Efficacy of secnidazole-diminazene aceturate combination therapy in the late treatment of Trypanosoma brucei brucei infection in dogs

This study evaluated the efficacy of combination therapy of secnidazole-diminazene aceturate (SEC-DA) in late treatment of dogs experimentally infected with relapsing strain of Trypanosoma brucei brucei. Fifteen dogs were randomly assigned to 5 groups (A - E) of 3 per group. Group A (uninfected untreated), B (infected untreated), C (infected and treated with DA (3.5 mg/kg) IM stat), D (infected and treated with secnidazole (SEC) (100 mg/kg) orally for 5 days and DA (3.5 mg/kg) IM stat), E (infected and treated with SEC (200 mg/kg) orally for 5 days and DA (3.5 mg/kg) IM stat). Dogs were infected intraperitoneally with 5 x 105 trypanosomes and treatment started 14 days post-infection. Data on parasitaemia, hematology and rectal temperature were recorded. Parasitaemia cleared within 3 days in all the SEC-DA treated dogs and there was no relapse parasitaemia. Parasitaemia did not clear in DA monotherapy dogs. All the SEC-DA treated dogs showed significantly (P < 0.05) higher leucocyte counts, red blood cell count, packed cell volume, hemoglobin concentration and lower rectal temperature than DA monotherapy. It was, therefore, concluded that SEC-DA combination is therapeutically more efficacious than DA monotherapy in the late treatment of T.b. brucei infection in dogs.

Desenlaces clínicos en una cohorte colombiana de pacientes con síndrome de flujo vaginal tratadas con antimicóticos y antibióticos / Clinical outcomes in a Colombian cohort of patients with vaginal discharge syndrome treated with antifungals and antibiotics

Resumen Objetivo: Reportar el desempeño clínico de dos medicamentos indicados para tratamiento del síndrome de flujo vaginal (fluconazol, secnidazol y terconazol, clindamicina) y comparar el efecto clínico. Materiales y métodos: Estudio observacional, comparativo y analítico de cohortes al que se incluyeron pacientes con diagnóstico de síndrome de flujo vaginal susceptibles de ser tratadas con fluconazol-secnidazol o terconazol-clindamicina en 12 ciudades de Colombia, con seguimiento de 8 días (± 3 días). Este proyecto fue aprobado por un comité de ética en investigación con seres humanos. Resultados: Se incluyeron 176 pacientes, pero solo 153 (87%) completaron el seguimiento. Los límites de edad fueron 18 y 67 años; 134 (76%) iniciaron con fluconazol-secnidazol y 42 (24%) con terconazol-clindamicina. Por lo que se refiere a la comparación en disminución de los síntomas, fluconazol-secnidazol y terconazol-clindamicina: flujo (p = 0.0000), prurito (p = 0.002), irritación (p = 0.0000), mal olor (p = 0.001) y dispareunia (p = 0.4). Conclusión: La prescripción de la combinación fluconazol-secnidazol fue más frecuente. El apego al tratamiento fue de 86%. La proporción de disminución de los síntomas tuvo límites de 15 y 40%; para el flujo vaginal fue superior a 70% (fluconazol-secnidazol: 115 de 121 y terconazol-clindamicina: 29 de 41).

Abstract Objective: To know the real life clinical performance of the prescription of two drugs for the treatment of vaginal discharge syndrome (Fluconazole-Secnidazole and Terconazole-Clindamycin) and to compare the clinical outcomes. Materials and methods: An analytical cohort study was conducted. We included women older than 18 years with a diagnosis of vaginal discharge syndrome who were candidates to be treated with Fluconazole-Secnidazole or Terconazole-Clindamycin with 8 days (±3) of follow-up, in 12 cities of Colombia. This project was approved by a research with human being's ethics committee. Results: 176 patients were included, 153 (86.9%) completed the follow-up, their age ranged between 18 and 67 years. 134 (76.1%) started treatment with Fluconazole-Secnidazole and 42 (23.8%) Terconazole-Clindamycin. Symptoms improvement was compared (Enrollment vs. Control), finding for Fluconazole-Secnidazole and Terconazole-Clindamycin: discharge (p=0.0000), pruritus (p=0.002), irritation (p=0.0000), bad smell (p=0.001) and dyspareunia (p=0.4). Conclusions: The prescription of the combination Fluconazole-Secnidazole was more frequent. The adherence to treatment was 86%. The proportion of improvement in symptoms ranged between 15% and 40%, however, for the case of vaginal discharge it was greater than 70% (Fluconazole-Secnidazole: 115/121 and Terconazole-Clindamycin: 29/41).

Determination and validation of secnidazole in tablets by UV spectrophotometric / Determinação e validação do secnidazol em comprimidos por espectrofotometria na região do ultravioleta

Secnidazole, a 5-nitroimidazole, is a drug used in the treatment against protozoa, and several bacterial infections. This study purpose was to develop and validate a UV spectrophotometric method to determine secnidazole in pharmaceutical tablet dosage forms once there is no method reported in the pharmacopoeia yet. The quantification was performed using methanol as solvent at 325 nm (maximum wavelength) and three kinds of products marketed in Brazil (reference, generic and similar tablets) containing 1g of secnidazole. The method obeyed Beer's law in the concentration range of 4 - 20 µgmL-1 respectively. The method was validated according to the International Conference on Harmonization (ICH) and Brazil National Health Surveillance Agency (ANVISA) guidelines, showing accuracy, precision, selectivity, robustness and linearity. Tests such as weight range, friability, disintegration, hardness and dissolution were carried out to check tablets' quality and all the trials showed to be in accordance with the general test guidelines of the Brazilian Pharmacopoeia. The dissolution test was carried out and the developed method was applied. The method developed is suitable for the estimation of secnidazole in tablets without any interference from the excipients and can be used for routine in quality control. Still, it's a simple, fast and low cost method.

Secnidazol, um nitroimidazólico, é um fármaco utilizado no tratamento para protozoários, e várias infecções bacterianas. Este trabalho propôs o desenvolvimento e validação de um método espectrofotométrico na região do ultravioleta para a determinação de Secnidazol na forma farmacêutica de comprimidos, uma vez que não há nenhum método relatado nas farmacopeias. A quantificação foi realizada utilizando metanol como solvente a 325 nm (máximo de comprimento de onda) e usando três tipos de produtos comercializados no Brasil (de referência, genéricos e comprimidos similares) contendo 1g de Secnidazol. O método obedeceu a lei de Beer no intervalo de concentração de 4 - 20 µgmL-1, respectivamente. O método foi validado de acordo com a Conferência Internacional de Harmonização (ICH) e diretrizes da Agência Nacional de Vigilância Sanitária do Brasil (ANVISA), apresentando exatidão, precisão, seletividade, robustez e linearidade. Testes como variação de peso, friabilidade, desintegração, dureza e dissolução foram realizados para verificar a qualidade de comprimidos e mostrou-se de acordo com os testes gerais da Farmacopeia Brasileira. O teste de dissolução realizado e o método desenvolvido pode ser aplicado. O método desenvolvido é adequado para a estimativa de secnidazole em comprimidos sem qualquer interferência dos excipientes e pode ser usado para a rotina de controlo de qualidade. Ainda, é um método simples, rápido e de baixo custo.

Efectividad y seguridad de la combinación fluconazol más secnidazol para el tratamiento de flujo vaginal sintomático: Bogotá, Colombia / Effectiveness and safety of the combination of fluconazole and secnidazole for the treatment of symptomatic vaginal discharge: Bogotá, Colombia

Objectives: To describe the safety and the clinical and microbiological efficacy of a single oral dose of a combined treatment with secnidazole plus fluconazole for the syndromic management of symptomatic vaginal discharge.Materials and methods: A clinical trial without control group study was conducted including women with symptomatic vaginal discharge who assisted to a secondary level hospital in Bogota, Colombia. 118 women were included in a consecutive convenience sample who received the study treatment according to syndromic diagnosis approach. Microbiological diagnosis of bacterial vaginosis (BV) was confirmed by Nugent score, yeast infection by candida culture and trichomoniasis by wet mount. Prevalence, clinical and microbioogical efficacy and safety of the secnidazole and fluconazole combination pill was determined and a sensitivity analysis for treatment efficacy was performed.Results: The following infections were found: BV in 57.1%, candidiasis in 28.8%, and mixed infections in 10.8%. In 8.5% of the patients, the microbiology tests were negative. No trichomonas were found. The clinical cure rate was 90.4%, and the microbiological cure rate was 94.1% with the study medication. Twelve cases (12.90%) presented drug-related non serious adverse events.Conclusion: The most prevalent infection was BV, followed by candidiasis and mixed infection. The combination of a single dose of secnidazole plus fluconazole combined pill had an efficacy rate over 90% and was safe for the treatment of symptomatic women with vaginal discharge.

Objetivos: describir la seguridad y la eficacia clínica y microbiológica del tratamiento combinado de secnidazol mas fluconazol oral, dosis única, para el manejo del flujo vaginal sintomático.Materiales y métodos: ensayo clínico sin grupo control, realizado en mujeres sintomáticas con flujo vaginal en un hospital de mediana complejidad localizado en la ciudad de Bogotá, Colombia. Se incluyeron 118 mujeres por muestreo consecutivo por conveniencia quienes recibieron el tratamiento de acuerdo con el diagnóstico sindrómico. El diagnóstico microbiológico se estableció usando el puntaje de Nugent para vaginosis bacteriana (VB), el cultivo para cándida y el frotis directo en fresco para tricomonas. Se estimaron la prevalencia, la efectividad clínica y microbiológica, y la seguridad del tratamiento combinado de secnidazol con fluconazol en mono dosis, y se realizó un análisis de sensibilidad para la eficacia del tratamiento.Resultados: la prevalencia de VB fue del 57,1%, de candidiasis fue del 28,8% y de la infección mixta 10,8%. No se encontró infección por tricomonas. En 8,5% de las pacientes los resultados microbiológicos fueron negativos. La tasa de curación clínica con secnidazol más fluconazol fue de 90,4%, y la tasa de curación microbiológica fue de 94,1%. Doce pacientes (12,90%) presentaron eventos adversos no serios relacionados con el medicamento.Conclusión: la VB fue la infección más común en este estudio, seguida por la candidiasis y las infecciones mixtas. La combinación secnidazol más fluconazol es una intervención efectiva para alcanzar la cura clínica y microbiológica en las pacientes con síndrome de flujo vaginal, con una baja frecuencia de eventos adversos no serios.

Genotoxic evaluation of ornidazole and secnidazole in albino mice: an experimental study.

Background: The present study was planned to explore the genotoxic potential of some commonly used antimicrobials like ornidazole and secnidazole in swiss albino mice. Methods: Therapeutic equivalent doses of ornidazole and secnidazole were given by intra peritoneal route. Single dose in individual groups of mice (n=5 in each) was administered for acute study. Doses were repeated every 24 hrs for 7 times in additional groups of mice (n=5 in each) for sub-acute study. Cyclophosphamide served as positive control while normal saline as negative control. After 24 hrs of single dose (acute study) and last dose of drug administration in sub-acute study, about 0.5 ml of blood was collected by retro orbital sinus for comet assay as described earlier (Rojas E et al, 1999) and later the mice were sacrificed to aspirate the femoral bone marrow for micronucleus test as described earlier by described by Schmid W (1975). In comet assay, the total comet length and head diameter was measured under microscope using ocular & stage micrometer to calculate comet tail length. In micronucleus assay, the stained bone marrow tissue smears were scored for the frequency of micronucleated polychromatic erythrocytes (MnPCE) and also the ratio between polychromatic erythrocytes (PCE) to normochromic erythrocytes (NCE) was obtained. Results: It was analyzed by one-way ANOVA followed by Dunnet’s multiple comparison tests. Significant (P< 0.01) increase in comet tail length and percentage of micronucleated polychromatic erythrocytes (% MnPCE) was observed in groups treated with single and multiple doses of Cyclophosphamide whereas ornidazole and secnidazole treated groups did not show any significant changes. Conclusions: The results indicate that Ornidazole and secnidazole are devoid of genotoxicity.

Bioavailability of two oral formulas of secnidazole in healthy volunteers / Biodisponibilidade de duas fórmulas de secnidazol oral em voluntários saudáveis

Secnidazole is an antimicrobial agent used primarily in the treatment of amoebiasis. For this bioequivalence study of secnidazole, twenty-eight healthy female volunteers were enrolled in a randomized crossover study. Each volunteer was given a single oral dose of secnidazole test preparation and then the reference preparation, or vice versa, with a wash out interval of two weeks. The plasma concentrations of secnidazole were determined by HPLC, and the samples were extracted with tert-butyl-methyl-ether: dicloromethane (60:40, v/v). Secnidazole and its parent compound metronidazole were separated on a C18 column with water:acetonitrile (85:15, v/v) as the mobile phase, and monitored at 310 nm. The ratio of mean Cmax, AUC0-t and AUC0-∞ values for the test and reference products were within the predetermined range established by ANVISA, demonstrating that the two formulations are bioequivalent in rate and extent of absorption.

Secnidazol é um agente antimicrobiano utilizado principalmente no tratamento da amebíase. Para este estudo de bioequivalência de secnidazol em voluntários saudáveis, foram incluídos vinte e oito voluntárias mulheres no estudo randomizado cruzado. Cada voluntária recebeu uma única dose oral de secnidazol do produto teste e referência para comparação, com um intervalo de wash-out de duas semanas. As concentrações plasmáticas de secnidazol foram determinados por CLAE, as amostras foram extraídas com terc-butil-metil-éter: dicloromethano (60:40, v/v). O secnidazol e seu padrão interno metronidazol foram separados em uma coluna (C18 ) com fase móvel água ultra-pura:acetonitrila (85:15, v/v) e monitorado em 310 nm. As razões entre as médias geométricas de Cmáx, ASC0-t e ASC0-∞, encontraram-se dentro do estabelecido pela ANVISA, demonstrando que as formulações são bioequivalentes quanto à taxa e extensão de absorção.

Determination of secnidazole and its related substances by HPLC / 中国药科大学学报

Aim: To establish an HPLC method for the determination of secnidazole and its related substances, and to elucidate the structure of the main related substances. Methods: HPLC was performed on an Agilent C_(18) (150 mm × 4. 6 mm, 5 μm) column. The mobile phase consisted of acetonitrile and 0. 1% formic acid solution( 10 : 90). The detection wavelength was set at 320 nm and the column oven was maintained at 30 ℃. The mass spec-trometry detector was equipped with an ESI source with a temperature of 350 ℃, and set at positive ion monito-ring model The spray chamber pressure was 0. 34 MPa. The drying gas flow rate was 10 L/min. Results: Sec-nidazole was completely separated from the impurities. The calibration curve of secnidazole was linear over the range of 0. 10-1 500. 0 μg/mL with the correlation coefficient of 0. 999 9. The contents of secnidazole in the sam-ples were 100.5%, 100.3% and 100.7%, respectively, and those of the related substances were 0.463%, 0. 488% and 0.465%, respectively. The three related substances were identified by HPLC-UV-MS~n as 2-methyl-5-nitroimida-zole and the isomerides of secnidazole, respectively. Conclusion: The developed method is reliable for the quality control and determination of related substances of secnidazole.

Secnidazole for metronidazole-resistant amebiasis

It is presented the case of a patient with intestinal colonization by Entamoeba histolytica, Entamoeba coli e Iodamoeba butschilli. Two treatments with metronidazole did not eradicate the protozoans, however, a treatment with secnidazole showed to be effective.

Apresenta-se uma mulher com colonização intestinal por Entamoeba histolytica, Entamoeba coli e lodamoeba butschilli. Dois tratamentos com metronidazol oral não erradicaram os protozoários, porém, um tratamento com secnidazol mostrou-se eficaz.

Bioequivalence evaluation of secnidazole tablets in healthy male volunteers / 中国临床药理学与治疗学

AIM: To compare the bioavailability of the test and reference formulation of secnidazole (2 g) tablets under fasting conditions. METHODS: This bioequivalence study was carried out in 20 healthy male Chinese volunteers according to a single dose, two-sequence, crossover randomized design. Fifteen blood samples per period were collected over 96 h, and plasma secnidazole concentrations were determined by locally validated high performance liquid chromatography (HPLC) assay and pharmacokinetic parameters were analyzed by the non-compartmental and compartmental methods. RESULTS: Plasma concentration-time profiles were adequately described by a one-compartment open model with first-order absorption. The main pharmacokinetic parameters of secnidazole test and reference tablets were as follows: tmax were (2.30±1.06) and (2.28±1.10) h, Cmax were (49.63±6.35) and (46.17±4.24) mg/L, t1/2 were (28.84±3.41) and (29.05±4.01) h, AUC0-96 were (1832.06±180.15) and (1847.14±204.14) mg·h-1·L-1, respectively. The relative bioavailability of test tablets was (99.99±11.92)%. CONCLUSION: The results indicate that the two formulations of secnidazole tablets are bioequivalent in the rate and extent of absorption.

Pharmacokinetics and Bioequivalence of Secnidazole in Human Body / 中国药房

OBJECTIVE:To evaluate the bioequivalence of domestic secnidazole tablet,capsule and imported secnidazole tablet in healthy volunteers.METHODS:18healthy volunteers were randomly divided into3groups according to a triple-cross design,all the volunteers were given a single dose of1g secnidazole,the interval for washout period of3times adminis?tration was14days.The plasma drug concentration of secnidazole was determined by HPLC-UV.RESULTS:The main pharmacokinetic parameters of homemade tablet and homemade capsule and imported tablet were as follow,t max were(2.00?1.93),(2.67?2.14)and(1.54?1.53)h respectively,t 1/2 were(28.56?4.98)、(29.69?6.81)and(27.16?5.06)h,C max were(25.50?2.74),(24.27?3.76)and(25.64?4.10)?g/ml respectively.AUC 0～t were(736.03?73.20),(704.78?88.51)and(737.77?76.02)(?g?h)/ml respcetively.AUC 0～∞ were(886.36?114.50),(864.57?172.27)and(870.64?100.21)(?g?h)/ml respectively.The relative bioavailability of homemade tablet was(100.02?6.73)%,and that of homemade capsule was(95.91?10.66)%.CONCLUSION:3preparations of secnidazole are bioequivalent.

Formulation Design and Content Determination of Thermosensitive Secnidazole Hydrogels / 中国药房

OBJECTIVE:To select the optimal formulation of thermosensitive secnidazole hydrogels and establish its determination method. METHODS:Formulation was optimized by orthogonal design with the content of poloxamer P407/P188(A),ethanol (B)and sodium alginate(C)as factors and with secnidazole as index. The content of secnidazole in preparation was determined by UV spectrometry at detection wavelength of 277 nm. RESULTS:The optimal formulation was as follows:A of 15 g/15 g,B of 20 mL and C of 0.6 g. The linear range of secnidazole was 4.618～46.18 mg?L-(1r=0.999 8)with an average recovery of 98.27%. The RSD of intra-day and inter-day were both lower than 1.8% and 2.1% respectively. CONCLUSIONS:The formulation is reasonable and the process was reliable and controllable in quality.

Determination of Secnidazole in Secnidazole Tablets by RP-HPLC / 中国药房

OBJECTIVE:To determine the contents of secnidazole in secnidazol e tablets by RP-HPLC.METHODS:The chromatographic column was VP-ODS C 18 with acetonirile-0.05mol/L potassium dihydrogen phosphate-triethylamine(15∶85∶0.4)as the mobile phase,the detection wavelength was311nm and the flow rate was0.8ml/min.RESULTS:There was a good linear relationship when the sample size was within the range of0.166?g～0.832?g(r=0.9999),the average re?covery was99.84%(RSD=1.05%,n=15).CONCLUSION:The method is simple and accurate,sensible and reproducible,which can be used for the assaying of both the raw materials and preparations and the quality control of secnidazole tablets.

Ensaio terapêutico na infecção por Giardia muris em camundongo com metronidazole, tinidazole, secnidazole e furazolidone / A therapeutic trial in Giardia muris infection in the mouse with metronidazole, tinidazole, secnidazole and furazolidone

Foi testado in vivo a sensibilidade de Giardia muris a quatro drogas comumente usadas no tratamento da giardíase humana. Foram utilizados 7 grupos de animais, com 12 camundongos cada, sendo que o grupo controle recebeu apenas solução salina 0,15M (0,5ml/animal). Os demais grupos receberam em dose única: metronidazole e furazolidone (500mg/kg), tinidazole e secnidazole (200mg/kg). A eficácia das drogas foi avaliada através da contagem de cistos nas fezes e pela ausência de trofozoítos no intestino. O metronidazole foi a droga mais eficaz. Os cortes histológicos mostraram diferenças entre o padrão da mucosa intestinal de animais normais e parasitados. No entanto, não se observou diferença entre o padrão de mucosa de animais infectados tratados e não tratados, o que sugere que estas alterações podem ser causadas pelo parasito e não pelas drogas.

A comparative study about the effectiveness of metronidazole, tinidazole, secnidazole and furazolidone was performed on Giardia muris from mice naturally infected. Groups of 12 animals each was constituted: the control treated with saline; one treated with metronidazole; one treated with furazolidone; one treated with tinidazole; one treated with secnidazole; histological normal control; histological infected. Samples of three stools were examined before and after treatment with quantification of cysts. Animals were cured when the trophozoites was not seen in the small bowel. The curative activity of drugs was 58.3% for metronidazole, 50% for furazolidone, 40% for secnidazole and 16% for tinidazole. It was also showed that there was a different pattern of the intestinal mucosa from the control and infected groups, treated or not, suggesting that the alterations encountered in the mucosa of infected animals were due to the parasitism either the action of the drugs.

A clinical traial of secnidazole in the treatment pericoronitis / 实用口腔医学杂志

0.05).Conclusion:Secnidazole is effective and safe in the treatment of pericoronitis.

In Vitro Effect of Secnidazole Benzoate on Trichomonas vaginalis / 中国寄生虫学与寄生虫病杂志

Objective To research the trichomonacidal effect of secnidazole benzoate in vitro.Methods Trichomonas vaginalis was cultured in liver extract medium in 96-well microplate.The culture suspension of Trichomonas vaginalis was divided into four groups:secnidazole benzoate, secnidazole, metronidazole and control, with medium as blank control.MTT colorimetric assay was applied to determine the inhibitory effect of secnidazole benzoate on the proliferation of Trichomonas vaginalis.The culture suspension was transfered into test tubes and divided into same groups to observe inhibitory effect by the classical microscopic counting method.Results After 24 h incubation, the proliferation of the parasites was concentration-dependent by secnidazole benzoate(t=9.02, P