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Objective To establish a quality control method for Lvxintong Rugao. Methods Ketoconazole, Halcinonide and Neomycin sulfate were identified by TLC. The content of Ketoconazole and Halcinonide were determined by HPLC. The chromatographic column of Agilent ZORBAX SB-C18 (4.6 mm×150 mm, 5 μm) column was used. Methanol-phosphate buffer (pH=7.40, 75:25) was applied as the mobile phase. The detection wavelength was 235 nm. The flow rate was 1.0 ml/min and the column temperature was set at room temperature. Neomycin Sulfate was determined by polarimetric analysis. Results The identification and determination methods showed good specificity. Ketoconazole and Halcinonide displayed good linearity within the range of 1.999~39.98 μg (r=0.999 9) and 0.400 8~8.016 μg (r=0.999 9), respectively. The average recoveries were 97.75% (RSD 0.77%) and 97.57% (RSD 0.84%), respectively. For the determination of Neomycin Sulfate, r=0.999 6 (n=6) in the range of 130.4~2 608 U/ml (n=6). The precision and repeatability of RSD were 1.1% and 1.6%, respectively. The solutions were stable in 6 h and the average recovery was 98.8% (RSD 2.6%). Conclusion The method could be used as the quality control method for Lvxintong Rugao.
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Objective To establish a RP-HPLC method for determination of ketoconazole, mupirocin and mometasone furoate in compound ketoconazole ointment. Methods RP-HPLC was conducted on a Intersil ODS-3 column (250 mm×4.6 mm, 5 μm), with methanol-PBS with pH 5.5 (65:35) as the mobile phase and the column temperature was 45 ℃. The flow rate was 1.0 ml/min, and the detection wavelength was 248 nm. Results The methodological verification showed that ketoconazole, mupirocin and mometasone furoate had a good linearity (r≥0.9995). The inter/intra-day precisions were less than 3.0%, The recovery rates were between 90% and 108%. The stability and repeatability of RSD were also less than 3.0%, which met the requirements of method validation. The contents of the three components in three batches were determined by the new method. Conclusion The method is simple and reliable. It can provide a basis for the quality control of compound ketoconazole ointment and lay a foundation for its quality standard research.
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Background: Fungal infections of the skin were the 4th most common skin disease in 2010 affecting 984 million people. An estimated 20-25% of the world抯 population has some form of fungal infection. Dermatophytes are fungi that cause superficial infections of the skin, commonly referred to as tinea infections.Methods: This was a prospective and an observational study conducted from February 2018 to January 2019 in Dermatology Department. Prescriptions included all newly diagnosed patients with cutaneous fungal infection of both sex who attended dermatology OPD. Factors considered were sociodemographic parameters, the disease encountered and number of patients in each group and number of patients who received antifungal therapy (oral and topical) etc.Results: 1000 prescriptions were analysed of patients between 18 to 65 years of age with cutaneous fungal infections. There were a greater number of males (57.4%) than females (42.6%). The average number of antifungal drugs prescribed per prescription was 2.33. Majority of the patients were prescribed itraconazole (82.30%) followed by terbinafine (9.70%) and fluconazole (8.0%).Conclusions: The most common oral antifungal drug used was itraconazole. Ketoconazole and Terbinafine were the most commonly used topical agents respectively.
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Background: Onychomycosis is one of the most common fungal nail infections caused by Dermatophytes, Non-Dermatophytic Molds (NDM) and Yeast. Though it is not life-threatening, can cause pain, discomfort, and disfigurement. It decreases the nail growth rate. Objectives: This study was carried out to document the clinico-mycological pattern and antifungal susceptibility pattern of onychomycosis.Methods: The study group included 130 consecutive patients with suspected fungal nail infections, attending Dermatology outpatient department of King George Hospital, Visakhapatnam, Andhra Pradesh during November 2012 to August 2014. The nail clippings of the patients were collected and subjected to KOH mounts for direct microscopy and fungal culture and antifungal susceptibility tests.Results: Onychomycosis was common among males (66.92%) than females (33.08%) with highest incidence was in age group 31-40 years (41.37%). Finger or toenails were exclusively involved in 32.18% and 55.18% patients respectively while these were involved concurrently in the rest of the 12.65% patients. Distal and lateral subungual onychomycosis seen in 64.36% of the patients was the most common clinical type. KOH and culture positivity were recorded in 56.92% and 48.46% cases respectively. Dermatophytes (50.58%) were predominant isolate followed by NDM (27.58%) and yeast (21.84%). Clotrimazole and ketoconazole were most effective antifungals against dermatophytes. For NDM, itraconazole, nystatin and amphotericin B and for yeast fluconazole and itraconazole were effective.Conclusions: The present study gives an insight about the aetiological agents causing onychomycosis and their anti-fungal susceptibility pattern in this region. Thus, it can help in taking adequate control measures to prevent it.
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Ion-pairing liquid chromatographic method was validated for determination of ketoconazole in shampoo and cream samples as per ICH guidelines. The chromatographic conditions were carried out in the isocratic mode using a mixture of methanol and 8 mM sodium dodecyl sulfate (pH 5.5) in a ratio of 45:55 v/v %, as mobile phase. The flow rate was set at 1.0 mL min-1. Chromolith RP-18e (100×4.6 mm) was used as the analytical column with a fluorescence detection at an excitation wavelength of 260 nm and an emission wavelength of 375 nm. The average percentage recovery of shampoo A, shampoo B, shampoo C, cream A and cream B were 99.88, 97.06, 99.58, 96.77 and 97.26, respectively. The limit of detection was 0.12 mg L-1. The drug decomposition under acid degradation, base degradation and oxidative degradation were found to be in the range of 91.63-94.70% indicating that the drug is resistant towards acidic conditions. The drug decomposition under thermal condition and photolysis condition were found to be in the range of 69.05-87.15% and 47.31-66.83% respectively, indicating that the drug decomposition is more sensitive under photolysis conditions. This method is suitable for the quality control of ketoconazole in commercial shampoo and creams.
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@#Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multidrug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies suggest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CELLO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobacterial agents.
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OBJECTIVE：To excavate the safety warning signals induced by azole antifungal agents ，including fluconazole ， ketoconazole，itraconazole and voriconazole after marketing ，and to provide references for rational drug use in the clinic. METHODS：Reporting odds ratio （ROR）data mining algorithm was used to investigate signals of adverse drug event （ADE）for fluconazole，ketoconazole，itraconazole and voriconazole from FDA Adverse Event Reporting System （FAERS）during January 1st，2004 to March 30th，2019. ROR data mining method was used to excavate the ADR signals of the drugs ，and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS ：A total of 27 831，5 712， 5 381 and 11 333 reports were picked out for fluconazole ，ketoconazole，itraconazole and voriconazole ，respectively. All of these drugs had exhibited high-risk signals detection by ROR ，including medical examination ，blood and lymphatic system disorders ， renal and urinary disorders ，endocrine diseases ，hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole （fluconazole ROR ＝6.51，voriconazole ROR ＝14.65）；ADR detection results of Cushing’s-like syndrome （ROR＝24.86） and adrenal suppression （ROR＝44.06） by itraconazole showed high-risk signals ； ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction （ketoconazole ROR ＝15.64， itraconazole ROR ＝23.26），and the signal intensity of ketoconazole （ROR＝2.81）in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ，hemorrhagic cystitis caused by fluconazole，itraconazole and voriconazole were not included in the drug instructions （fluconazole ROR ＝17.73，itraconazole ROR ＝31.43，voriconazole ROR ＝17.06）； netted green spot caused by fluconazole （ROR＝10.50）were not included in the drug instructions . CONCLUSIONS：Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ，ketoconazole，itraconazole and voriconazole ； particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole，itraconazole，voriconazole and netted green spot caused by fluconazole ，as well as ADRs mentioned in the drug instructions but have abnormally high signal ，such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .
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Objective To evaluate the pharmacodynamics and safety of the self-made compound ketoconazole ointment. Methods Using the disk diffusion test, 6 kinds of fungi and 2 kinds of bacteria were selected to investigate the effect of the self-made ointment and 3 commercial products on the diameter of the bacteriostatic circle. In addition, the skin irritation and skin allergies of the single and multiple applications were used to evaluate the safety of the self-made ointment. Results The self-made ointment was similar to the commercial products containing ketoconazole. They all showed remarkable bacteriostatic circle against the 6 kinds of fungi. For pseudomonas aeruginosa, none of the preparations contributed to visible bacteriostatic circle. For staphylococcus aureus, the bacteriostatic circle of the self-made ointment was similar to that of commercial mupirocin ointment and was significantly larger than other commercial products. After the treatment with the self-made ointment, the score of the skin irritation was below 0.5 and the sensitization rate was 0. There was no difference in tissue structure between treated and normal skin. Conclusion The self-made compound ketoconazole ointment has better safety and better antibacterial property than the commercial products. It is expected to be used for the treatment of superficial skin fugle infections.
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Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qua-litative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ke-toconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation pro-ducts, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.
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Introdução: aproximadamente 75% das mulheres saudáveis experimentam pelo menos um episódio sintomático de candidíase vulvovaginal (CVV) durante sua vida. Objetivo: avaliar a atividade antifúngica contra cepas de C. tropicalis dos enantiômeros (R)-(+) e (S)-(-)-citronelal [(R)-(+) e (S)-(-)-CT] em associação com cetoconazol. Metodologia: o efeito antifúngico de ambos os enantiômeros foram quantificados e classificados como fungicida ou fungistático a partir dos resultados obtidos da microdiluição em meio líquido RPMI1640 para a obtenção da concentração inibitória mínima (CIM) e da concentração fungicida mínima (CFM). Foram realizados ensaios de associação do antifúngico padrão, cetoconazol com os fitoconstituintes por difusão em Agar e os resultados foram classificados como sinérgicos, antagônicos e indiferentes. Resultados: a CIM50 e a CFM50 dos compostos (R)-(+) e (S)-(-)-citronelal foram respectivamente 16 e 64µg/mL e 2×CIM. Houve sinergismo para todas as cepas testadas com ambos os compostos, porém com maior efeito do enantiômero (S)-(-)-CT sobre as cepas LM 665 e LM 255 em relação ao enantiômero (R)-(+)-CT. Conclusão: os compostos naturais deste estudo mostraram efeito fungicida sobre as cepas testadas, bem como efeito sinérgico significativo quando associado ao cetoconazol
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Female , Candida tropicalisABSTRACT
RESUMEN Objetivo Realizar la notificación y verificar el seguimiento de cinco alertas sanitarias de medicamentos a un grupo de prestadores de salud en Colombia. Métodos Estudio cuasi-experimental, prospectivo, antes y después, sin grupo control, mediante una intervención en médicos prescriptores de ketoconazol, metoclopramida, nimesulida, diacereina, ranelato de estroncio. Se tomó como población universo a los afiliados al régimen contributivo del Sistema de Salud Colombiano en 13 entidades promotoras de salud (EPS) de Colombia. Se identificaron los pacientes que recibían mensualmente estos medicamentos previamente a la alerta. Se realizó una intervención educativa y posteriormente se midió la proporción de cambio en la dispensación. Resultados Se realizaron en total unas 26 actividades diferentes a 500 médicos prescriptores. De un total de 4 121 954 de personas se identificaron 13 979 pacientes mensuales en 2013 que recibían alguno de los cinco medicamentos y se observó una reducción en 1 470 sujetos al mes (-10,5%) para 2014. El medicamento con el que se consiguió la mayor reducción fue ketoconazol (-31,1% de casos), seguido de ranelato de estroncio (-30,3%) y metoclopramida (-8,6%). Para nimesulida (+0,7%) y diacereina (+16,4%) no se obtuvieron resultados favorables. Conclusiones Se mantienen prescripciones potencialmente riesgosas en pacientes de Colombia. Con intervenciones basadas en farmacovigilancia posterior al reporte de alertas por agencias reguladoras sanitarias, se puede disminuir la proporción de pacientes que utilizan estos medicamentos.(AU)
ABSTRACT Objective Make the notification and monitoring compliance with five health drug alerts to a group of health care providers in Colombia. Methods Quasi-experimental, prospective, before-after study, without control group, by intervening in physician prescribers of ketoconazole, metoclopramide, nimesulide, diacerein, strontium ranelate. The affiliated population of the contributory system of the Colombian Health System was taken as the universe population sample from 13 health promoting entities (EPS) of Colombia. Patients receiving monthly these drugs prior to the alert were identified. An educational intervention was performed and then the rate of change in the dispensation was measured. Results About 26 different activities were conducted on 500 prescribers. Out of a total of 4 121 954 people, 13 979 patients were identified monthly in 2013, who received some of the five medications. Likewise, a reduction in 1,470 subjects per month (-10.5%) for 2014 was observed. The drug which achieved the greatest reduction was ketoconazole (-31.1% of cases), followed by strontium ranelate (-30.3%) and metoclopramide (-8.6%). For nimesulide (+ 0.7%) and diacerein (+ 16.4%) no favorable results were obtained. Conclusions Patients with potentially risky prescriptions remain in Colombia; educational pharmacovigilance interventions made after the report alerts given by drug regulatory agencies may decrease the proportion of patients using these drugs.(AU)
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Humans , Drug Utilization/standards , Medical Order Entry Systems/organization & administration , Pharmacovigilance , Deprescriptions , Prospective Studies , Non-Randomized Controlled Trials as Topic/instrumentation , Ketoconazole/supply & distribution , Metoclopramide/supply & distributionABSTRACT
Objective To study the in situ intestinal absorption characteristics of cyclovirobuxine D (CB) hydroxypropyl-β-cyclodextrin inclusion complex (CBHD) in rats, and to explore the effect of cytochrome P450 inhibitor ketoconazole (KET) on CB and CBHD in situ intestinal absorption. Methods Twenty-four male rats were randomized into CB, CBHD, KET+CB and KET+CBHD groups, with 6 rats in each group. In situ intestinal absorption was adopted in a rat model. One-way intestinal perfusion model was employed to investigate the absorption of CB and CBHD in the intestinal segments of rats and the effects of KET on CB and CBHD absorption. The concentration of CB was determined by highperformance liquid chromatography with fluorescence detector (HPLC/FLD; Lichrospher C18 column [250 mm×4.6 mm, 5 μm]). The mobile phase was methanol-water with volume ratio being 85: 15. The excitation wavelength was set at 231 nm, and emission wavelength was set at 385 nm. The column temperature was 25 °C, and flow rate was 1.0 mL/min. The injection volume was 20 μL. Results The specificity of HPLC/FLD method was good and the standard curve equation was A=106.7 C+41.861 (R2=0.999 08) based on the linear regression of CB concentration (C) with CB peak area (A), indicating that the CB mass concentration was linear in the range of 0.5 to 20.0 μg/mL. The intra-day precision of the 1.0, 5.0 and 10.0 μg/mL samples was 2.25%, 2.44% and 3.04%, and the inter-day precision was 4.22%, 2.00% and 2.50%, respectively. The precision was good and the method was in accordance with the requirements of methodology. The recovery rates of the 1.0, 5.0 and 10.0 μg/mL samples were 99.08%, 98.24% and 97.25%, respectively, which were also in accordance with the requirements of methodology. The intestinal absorption rate constant (Ka) values of CBHD with KET were 4.18, 5.05, 1.91 and 2.85 times those of CB, and the effective permeability (Peff) values were 4.92, 5.98, 2.19 and 3.24 times those of CB in the duodenum, jejunum, ileum and colon, respectively (all P<0.05). Conclusion KET can improve the intestinal absorption of CB and CBHD in rats.
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Objective:To establish a method for the content determination of two ingredients in ktoconazole and clobetasol propio -nate cream.Methods:HPLC was performed on a Kromasil C 18 column (250 mm ×4.6 mm, 5 μm) with the mobile phase of metha-nol-sodium acetate with gradient elution at a flow rate of 1.0 ml· min-1 .The detection wavelength was 239 nm, the column tempera-ture was 30℃and the injection volume was 10 μl.Results:The linear range was 160.30-1282.40 μg· ml-1 for ketoconazole (r=1.0000) and 4.03-32.24μg· ml-1 for clobetasol propionate (r=1.0000).The average recoveries were 100.9％(RSD=0.52％, n=9) and 100.2％(RSD=0.56％,n=9), respectively.Conclusion:The method is accurate with good specificity and high sensi-tivity, which can be used for the detection of ketoconazole and clobetasol propionate .
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Objective:To evaluate efficacy of combined therapy with ozonated water and oil on patients with tinea pedis.Methods:A total of 60 patients with tinea pedis were divided into 2 groups in a randomized and blinded test.Patients in a control group were treated with naftinfine hydrochloride and ketoconazole cream once a day.Patients in an ozone group were treated with ozonated water bath and then ozonated oil topical application once a day.Patients in the 2 groups were treated for 4 weeks.Clinical and laboratory data were collected for both groups at the end of the 1st week,the 2nd week,and the 4th week.The Pearson chi-square was performed to compare scores of the clinical signs and symptoms (CSS) and the mycological result between the 2 groups.Independent samples T-test was performed to compare the curative effect between the 2 groups.Results:After 4 weeks' treatment,6 patients were positive in the control group determined by mycological examination while 1 patient was positive in the ozone group,with no significant difference between the 2 groups (P＞0.05).Changes in CSS at the end of the 1st week,2nd week,and 4th week were obtained and showed no significant difference between the 2 groups at the 3 different time points (P＞0.05).No side effects were observed.Conclusion:Combination of ozonated water with oil is effective on treatment oftinea pedis and it shows no side effects.
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Objective To evaluate the in vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex.Methods According to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines,the microdilution checkerboard method was used to evaluate in vitro antifungal activities of ketoconazole alone and in combination with tetrandrine against 21 clinical isolates of Candida parapsilosis complex based on the fractional inhibitory concentration index (FICI).Antifungal effects of the above drugs at different time points were evaluated by the XTT assay,and then time-killing curves were drawn and assessed to investigate the in vitro dynamic antifungal activity.Results The minimum inhibitory concentrations (MICs) of tetrandrine and ketoconazole alone against 21 clinical isolates of Candida parapsilosis complex were 32-64 mg/L and 0.031 25-2 mg/L,respectively.When ketoconazole was combined with tetrandrine,MICs of tetrandrine and ketoconazole were reduced to 2-8 mg/L and 0.008-0.25 mg/L respectively,and the FICI ranged from 0.09 to 0.5.The time-killing curves revealed that the fungal growth was delayed obviously in the combination group compared with the ketoconazole alone group and tetrandrine alone group.Conclusion Tetrandrine has obvious synergistic effects on ketoconazole against Candida parapsilosis complex in vitro.
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Objective To prepare compound ketoconazole ointment and perform the stability study .Methods Ketocon-azole ,mupirocin and mometasone furoate were used as active pharmaceutical ingredients (API) .PEG mixture was used as ma-trix to prepare the ointment .Stability of the API in the ointment was evaluated by the stress tests .Results The optimal ratio of PEG400 to PEG3350 for the ointment matrix was 2:1 .Mometasone furoate and mupirocin in the ointment were stable to the high temperature(40 ℃)while ketoconazole had some degradation .The stability of the API was improved by addition of 0 .5％ of L-A .During the accelerate test ,the ointment had no color change and the API percentages were above 98％ .Conclu-sion The novel compound ketoconazole ointment was successfully prepared and the formulation stability was excellent .
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La mucosa vaginal ha sido utilizada largamente para la administración de antimicrobianos destinados al tratamiento de infecciones endógenas del tracto genital inferior (IETGI) en mujeres embarazadas y no embarazadas. Candida spp elabora biopelículas (BP) y su formación es un proceso complejo que requiere que las células fúngicas establezcan múltiples interacciones con el medio. Las BP están rodeadas por un exopolímero (EPM) que puede restringir la actividad de anticuerpos, la difusión de sustancias y unirse a los antimicrobianos (AM), limitando su acción. Los antimicrobianos (AM) en general y los antimicóticos en particular (AMC) pueden tener dificultades para llegar a las células dentro del EPS. Muchas de las fórmulas que se emplean para el tratamiento empírico usan combinaciones inapropiadas con limitada o nula actividad sobre las biopelículas (BP). La presencia de moléculas que provoquen su inhibición anulando los inductores del EPM o por otro mecanismo, permitirá la actividad del AM específico. Objetivo: demostrar que la actividad de la clindamicina (CLI) en fórmula dual con ketoconazol (KET) actúa sobre BP Candida albicans (CA) y especies no albicans de Candida . (NAC). Métodos: estudiamos la actividad de clindamicina-ketoconazol (CK) sobre la adherencia y dispersión de BP de 8 aislamientos vaginales de CA y 7 de CNA. Se inocularon en 3 tubos con caldo Sabouraud y un dispositivo de vidrio para la formación de la BP según técnica ya descrita. Adherencia: Se incubaron durante 6 horas y se agregó una combinación de CK proveniente del material de óvulos, diluido convenientemente (62,5/260,4 ug/ml), a uno de los tubos de cada aislamiento tomándose como hora 0. Dispersión: esa misma dilución se agregó a otro tubo a las 16 horas. El tercer tubo quedó como testigo sin antimicrobianos. La lectura se efectuó con microscopio óptico a las 24 horas de agregada la combinación CK previa tinción con cristal violeta y se evaluaron con programas fotográficos. Por separado analizamos la actividad de CLI (62,5 ug/ml) y KET (260,4 ug/ml) con técnica similar. Seleccionamos las muestras de 7 pacientes que demostraron candidiasis vulvovaginal (CVV) y las estudiamos con la técnica de capas celulares. Se empleó la combinacion CK para el estudio de la adherencia y dispersión. Resultados: Adherencia se demostró poca influencia de CK en la adherencia con respecto a cada testigo. Dispersión: la influencia de CK se demostró en la mayoría de los aislamientos particularmente en los de CNA que mostraron una mayor presencia de EPM. Las hifas solo se observaron en 1/15 de los aislamientos de Candida spp cuando se agregó CK a las 16 horas. En las BP de las muestras clínicas no aparecieron hifas ni otro elemento micótico en 5/7 con respecto a los testigos. Conclusión: Según estos resultados el uso de una combinación de CK en BP de Candida spp, resulta en una adecuada penetración del AMC demostrada por la dispersión de la BP al cabo de 24 horas. Clindamicina no interfiere con la acción del ketoconazol sino que promovería su actividad anti-candida modificando posiblemente estructuras de superficie y la del EP por inhibición de las moléculas que facilitan la expresión del mismo. In vivo promueve la actividad inmunomoduladora que no se puede demostrar con este modelo in vitro. Su uso combinado en fórmulas duales facilitaría la actividad del AMC sobre Candida spp actuando como inhibidora o modificadora de las BP mediante la dispersión del EPM
The vaginal mucosa has been widely used for administering antimicrobial agents to treat endogenous infections of the lower genital tract in pregnant and non-pregnant women. Candida spp. elaborates biofilms, and its formation is a complex process requiring that fungal cells establish multiple interactions with the medium. Biofilms are surrounded by an exopolymer matrix that can restrict the activity of antibodies, the diffusion of substances, and be associated with antimicrobials, therefore limiting its actions. General antimicrobials and particular anti-mycotic agents can face difficulties to access the cells within the exopolymer matrix. Many formulas used for empirical treatment have improper combinations with limited or null activity on the biofilms. The presence of molecules that cause its inhibition, thus eliminating the exopolymer matrix inducers, or by other mechanism, will allow the specific antimicrobial activity. Objective: To show that the activity of clindamycin used in dual formula with ketoconazole works on Candida albicans biofilm and on non- albicans species of Candida . Methods: We studied the activity of clindamycin and ketoconazole regarding the adherence and dispersion of biofilms from eight vaginal isolates of C. albicans and 7 of non- albicans Candida . The isolates were inoculated in three tubes with Sabouraud agar and a glass device to form the biofilm according to a known technique. Adherence : Each isolate was incubated for a six-hour period and a combination of clindamycin and ketoconazole from the material of ovules was added and conveniently diluted to one of the tubes of each isolate (62.5/260.4 ug/mL), considering 0 hour. Dispersion: The same dilution was added to another tube after 16 hours. The third tube was used as a control without antimicrobials. The reading was carried out with an optical microscope after 24 hours that the clindamycin and ketoconazole combination had been added and colored with crystal violet. They were then evaluated using photographic programs. The activity of clindamycin (62.5 ug/mL) and ketoconazole (260.4 ug/mL) was analyzed alone with a similar technique. We chose vaginal samples from seven patients with vulvovaginal candidiasis and studied them through the cell layer technique. The clindamycin and ketoconazole combination was used for studying the adherence and dispersion. Results: Adherence: Little influence of clindamycin and ketoconazole was seen in adherence regarding each control. Dispersion: The clindamycin and ketoconazole influence was seen in most of the isolates, especially in those of non- albicans Candida that showed higher presence of exopolymer matrix . The hyphae were only seen in 1 of 15 isolates of Candida spp after the clindamycin and ketoconazole were added at the 16th hour. In biofilms of clinical samples, neither hyphae nor mycotic elements were seen in 5 of 7 compared with the controls. Conclusion: According to these results, the use of a clindamycin and ketoconazole combination in biofilms of Candida spp results in proper penetration of the antimicrobial agent, which is seen by the biofilm dispersion during 24 hours. Clindamycin does not interfere with the action of ketoconazole, but it would promote its anti- Candida activity and would possibly modify surface and EP structures through inhibition of the molecules that facilitate its expression. The in vivo model promotes the immunomodulatory activity that in vitro models do not. Its combined use in dual formulas would facilitate the antimicrobial activity on Candida spp, therefore working as an inhibitor or modifier of the biofilms after dispersion of the exopolymer matrix
Subject(s)
Humans , Female , Candidiasis, Vulvovaginal/microbiology , Clindamycin/pharmacology , Ketoconazole/pharmacology , Reproductive Tract Infections/microbiologyABSTRACT
Objective:To study the effect of caprylic/capric acid glycerides (Lab), propylene glycol (PG) and Azone on the transdermal behavior of ketoconazole and miconazole nitrate in compound ketoconazole gel, to screen appropriate penetration enhanc-ers. Methods:Using a RYJ-6A-type transdermal drug diffusion tester, the effects of Lab, PG and Azone at different concentrations on the transdermal behavior of ketoconazole and miconazole nitrate in compound ketoconazole gel were studied. Results:3% PG showed the most obvious penetration enhancement, which could increase the permeation of ketoconazole by 2. 004 times, and increase the pen-etration of miconazole nitrate by 1. 795 times, and the differences were statistically significant (P<0. 05). Conclusion:The penetra-tion effect of 3% PG is obvious, which can be applied in compound ketoconazole gel.
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Objective:To optimize the preparation technology of ketoconazole and miconazole nitrateβ-cyclodextrin inclusion com-pound. Methods: The weight ratio of β-cyclodextrin to ketoconazole, inclusion temperature and inclusion time as the testing factors, the optimal inclusion technology was screened by orthogonal experiments. Results:The optimum inclusion conditions were as follows:the weight ratio of β-cyclodextrin to ketoconazole was 8 ∶1, the inclusion temperature was 50℃, and the ultrasonic time was 50 min. Conclusion:The optimized β-cyclodextrin inclusion process is simple and convenient to carry out.
ABSTRACT
Paecilomyces lilacinus is a filamentous fungus found in soil and air, which is a rare cause of ocular infection. The majority of case reports involving P. lilacinus among healthy hosts are of endophthalmitis and keratitis. We report a rare case of keratomycosis by P. lilacinus, in an immunocompetent, which responded well to treatment with ketoconazole. Some species belonging to the genus Paecilomyces such as P. lilacinus generally shows a poor response to conventional antifungal drugs. Therefore, correct identification of clinical isolates to the species level is mandatory for the appropriate treatment of the disease.