Determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil using surface plasmon resonance band of silver nanoparticles

The aim of this work is to evaluate simple, sensitive, effective and validated procedures for the determination of cefotaxime, cefoperazone, ceftazidime and cefadroxil. In this study, the methods based on the ability of the cited drugs to reduce Ag+ ions to silver nanoparticles (Ag-NPs) in the presence of Polyvinyl Pyrrolidone (PVP) as a stabilizing agent producing very intense surface plasmon resonance peak of Ag-NPs (λmax. = 410-430 nm). The plasmon absorbance of the Ag-NPs allows the quantitative spectrophotometric determination of the cited drugs. The calibration curves are linear with concentration ranges of 0.4-3.2, 1-8, 0.5-4.0 and 1.5-9.0 µg/mL for cefotaxime, cefoperazone, ceftazidime and cefadroxil, respectively. Apparent molar absorptivity, detection and quantitative limits are calculated. Applications of the proposed methods to representative pharmaceutical formulations are successfully presented. The extracellular synthesis of nanoparticles is fast, and the method doesn't require various elaborate treatments and tedious extraction procedures.

Estudio de susceptibilidad a cefalosporinas de primera generación en enterobacterias aisladas de urocultivo, según criterios CLSI y EUCAST / Susceptibility to first-generation Cephalosporins in Enterobacteriaceae isolated from urine culture according to CLSI and EUCAST breakpoints

Resumen Actualmente se recomienda el uso de cefazolina para determinar la susceptibilidad a cefalosporinas orales de primera generación en cepas de enterobacterias en ITU no complicada. Nuestro objetivo fue establecer la susceptibilidad a cefalosporinas orales en cepas urinarias según puntos de corte para cefalotina o cefazolina y la correlación de susceptibilidad entre cefazolina y cefadroxilo. Se estudió la concordancia entre cefalotina y cefazolina en 52 cepas por método de Kirby-Bauer y Vitek XL. En Escherichia coli fue de 0% para VitekXL y 50% para Kirby-Bauer. La concordancia entre cefazolina y cefadroxilo fue 95,6%. En el laboratorio debiera usarse cefazolina para determinar susceptibilidad a cefalosporinas orales de primera generación. La concordancia entre cefazolina y cefadroxilo sugiere que cefazolina podría predecir susceptibilidad para cefadroxilo.

Currently, the use of cefazolin is recommended to determine the susceptibility to first-generation oral cephalosporins in strains of enterobacteria in uncomplicated UTI. We determined susceptibility differences to oral cephalosporins in urinary strains according to cefazolin or cefalotin breakpoints and the correlation of susceptibility between cefazolin and cefadroxil. We studied 52 strains with cefalotin and cefazolin by disk-diffusion and MIC (Kirby-Bauer and Vitek XL) and a subgroup by disk-diffusion for cefadroxil. Agreement among different methods was 100% for K. pneumoniae and Proteus spp. In Escherichia coli, agreement for Vitek and disk-diffusion were 0 and 50% respectively. Susceptibility to first generation cephalosporins in E. coli should be determined with cefazolin. Agreement between cefazolin and cefadroxil suggests that cefazolin could also predict the susceptibility of cefadroxil.

Evaluation of the effect of topical cefadroxil on bacterial load of pathogenic staphylococci in anterior nares in human volunteers, comparative study between oral vs. topical cefadroxil.

Background: Cefadroxil has good tissue penetration & exerts more sustained action at the site of infection after oral absorption. Our aim of the study was to check topical cefadroxil has any efficacy over staphylococcal superficial skin infection or not. Methods: Pre-treatment nasal swabs were obtained from 25 healthy human volunteers and bacterial load was recorded. After single application of topical cefadroxil 3% in left anterior nare and placebo (vehicle) in right anterior nare nasal swabs were obtained and results were compared. 150 patients with staphylococcal superficial skin infections were distributed in 4 groups: Group A - oral cefadroxil 500 mg twice daily for 5 days, Group B - topical cefadroxil (0.5 % to 5%) twice daily, Group C - cefadroxil 500 mg orally plus placebo (vehicle) topically twice daily and Group D -cefadroxil 500 mg orally plus cefadroxil preparation topically twice daily. Bacterial load was measured before treatment, on follow up &after clinical cure and results were compared. Results: Topical cefadroxil significantly reduced bacterial load after single application in anterior nare. Topical cefadroxil cured and significantly reduced bacterial load in staphylococcal superficial skin infections within 3 days of treatment. Oral plus topical cefadroxil combination therapy significantly reduced bacterial load and cured infection within 3 days of treatment in patients with moderate to heavy bacterial growth. No any adverse effect was observed during entire study period in any of groups. Conclusions: Topical preparation of cefadroxil is safe and effective in treating staphylococcal superficial skin infections. Combination of oral plus topical cefadroxil showed synergistic effect in infections with moderate to heavy growth. This study is registered at CTRI [REG ID: CTRI/2013/02/003433 REF: REF/2013/02/004576].

Cefadroxil potency as cancer co-therapy candidate by glutathione s-transferase mechanism

Background: Glutathione S-transferases (GSTs) have an important role in the detoxification of electrophiles, such as some anticancer drugs. Compounds with phenolic and/or α,b-unsaturated carbonyl group have been known as GSTs inhibitor in vitro. Cefadroxil in vitro decreased GST-Pi activity but not GSTs in rat kidney cytosol. GST inhibitor in a specific organ and of a specific class is needed for safety in cancer chemotherapy. The study aims to observe the effect of cefadroxil on GSTs in vivo in rat kidney cytosol and then compare it to those seen for liver, lung, and spleen in vivo. Methods: Cefadroxil was given twice a day by forcefeeding for five days. Rat kidney cytosol was then prepared and its protein concentration was determined. Cytosolic total GST, GST-Mu and GST-Pi activities were monitored by a continuous spectrophotometric method using the following substrates: 1-chloro, 2,4-dinitrobenzene (CDNB) (non-specific substrate), 1,2-dichloro-4-nitrobenzene (DCNB) for GST-Mu, and ethacrynic acid (EA) for GST-Pi. Results: The data showed that cefadroxil significantly increased the activity of GSTs, GST-Mu, and GSTPi in rat kidney cytosol (8.75%, 47.81%, and 6.67% respectively). Conclusion: Cefadroxil did not inhibit GSTs, GST-Mu, and GST-Pi in rat kidney in vivo indicating that it does not inhibit chemotherapy detoxification by GSTs, GSTMu, and GST-Pi in normal kidney cells.

Profilaxis antimicrobiana en cirugía ortopédica: cefazolina vs cefadroxilo IV / Antimicrobial prophylaxis in orthopedic surgery: cefazolina vs cefadroxilo IV

Toda intervención quirúrgica está expuesta a infectarse. La necesidad de profilaxis antimicrobiana en cirugía ortopédica para casos quirúrgicos agudos o electivas de cirugías limpias ha sido establecida como procedimiento de rutina. En Cirugía Ortopédica y Traumatología cuando se requiere el uso de implantes metálicos con el fin de realizar osteosíntesis o sustitución de las superficies articulares, aumenta el riesgo de infección, por tratarse de materiales extraños que son introducidos en el organismo. En estos casos la antibióticoterapia preventiva es de primordial importancia. Se realizó un estudio de profilaxis antimicrobiana, multicéntrico, aleatorizado, prospectivo, doble ciego, comparativo de grupos paralelos, con el fin de evaluar la eficacia de Cefadroxilo I.V. Vs. Cefazolina I.V. como antibióticos profilácticos mediante la determinación del número de pacientes infectados en cirugía de fracturas cerradas en la cuales se colocó material de síntesis. Se completaron 58 pacientes, 34 en el grupo de cefadroxilo y 24 en el grupo de cefazolina, al inicio los grupos fueron similares en cuanto a edad, sexo, tipo de fractura, tiempo de intervención, tiempo entre la fractura y la intervención.Más pacientes en el grupo de cefadroxilo tenían el tiempo máximo autorizado entre la fractura y la intervención (p: 0,07). Se presentó en el grupo de cefadroxilo una infección de la herida operatoria y un caso de eritema leve que cedió con tratamiento oral con cefadroxilo, sin diferencias entre los grupos.Hubo tres casos de eventos adversos, reacción anafiláctica a las 48 horas en el grupo de cefazolina que ameritó finalización de protocolo y hematoma en miembro inferior derecho y, en el grupo de cefadroxilo, una elevación discreta de enzimas hepáticas. La respuesta terapéutica de profilaxis antimicrobianano mostró diferencia entre los grupos. El cefadroxilo es tan eficaz como la cefazolina para la profilaxis antimicrobiana en pacientes con fracturas...

Any operation is exposed to infection. The need for antimicrobial prophylaxis in orthopedic surgery for acute or elective surgical cases of clean surgery is established as a routine procedure. Orthopedic Surgery when required the use of metallic implants in order to perform internal fixation or replacement of the articular surfaces, increases the risk of infection because they are foreign materials are introduced into the body. In these cases, preventive antibiotic therapy is very important. We performed a study of antimicrobialprophylaxis multicenter, randomized, prospective, double-blind, parallel group comparison in order to evaluate the effectiveness of Cefadroxil IV vs. Cefazolin I.V. as prophylactic antibiotics by determining the number of infected patients after fracture surgery in which synthetic material was placed. Fifty eigth patients were completed, 34 in the cefadroxil group and 24 in the cefazolin group, at the beginning the groups were similar in age, sex, fracture type, operative time, time between fracture and surgery. More patients in the cefadroxil group had the maximum allo-wable time between the fracture and surgery. (P: 0.07). In the cefadroxil group we found a wound infection and one case of mild erythema which resolved with oral treatment with cefadroxil, without differences between groups. There were three cases of adverse events, anaphylactic reaction to cefazolin at 48 h in the group that required finalization of protocol and hematoma in right leg and in the cefadroxil group, a moderate increase in liver enzymes. The therapeutic response of antimicrobial prophylaxis showed no difference between groups. Cefadroxil is as effective as cefazolin for antimicrobial prophylaxis in patients with fractures that warrant placement of synthetic material

Avaliação de diferentes cronogramas de coletas de amostras biológicas em estudos de bioequivalência e análise da influência de teor de fármaco sobre os resultados destes estudos / Evaluation of the effects on different doses and sampling schedules on the assessment of bioequivalence

Os estudos de bioequivalência são realizados em humanos, por meio da administração dos medicamentos em estudo pela mesma via extravascular, sob condições experimentais padronizadas, seguida pela determinação das concentrações plasmáticas do fármaco em função do tempo. Nestes estudos considera-se que curvas estatisticamente semelhantes de decaimento sanguíneo de fármacos produzem o mesmo resultado em termos de eficácia e segurança. A partir das curvas de concentração em função do tempo obtidas, determinam-se os parâmetros farmacocinéticos Cmax, tmax e ASC. A bioequivalência entre dois produtos é estabelecida por meio do IC 90%, que deve estar entre 80 a 125% para os parâmetros farmacocinéticos Cmax e ASC. O cronograma de coleta de amostras biológicas é um dos aspectos mais críticos no planejamento de estudos de bioequivalência, pois este afeta diretamente a determinação dos parâmetros farmacocinéticos utilizados na avaliação da bioequivalência. Outro aspecto importante relacionado a este tipo de estudo é a diferença de teor entre os produtos a serem submetidos ao estudo de bioequivalência, que segundo a legislação brasileira vigente, deve ser menor ou igual a 5%. Neste trabalho foram avaliados diferentes cronogramas de coleta de amostras sangue, avaliando-se o impacto destes no resultado final de um estudo de bioequivalência e, além disso, a influência da diferença de teor de fármaco entre dois produtos que levaria à bioinequivalência também foi investigada. Para tanto simulações matemáticas e um estudo in vivo foram conduzidos. O fármaco modelo escolhido foi a cefadroxila, por apresentar características farmacocinéticas e farmacodinâmicas ideais. O programa Microsoft Office Excel 2003 foi utilizado para simular as concentrações plasmáticas e determinar o IC 90%. As simulações foram feitas por meio de dois modelos: modelo baseado em máximos e mínimos de parâmetros farmacocinéticos, e modelo baseado em coeficientes de variação intra e inter-individuais do fármaco. Dez diferentes doses, entre -10% a 20% da dose referência, e 6 cronogramas de coleta foram avaliados. O estudo in vivo foi realizado com quatro doses diferentes de cefadroxila. A bioequivalência entre as doses e em diferentes cronogramas de coleta foi avaliada em 24 voluntários sadios do sexo masculino. Os voluntários receberam as quatro doses do estudo em desenho cruzado, em quatro períodos e quatro seqüências, com washout de 7 dias entre as doses. As concentrações plasmáticas de cefadroxila, até 8 horas após a administração, foram determinadas por cromatografia líquida de alta eficiência com detecção DAD. Os parâmetros farmacocinéticos tmax, Cmax e AUC0-t foram determinados nas diferentes doses e cronogramas de coleta, sendo que o critério para estabelecer-se a bioequivalência foi baseada nos resultados do IC 90% dos parâmetros farmacocinéticos Cmax e AUC0-t. Os resultados obtidos nas simulações mostraram boa correlação com os dados reais obtidos a partir de estudos in vivo. As simulações baseadas em coeficientes de variação intra e inter-individuais descreveram melhor os resultados observados no estudo in vivo. De acordo com os resultados obtidos no estudo in vivo pode-se concluir que cronogramas de coletas com menos amostras são tão eficientes quanto cronogramas de coletas com mais amostras, desde que o tempo de tmax esteja incluído. Em relação ao teor de fármaco, concluiu-se que dois produtos com diferença de teor menor ou igual a 11% ainda são bioequivalentes e que diferença maior ou igual a 14% resultam em bioinequivalência. Observou-se ainda que o parâmetro farmacocinético ASC0-t é mais sensível que Cmax para detectar diferenças

Bioequivalence studies are designed to compare the in vivo performance of different formulations of the same drug or different drug products by a randomized crossover study. Pharmacokinetic parameters are obtained from the drug concentration-time profile in blood, serum, or plasma. The most frequently used pharmacokinetic parameters are area under the plasma or blood concentration-time curve (AUC), maximum concentration (Cmax) and time to achieve maximum concentration (tmax). Bioequivalence is concluded if the average bioavailability of the test formulation is within (80%, 125%) that of the reference formulation, with a certain assurance, that is, an equivalence criterion of 80% to 125% for assessment of bioequivalence based on the ratio of average bioavailability is employed. The logarithmic transformation is used for AUC and Cmax. Accuracy in measuring pharmacokinetics parameters directly affects accuracy of bioequivalence tests. Since the number of blood samples per patient is limited, sampling points should be chosen such that the time concentration profile is adequately defined so as to allow the calculation of relevant parameters. According to guidelines proposed by the National Agency of Sanitary Vigilance of Brazil (ANVISA), bioequivalence studies can be conducted only if the difference in drug content between the reference and test product is less than or equal to 5%. The goals of this study are to evaluate the influence of differences in amount of active moiety present in the formulation and possibility of reducing the number of sampling points in bioequivalence studies and to discuss the impact of these parameters in bioequivalence conclusions. For these approaches, simulations and an in vivo study were done. The drug selected was cefadroxil. Cefadroxil presents ideal pharmacokinetics and pharmacodynamics characteristics for this kind of study, such as high bioavailability, low intra and intersubject variability, short elimination rate and wide therapeutic range. Microsoft Office Excel 2003 software was used to simulate drug concentration-time profiles for different doses and several sampling schedules, and to determine 90% confidence interval. Simulations were done by two models: a) based on assumed maximum and minimum pharmacokinetic parameters values; b) based on assumed intra and intersubject variability. Ten different doses, ranging from -10% to 20% of the reference dose, and six sampling schedules were evaluated. The in vivo study was performed with four different cefadroxil doses. Their relative bioavailability were evaluated in 24 healthy volunteers who received a single oral dose of each preparation. An open, randomized clinical trial designed as four-periods and four sequences crossover with 7-days washout between doses was employed. Plasma samples for assessments of their cefadroxil concentration by HPLC-DAD were obtained over 8 h after administration. Pharmacokinetics parameters tmax, Cmax and AUC0-t were evaluated using different doses and sampling schedules. For the purpose of bioequivalence analysis Cmax and AUC0-t were considered. For each schedule, to claim bioequivalence in average bioavailability, a 90% confidence interval was constructed for ratio of average between test and reference products and compared with (80%, 125%) limits. If the constructed confidence interval falls within the limits, then the two formulations are considered bioequivalent. The results obtained by simulate time-concentration profiles, showed good correlation with real data. Comparing the results obtained through in vivo study and the two simulations models, the simulations based in intra and intersubject variability was more predictive. In conclusion, no significant differences were found between sampling schedules evaluated, since the sampling time around tmax were maintained in sampling schedules. Bioinequivalence was observed when the difference between cefadroxil doses was higher than 14%. The parameter AUC0-t was more sensitive than Cmax to detect differences

Study on Dissolution of Cefadroxil Tablets and Cefadroxil Capsules from Different Manufactures / 中国药房

OBJECTIVE:To compare the dissolution rates of cefadroxil preparations from A,B and C3manufacturers and to provide references for rational clinical drug use.METHODS:The contents were determined by UV-spectrophotometry with the detection wavelength at263nm;The dissolution was determined by oar method with water as the solvent and with rotation speed at50r/min,the stripping curves were drawn,the parameters of T d ,m and?were figured out,and on which ANOVA was conducted;Besides,the dissolution tests were conducted on cefadroxil capsules that from manufacturer C by oar method and baskets-rotating methods simultaneously and the results of which were subjected to t-tests.RESULTS:The values of T d and?of cefadroxil capsules and cefadroxil tablets had significant differences(P0.05),but sig?nificances were found in m value between2batches of cefadroxil tables;The dissolution values of2batches of capsules from manufacturer C were signficances determined by oar method and rotation basket method respectively for less than10min and20min(P

A Simple and Sensitive Assay for Cefepime in Human Plasma Using High Performance Liquid Chromatography

A simple and sensitive assay method was developed for cefepime in human plasma using high performance liquid chromatography (HPLC). Cefepime and cefadroxil (the internal standard) were extracted from heparinized human plasma by simple deproteination with perchloric acid. The extract was injected into an Atlantis dC18 column (250 X 4.6 mm; particle size 5micrometer, Waters) and the column was eluted with methanol and 0.01 M dihydrogen phosphate at pH 3.0 (15 : 85 v : v) as a mobile phase at a flow rate of 0.7 mL/min. Linearity was confirmed for the range 0.25 to 200 micro L/mL and the limit of quantitation was 0.25 micro L/mL. The retention times were 10.2 min and 13.4 min for cefepime and cefadroxil, respectively. This method was successfully applied to a pharmacokinetic study of cefepime in plasma from bone marrow transplant patients.

A case of bronchial asthma due to cefadroxil in a housewife / 천식및알레르기

Cephalosporins are the most important -lactams that induce IgE-mediated reactions. Also, cephalosporins have been known as a causative agent for occupational asthma in pharmaceutical workers. To our knowledge, this is the first report of cephalosporin-induced bronchial asthma in a housewife with no history of occupational exposure. We experienced a 30-year old female who had developed shortness of breath, coughing and itching sensation of the skin since 3 years ago whenever she handled drug powder for upper respiratory infections (URI) prescribed for her two sons with bronchial asthma. She had handled drug powder for 7 years because her sons had experienced frequent URI. Skin prick test with cefadroxil (10mg/ml) and cefaclor (10mg/ml) showed positive reactions. Bronchial challenge test with cefadroxil showed immediate asthmatic reaction, and bronchial challenge with cefaclor showed immediate urticaria and angioedema without significant fall in FEV1. We confirmed cefadroxil-induced bronchial asthma sensitized by intermittent inhalation in a non-occupational setting.

Study on Pharmacokinetics and Bioequivalence of Two Products of Cefadroxil Capsules in Healthy Volunteers / 中国药房

OBJECTIVE:To study the bioequivalence between cefadroxil capsules and its reference capsules and pharmacokinetics in 22 male healthy volunteers METHODS:A dose of 1 000mg cefadroxil(test and reference products)was given according to a randomized cross-over design Plasma concentrations of cefadroxil and internal standard(amoxicillin) were determined by HPLC RESULTS:The concentration-time curves of both preparations fitted to a one-compartment model The main parameters of test and reference products were as follows:T1/2ke were (1 40?0 15)h and (1 44?0 23)h;Tmax were (2 3?0 5)h and (2 2?0 3)h;peak concentrations(Cmax) were (30 59?4 25)?g/ml and(30 57?4 24)?g/ml,AUC were(99 31?14 50)?g/(ml?h) and (99 22?15 11)?g/(ml?h)respectively CONCLUSION:Relative bioavailability was(100 42?7 62)% The two formulations were bioequivalent

Efficacy of Cefadroxil Monohydrate (Duricef / 대한비뇨기과학회지

Effect of Cefadroxil monohydrate was evaluated on 37 patients with urinary tract infection in our department during past 6 months periods. Cefadroxil was given Orally at a dose of 1.0 gm - 3.0 gm bid per day for 3 - 15 days and following results were obtained. 1. Excellent or good results was observed in 31 out of 34 patients in whom complete follow up study were done, giving success rate of 91.2%. 2. Therapeutic effects were obtained in 10 out of 11 patients with urethritis and all patients with cystitis and pyelonephritis, but not in 1 with urethritis, 1 with prostatitis and 1 out of 9 urinary tract infections with predisposing factors. 3. In this clinical settings, Cefadroxil was effective against E. coli infection in 10 patients, mixed infection in 2 and Staphylococcus aureus infection in 5. However it was ineffective against Serratia infection in 1 patient and Staphylococcus infection in 1. 4. As to the side effects, only mild dizziness was observed in 2 patient.