a reduction in bacterial load after the third day and reached zero CFU on the seventh day of the test. The developed systems were also evaluated in the preclinical model of Mtb-infected mice, using the nasal, sublingual, and cutaneous route for the delivery of RIF associated with a nanostructured liquid crystal system as a possible tool in the treatment of TB

Temporal profile of (A) coumarin, (B) 7-hydroxicoumarin and (C) <i>o</i>-coumaric acid plasma concentrations in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with different amounts of coumarin.

<p>Temporal profile of (A) coumarin, (B) 7-hydroxicoumarin and (C) <i>o</i>-coumaric acid plasma concentrations in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with different amounts of coumarin.</p

Temporal profile of the mean plasma concentrations of coumarin, 7-hydroxycoumarin and o-coumaric acid in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with 1500 mg of coumarin.

<p>Temporal profile of the mean plasma concentrations of coumarin, 7-hydroxycoumarin and o-coumaric acid in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with 1500 mg of coumarin.</p

Temporal profile of (A) coumarin, (B) 7-hydroxicoumarin and (C) <i>o</i>-coumaric acid plasma concentrations in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with different amounts of coumarin.

<p>Temporal profile of (A) coumarin, (B) 7-hydroxicoumarin and (C) <i>o</i>-coumaric acid plasma concentrations in human volunteers receiving oral administration of 60 mL of guaco syrup spiked with different amounts of coumarin.</p

Metabolism of coumarin in humans via 7-hydroxylation and possible route via hydrolysis of the lactone ring.

<p>Metabolism of coumarin in humans via 7-hydroxylation and possible route via hydrolysis of the lactone ring.</p

Representative HPLC-MS/MS chromatograms of human plasma spiked with standards of coumarin, 7-hydroxycoumarin, <i>o</i>-coumaric acid, kaurenoic acid and the internal standards 6-methylcoumarin, isoferulic acid and prednisone.

<p>Data: signals not smoothed; sample prepared at MQC concentration level.</p