Multicomponent kinetic spectrophotometric determination of pefloxacin and norfloxacin in pharmaceutical preparations and human plasma samples with the aid of chemometrics

A spectrophotometric method for the simultaneous determination of the important pharmaceuticals, pefloxacin and its structurally similar metabolite, norfloxacin, is described for the first time. The analysis is based on the monitoring of a kinetic spectrophotometric reaction of the two analytes with potassium permanganate as the oxidant. The measurement of the reaction process followed the absorbance decrease of potassium permanganate at 526 nm, and the accompanying increase of the product, potassium manganate, at 608 nm. It was essential to use multivariate calibrations to overcome severe spectral overlaps and similarities in reaction kinetics. Calibration curves for the individual analytes showed linear relationships over the concentration ranges of 1.0–11.5 mg L−1 at 526 and 608 nm for pefloxacin, and 0.15–1.8 mg L−1 at 526 and 608 nm for norfloxacin. Various multivariate calibration models were applied, at the two analytical wavelengths, for the simultaneous prediction of the two analytes including classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), radial basis function-artificial neural network (RBF-ANN) and principal component-radial basis function-artificial neural network (PC-RBF-ANN). PLS and PC-RBF-ANN calibrations with the data collected at 526 nm, were the preferred methods—%RPET not, vert, similar 5, and LODs for pefloxacin and norfloxacin of 0.36 and 0.06 mg L−1, respectively. Then, the proposed method was applied successfully for the simultaneous determination of pefloxacin and norfloxacin present in pharmaceutical and human plasma samples. The results compared well with those from the alternative analysis by HPLC.

Pefloxacin therapy for experimental endocarditis caused by methicillin-susceptible or methicillin-resistant strains of Staphylococcus aureus

The therapeutic efficacy of pefloxacin in experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus was evaluated. In rabbits infected with a methicillin-susceptible strain, 4 days of pefloxacin therapy significantly reduced both the number of bacteria per gram of vegetation and the mortality rate compared with untreated controls, and pefloxacin was equivalent to cephalothin. Pefloxacin was also as effective as vancomycin in reducing vegetation titers and mortality rate in animals with endocarditis caused by a methicillin-resistant strain. These results suggest that pefloxacin may be an effective agent in the therapy of serious infections caused by either methicillin-susceptible or -resistant strains of S. aureus.

Fabrication of Electrochemical Sensors for Pharmaceutical Analysis

Potentiometric chemical sensors,an important class of electro-chemical sensors are widely used in pharmaceutical analysis because of its inherent advantages.The present study was aimed at fabrication of potentiometric sensors for the drugs mebendazole,pefloxacin,ambroxol,sildenafil citrate,dextro-methorphan and tetracycline.A total of 18 sensors have been developed for the determination of theses drugs.The major step in the fabrication of the sensor was the preparation of the ion association.Two types of sensors viz:PVC membrane sensor and carbon paste electode (CPE) were fabricated.The response characteristics of the different sensors fabricated were studied.Various response parameters studied include response time,selectivity and the effect of pH.The developed sensors were also employed for the determination of the drugs in pharmaceutical formulations and also for the recovery of the drug from urine samples.The selectivity studies reveal that the developed sensors are highly selective to the drug even in prescence of foreign ions.

Estudo sobre a resistencia aos antimicrobianos em bacterias isoladas de pacientes hospitalizados (Botucatu, 1988-1992)

Since 1988 to 1992, a study about susceptibility to antimicrobial drugs of bacterias isolated from hospitalized patients was performed. The compared susceptibility to important drugs (ampicillin, cephalotin, cefoxitin, ceftaxizime, ceftriaxone, aztreonam, gentamicin, amikacin, pefloxacin, ciprofloxacin, imipenem, oxacillin and vancomycin) was investigated in 1200 strains (300 of each specie) of the prevalent bacterias: E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and S. aureus. Minimal inhibitory concentration (MIC) was determined by agar dilution method, using from 0.05 to 256 mcg of each drug per ml of culture medium (Mueller-Hinton). Ranges of MIC, MIC(50%), MIC(90%) and the proportion of resistant strains were determined and permitted to know the 4 drugs that were found to be more active against bacterias; the CIM(90%) values are: E. coli - aztreonam (0.1 mcg/ml), pefloxacin (0.1), ceftazidime (0.25) and ceftriaxone (0.05); K. pneumoniae-aztreonam (0.25) ceftriaxone (0.25), ceftazidime (0.5) and pefloxacin (2.0); P. aeruginosa-imipenem (4.0), aztreonam (16), ceftazidime (16) and ciprofloxacin (16); S. aureus-vancomycin (1.01, ciprofloxacin (8, 0), amikacin (128) and cephalothin (128 mg/ml). The better 'in vitro' antibacterial activity observed was related to: aztreonam (77-100% of the sensitive strains), ceftazidime (50-99,7%), pefloxacin (73-99,7%), ciprofloxacin (80%), imipenem (93%) and vancomycin (100%).

Estudo sobre a resistência aos antimicrobianos em bactérias isoladas de pacientes hospitalizados (Botucatu, 1988-1992)

Since 1988 to 1992, a study about susceptibility to antimicrobial drugs of bacterias isolated from hospitalized patients was performed. The compared susceptibility to important drugs (ampicilin, cephalothin, cefoxitin, ceftazidime, ceftriaxone, aztreonam, gentamicin, amikacin, peftoxacin, ciprofloxacin, imipenem, oxacillin and vancomicin) was investigated in 1200 strains (300 of each specie) of the prevalent bacterias: E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and S. aureus. Minimal inhibitory concentration (MIC) was determined by agar dilution method, using from 0,05 to 256 mcg of each drug per ml of culture medium (Mueller-Hinton). Ranges of MIC, MIC 50%, MIC 90% and the proportion of resistant strains were determined and permited to know the 4 drugs that were found to be more active against bacterias; the CIM 90% values are: E. coli - aztreonam (0,1 mcg/ml), pefloxacin (0,1), ceftazidime (0,25) and ceftriaxone (0,05); K. pneumoniae - aztreonam (0,25), ceftriaxone (0,25), ceftazidime (0,5) and pefloxacin (2,0); P. aeruginosa - imipenem (4,0), aztreonam (16), ceftazidime (16) and ciprofloxacin (16); S. aureus - vancomicina (1,0), ciprofloxacin (8,0), arnicacina (128) and cephalothin (128 mg/ml). The better in vitro antibacterial activity observed was related to: aztreonam (77-100% of the sensitive strains), ceftazidime (50-99,7%), pefloxacin (73-99,7%), ciprofloxacin(80%), imipenem (93%) and vancomicin (100%).

Esparfloxacino e as fluorquinolonas: Uma revisao de sua classificacao, atividade antibacteriana, mecanismo de acao, caracteristicas farmacocineticas, tolerabilidade e perspectivas farmaceuticas

A revision was accomplished in the literature on the quinolones, antibacterial class that presents wide action spectrum, focusing, mainly, the sparfloxacin, third generation fluorquinolone which has potente activity against Gram positive organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA), Gram negative organisms, Legionelia spp, Mycoplasma spp, Chlamydia spp and Mycobacterium spp, including multidrug resistant organisms.

Efeito do substituinte “-F” nas propriedades electrónicas e estruturais de fluoroquinolonas

Este estudo incide sobre as características que a presença do ião flúor em moléculas concede. Mais concretamente em fluoroquinolonas, antibióticos que cada vez são mais utilizados. Fez-se uma analise de vários parâmetros para obtermos informação sobre a interação fármaco-receptor nas fluoroquinolonas. Sendo para isso utilizadas técnicas de caracterização química computacional para conseguirmos caracterizar eletronicamente e estruturalmente (3D) as fluoroquinolonas em complemento aos métodos semi-empíricos utilizados inicialmente. Como é sabido, a especificidade e a afinidade para o sitio alvo, é essencial para eficácia de um fármaco. As fluoroquinolonas sofreram um grande desenvolvimento desde a primeira quinolona sintetizada em 1958, sendo que desde ai foram sintetizadas inúmeros derivados da mesma. Este facto deve-se a serem facilmente manipuladas, derivando fármacos altamente potentes, espectro alargado, factores farmacocinéticos optimizados e efeitos adversos reduzidos. A grande alteração farmacológica para o aumento do interesse neste grupo, foi a substituição em C6 de um átomo de flúor em vez de um de hidrogénio. Para obtermos as informações sobre a influência do ião flúor sobre as propriedades estruturais e electrónicas das fluoroquinolonas, foi feita uma comparação entre a fluoroquinolona com flúor em C6 e com hidrogénio em C6. As quatro fluoroquinolonas presentes neste estudo foram: ciprofloxacina, moxiflocacina, sparfloxacina e pefloxacina. As informações foram obtidas por programas informáticos de mecânica quântica e molecular. Concluiu-se que a presença de substituinte flúor não modificava de forma significativa a geometria das moléculas mas sim a distribuição da carga no carbono vicinal e nos átomos em posição alfa, beta e gama relativamente a este. Esta modificação da distribuição electrónica pode condicionar a ligação do fármaco ao receptor, modificando a sua actividade farmacológica.