Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.A bioequivalência média de duas formulações de levofloxacino disponíveis no Brasil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brasil, produto referência) e Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brasil, produto teste) foi determinada por meio da realização de ensaio aleatório, aberto, cruzado, com dois períodos e duas sequências, em 26 voluntários sadios em condições de jejum. Amostras de sangue dos voluntários foram obtidas ao longo de um período de 48 horas após administração de dose única de 500 mg de levofloxacino. As concentrações plasmáticas do fármaco foram determinadas por método cromatográfico validado. Os parâmetros farmacocinéticos Cmax, Tmax, Kel, T1/2el, AUC0-t e AUC0-inf foram calculados por análise não compartimental. A bioequivalência foi determinada pelo cálculo de intervalos de confiança 90% (IC 90%) para as razões entre os valores de Cmax, AUC0-t e AUC0-inf obtidos para os produtos teste e referência, usando dados transformados logaritmicamente. A tolerabilidade foi avaliada pelo acompanhamento dos sinais vitais e resultados de exames laboratoriais, por consultas e por relato espontâneo dos voluntários. ICs 90% para Cmax, AUC0-t e AUC0-inf foram 92.1% - 108.2%, 90.7% - 98.0%, e 94.8% - 100.0%, respectivamente. Os eventos adversos observados foram náusea e cefaleia. Concluiu-se que os produtos Tavanic(c) e Levaquin(c) são bioequivalentes, uma vez que os ICs 90% estão dentro da faixa de 80%-125% proposta pelas agências reguladora

コウベ トキワ タンキ ダイガク ガクセイ ニ オケル カコ 3ネンカン ノ ツベルクリン ハンノウ ケッカ ホウコク ト ソノ タイオウ ニ ツイテ

過去3年間391名の臨地実習開始前の学生を対象に神戸常盤短期大学で行ったツベルクリン反応検査(以下ツ反検査)の結果,2段階法を行った本年からは真の陰性者は平均2.6%に減じた。このツ反検査2段階法陰性者に対してBCG接種を施行することを学生に勧奨するとともに,強陽性者を含めた発赤長径30mm以上で硬結を有する学生に対しては医療機関受診を含めたこれからの対応および対策が重要になるものと考えられる

Bioequivalence evaluation of tinidazole 500 mg tablets

Tinidazol, 1-[2-(ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole, é um membro da classe dos nitroimidazóis que apresenta atividade amebicida, giardicida, tricomonicida e anaeróbica. O objetivo deste estudo foi avaliar a bioequivalência de duas marcas comerciais de comprimidos contendo 500 mg de tinidazol em voluntários sadios. O ensaio de bioequivalência entre o produto teste (Amplium® - FARMASA) e o produto referência (Pletil® - Pharmacia do Brasil Ltda) foi do tipo randomizado, cruzado e aberto. O medicamento foi administrado em dose única de 500 mg de tinidazol a 24 voluntários sadios. Amostras de sangue foram coletadas até 72 horas após a administração e analisadas através de método de cromatografia líquida de alta eficiência validado com detecção UV. As curvas médias de decaimento plasmatico obtidas para o produto teste (Amplium® - FARMASA) e para o produto referência (Pletil® - Pharmacia do Brasil Ltda) foram semelhantes, da mesma forma que os parâmetros farmacocinéticos Cmax (referência: 11,34 µg/mL; teste: 11,11 µg/mL), t<SUB.max (referência: 1,67 h; teste: 1,71 h), AUC0-t (referência: 201,92 µgxh/mL; teste: 198,15 µgxh/mL), AUC0-&#8734; (referência: 208,25 µg/mL; teste: 203,80 µgxh/mL) e t(½)el (referência = 14,05 h; teste = 13,91 h). A análise multivariada realizada através da análise de variância (ANOVA), para avaliação dos efeitos produto, grupo e período, revelou a ausência destes efeitos no estudo, indicando que o delineamento do estudo foi apropriado. Os valores do intervalo de confiança 90% para a razão de Cmax (93.9 % - 102.6 %), AUC0-t (94.9 % - 101.1 %) e AUC0-&#8734; (94.6 % -100.8 %) encontram-se entre 80 - 125 %, intervalo proposto pelo FDA e ANVISA. A comparação estatística dos parâmetros AUCo-t , AUC0-&#8734; e Cmax indicam claramente não haver diferença significativa entre os dois produtos contendo 500 mg de tinidazol. Baseado nos resultados farmacocinéticos e estatísticos deste, pode-se concluir que os dois produtos são bioequivalentes e podem ser considerados intercambiáveis na terapêutica.Tinidazole, 1-[2-(ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole, is a member of the 5-nitroimidazole class of antimicrobial agents with amoebicidal, giardicidal, trichomonicidal and anaerobic activity. The purpose of this study was to evaluate the bioequivalence of two brands of tinidazole 500mg tablets in healthy human volunteers. The procedure of bioequivalence between the test product (Amplium® - FARMASA) and reference product (Pletil® - Pharmacia do Brasil Ltda) was a randomized, crossover and open study. The medication was administered in a single dose of 500 mg of tinidazole to 24 healthy volunteers. Blood samples were collected until 72 hours after administration and analised using a validated high-performance liquid chromatographic method with UV detection. The average plasmatic decay curves obtained for the test product (Amplium® - FARMASA) and reference product (Pletil® - Pharmacia do Brasil Ltda) were similar, in the same way as were the pharmacokinetic parameters Cmax (reference: 11.34 µg/mL; test: 11.11 µg/mL), tmax (reference: 1.67 h; test: 1.71 h), AUC0-t (reference: 201.92 µgxh/mL; test: 198.15 µgxh/mL), AUC0-&#8734; (reference: 208.25 µg/mL; test: 203.80 µgxh/mL) and t(½)el (reference = 14.05 hours, test = 13.91 hours). The multivariate analysis accomplished through analysis of variance (ANOVA), for assessment of product, group and period effects, revealed the absence of any of these effects in the present study, indicating that the crossover design was properly performed. j The 90% confidence intervals for the ratio of Cmax (93.9 % - 102.6 %), AUC0-t (94.9 % - 101.1 %) and AUC0-&#8734; (94.6 % - 100.8 %) values for the test and reference products are within the 80 - 125 % interval proposed by FDA and ANVISA. Statistical comparison of AUC0-t , AUC0-&#8734; and Cmax clearly indicated no significant difference between the two brands of tinidazole 500 mg tablets. Based on the pharmacokinetic and statistical results of this study, we can conclude that the two products are bioequivalent, and can be considered interchangeable in medical practice

Cohort migration of carcinoma cells: Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets

Active migration of tumor cells is usually assessed as single cell locomotion in vitro using Royden chamber-type assays. In vivo, however, carcinoma cells, malignant cells of epithelial origin, frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration". In our work, the invasion front of colon carcinomas consisted of compact tumor glands, partially resolved glands or markedly resolved glands with scattered tumor cell clusters or single cells lying ahead. In the former two types, which constituted about a half of all cases, cohort migration seems to be the predominant mechanism, whereas both cohort migration and single cell locomotion may be involved in the last one. In this light, it is very advantageous to investigate the mechanisms involved in the cohort migration. In this review, we present a two-dimensional motility assay as a cohort migration model, in which human colorectal carcinoma cells move outwards from the cell islands mainly as localized coherent sheets of cells when stimulated with 12-0-tetradecanoylphorbol- 13-acetate (TPA) or hepatocyte growth factorlscatter factor (HGFISF). Within the migrating cell sheets, wide intercellular gaps occur at the lower portion of the cells to allow the cells to extend leading lamellae forward while close cell-cell contacts remain at the upper portion of the cells. This localized modulation of cell-cell adhesion at the lower portion of the cells is associated with increased tyrosine phosphorylation of the Ecadherin- catenin complex in TPA-induced cohort migration and with reduced α-catenin complexed with E-cadherin in HGFISF-induced cohort migration. Furthermore, fibronectin deposited by migrating cells is essential for their movement, and on the gelatin-coated substrate even degradation and remodeling of the substrate by matrix metalloproteinases are also needed. Thus, in cohort migration it is likely that cells are released from cell-cell adhesion only at the lower portion of the cells via modulation of E-cadherin-catenin-based mechanism, and this change allows the cells to extend leading lamellae onto the extracellular matrix substrate remodeled by deposition of fibronectin and organized digestion

Bioequivalence evaluation of tinidazole 500 mg tablets

Tinidazol, 1-[2-(ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole, é um membro da classe dos nitroimidazóis que apresenta atividade amebicida, giardicida, tricomonicida e anaeróbica. O objetivo deste estudo foi avaliar a bioequivalência de duas marcas comerciais de comprimidos contendo 500 mg de tinidazol em voluntários sadios. O ensaio de bioequivalência entre o produto teste (Amplium® - FARMASA) e o produto referência (Pletil® - Pharmacia do Brasil Ltda) foi do tipo randomizado, cruzado e aberto. O medicamento foi administrado em dose única de 500 mg de tinidazol a 24 voluntários sadios. Amostras de sangue foram coletadas até 72 horas após a administração e analisadas através de método de cromatografia líquida de alta eficiência validado com detecção UV. As curvas médias de decaimento plasmatico obtidas para o produto teste (Amplium® - FARMASA) e para o produto referência (Pletil® - Pharmacia do Brasil Ltda) foram semelhantes, da mesma forma que os parâmetros farmacocinéticos Cmax (referência: 11,34 µg/mL; teste: 11,11 µg/mL), t<SUB.max (referência: 1,67 h; teste: 1,71 h), AUC0-t (referência: 201,92 µgxh/mL; teste: 198,15 µgxh/mL), AUC0-&#8734; (referência: 208,25 µg/mL; teste: 203,80 µgxh/mL) e t(½)el (referência = 14,05 h; teste = 13,91 h). A análise multivariada realizada através da análise de variância (ANOVA), para avaliação dos efeitos produto, grupo e período, revelou a ausência destes efeitos no estudo, indicando que o delineamento do estudo foi apropriado. Os valores do intervalo de confiança 90% para a razão de Cmax (93.9 % - 102.6 %), AUC0-t (94.9 % - 101.1 %) e AUC0-&#8734; (94.6 % -100.8 %) encontram-se entre 80 - 125 %, intervalo proposto pelo FDA e ANVISA. A comparação estatística dos parâmetros AUCo-t , AUC0-&#8734; e Cmax indicam claramente não haver diferença significativa entre os dois produtos contendo 500 mg de tinidazol. Baseado nos resultados farmacocinéticos e estatísticos deste, pode-se concluir que os dois produtos são bioequivalentes e podem ser considerados intercambiáveis na terapêutica.Tinidazole, 1-[2-(ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole, is a member of the 5-nitroimidazole class of antimicrobial agents with amoebicidal, giardicidal, trichomonicidal and anaerobic activity. The purpose of this study was to evaluate the bioequivalence of two brands of tinidazole 500mg tablets in healthy human volunteers. The procedure of bioequivalence between the test product (Amplium® - FARMASA) and reference product (Pletil® - Pharmacia do Brasil Ltda) was a randomized, crossover and open study. The medication was administered in a single dose of 500 mg of tinidazole to 24 healthy volunteers. Blood samples were collected until 72 hours after administration and analised using a validated high-performance liquid chromatographic method with UV detection. The average plasmatic decay curves obtained for the test product (Amplium® - FARMASA) and reference product (Pletil® - Pharmacia do Brasil Ltda) were similar, in the same way as were the pharmacokinetic parameters Cmax (reference: 11.34 µg/mL; test: 11.11 µg/mL), tmax (reference: 1.67 h; test: 1.71 h), AUC0-t (reference: 201.92 µgxh/mL; test: 198.15 µgxh/mL), AUC0-&#8734; (reference: 208.25 µg/mL; test: 203.80 µgxh/mL) and t(½)el (reference = 14.05 hours, test = 13.91 hours). The multivariate analysis accomplished through analysis of variance (ANOVA), for assessment of product, group and period effects, revealed the absence of any of these effects in the present study, indicating that the crossover design was properly performed. j The 90% confidence intervals for the ratio of Cmax (93.9 % - 102.6 %), AUC0-t (94.9 % - 101.1 %) and AUC0-&#8734; (94.6 % - 100.8 %) values for the test and reference products are within the 80 - 125 % interval proposed by FDA and ANVISA. Statistical comparison of AUC0-t , AUC0-&#8734; and Cmax clearly indicated no significant difference between the two brands of tinidazole 500 mg tablets. Based on the pharmacokinetic and statistical results of this study, we can conclude that the two products are bioequivalent, and can be considered interchangeable in medical practice

Ex-W-Pert System: A Web-Based Distributed Expert System for Groupware Design

The World Wide Web (Web) allows people at remotely located sites to communicate and share their ideas using a common communication protocol. A common use of the Web system is running a client application, using a browsing tool, by pointing to a local or proxy server to browse data written in the hypertext format that contains anchors that address other URLs. In this paper a new application of the Web system for sharing knowledge based systems and groupware development activities is introduced. An architecture for a Web-based Distributed Expert System (Ex-W-Pert System) is proposed and an implementation of the proposed architecture in groupware design is demonstrated. The resources and knowledge bases are distributed and can be accessed through the internet. Keywords: World Wide Web (WWW), Expert System, Communication Engine, Groupware System, Design 1 INTRODUCTION The World Wide Web (Web) allows people at remotely located sites to communicate and share their ideas using a c..