RESUMEN
Background: Randomized controlled trial to evaluate synergy between taxane plus platinum chemotherapy and CADI-05, a Toll like receptor-2 agonist targeting desmocollin-3 as a first-line therapy in advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients with advanced NSCLC (stage IIIB or IV) were randomized to cisplatin-paclitaxel (chemotherapy group, N = 112) or cisplatin-paclitaxel plus CADI-05 (chemoimmunotherapy group, N = 109). CADI-05 was administered a week before chemotherapy and on days 8 and 15 of each cycle and every month subsequently for 12 months or disease progression. Overall survival was compared using a log-rank test. Computed tomography was carried out at baseline, end of two cycles and four cycles. Response rate was evaluated using Response Evaluation Criteria in Solid Tumors criteria by an independent radiologist. Results: As per intention-to-treat analysis, no survival benefit was observed between two groups [208 versus 196 days; hazard ratio, 0.86; 95% confidence interval (CI) 0.63-1.19; P = 0.3804]. In a subgroup analysis, improvement in median survival by 127 days was observed in squamous NSCC with chemoimmunotherapy (hazard ratio, 0.55; 95% CI 0.32-0.95; P = 0.046). In patients receiving planned four cycles of chemotherapy, there was improved median overall survival by 66 days (299 versus 233 days; hazard ratio, 0.64; 95% CI 0.41 to 0.98; P = 0.04) in the chemoimmunotherapy group compared with the chemotherapy group. This was associated with the improved survival by 17.48% at the end of 1 year, in the chemoimmunotherapy group. Systemic adverse events were identical in both the groups. Conclusion: There was no survival benefit with the addition of CADI-05 to the combination of cisplatin-paclitaxel in patients with advanced NSCLC; however, the squamous cell subset did demonstrate a survival advantage.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Vacunas Bacterianas/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Desmocolinas/antagonistas & inhibidores , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Modelos de Riesgos Proporcionales , Receptor Toll-Like 2/agonistas , Resultado del TratamientoRESUMEN
A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 +/- 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.
Asunto(s)
Antagonistas Adrenérgicos beta/sangre , Celiprolol/sangre , Celiprolol/farmacocinética , Cromatografía en Capa Delgada , HumanosRESUMEN
A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method has been developed for the measurement of sparfloxacin in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting sparfloxacin from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Sparfloxacin was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.1 to 0.8 microgram ml-1 was 94.9 +/- 0.98% and the lowest amount of sparfloxacin that could be detected was 50 ng ml-1 plasma. The method provides a direct estimate of the amount of sparfloxacin present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of sparfloxacin after oral administration of two marketed preparations to healthy volunteers.
Asunto(s)
Antiinfecciosos/sangre , Antituberculosos/sangre , Cromatografía Líquida de Alta Presión/métodos , Fluoroquinolonas , Quinolonas/sangre , Administración Oral , Adulto , Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacocinética , Antituberculosos/administración & dosificación , Antituberculosos/farmacocinética , Área Bajo la Curva , Disponibilidad Biológica , Humanos , Masculino , Quinolonas/administración & dosificación , Quinolonas/farmacocinéticaRESUMEN
A rapid and sensitive high-performance thin-layer chromatographic assay has been developed for the measurement of nimesulide in human plasma. Its use for pharmacokinetic studies has been evaluated. The method includes a single-stage extraction procedure without the use of an internal standard. Analysis was performed on plasma containing known amounts of the drug, on drug-free plasma, and on plasma containing an unknown quantity of the drug. Known amounts of extract and nimesulide (100 and 200 ng, as external standard) were spotted on precoated silica-gel 60F254 plates by means of a Camag Linomat IV autosampler. Quantification was achieved using a Camag TLC scanner 3. The recovery of the method was 97.10 +/- 2.22%. The method was applied for the determination of plasma levels and pharmacokinetic parameters of nimesulide after oral administration of two formulations (100 mg) in healthy volunteers. The method is a sensitive, economical, rapid and specific assay for nimesulide in human plasma, and is suitable for pharmacokinetic studies after therapeutic doses.
Asunto(s)
Antiinflamatorios no Esteroideos/sangre , Sulfonamidas/sangre , Administración Oral , Adulto , Antiinflamatorios no Esteroideos/farmacocinética , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Estudios Cruzados , Humanos , Masculino , Sensibilidad y Especificidad , Sulfonamidas/farmacocinética , ComprimidosRESUMEN
A rapid and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the measurement of lansoprazole in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting lansoprazole from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Lansoprazole was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.05 to 0.25 microg/ml was 95.37+/-2.15% and the lowest amount of lansoprazole that could be detected was 20 ng/ml plasma. The method provides a direct estimate of the amount of lansoprazole present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of lansoprazole after oral administration of two marketed preparations to healthy volunteers.
Asunto(s)
Antiulcerosos/sangre , Inhibidores Enzimáticos/sangre , Omeprazol/análogos & derivados , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacocinética , Cromatografía en Capa Delgada , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacocinética , Humanos , Lansoprazol , Masculino , Omeprazol/administración & dosificación , Omeprazol/sangre , Omeprazol/farmacocinética , Comprimidos RecubiertosRESUMEN
A rapid and sensitive high-performance thin-layer chromatography (HPTLC) assay has been developed for the measurement of cetirizine in human plasma and its utility for pharmacokinetic study has been evaluated. In the proposed HPTLC method, protein-bound cetirizine was freed by proteolysis of plasma proteins by incubating the plasma with 0.35% pepsin and then extracting with 2 mL pH 5.0 phosphate buffer, followed by 4 mL chilled chloroform. The chloroform layer was separated and concentrated. An aliquot of the extract was then spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Quantification was with the help of a dual-wavelength TLC scanner. The proposed method had a recovery of 98% and the lowest amount of cetirizine that could be detected was 50 ng. The method was applied for the determination of the plasma levels and pharmacokinetic parameters of cetirizine after oral administration of two marketed preparations in healthy volunteers and the pharmacokinetic parameters determined by the proposed method were in agreement with previously reported values.
Asunto(s)
Cetirizina/sangre , Antagonistas de los Receptores Histamínicos H1/sangre , Adulto , Disponibilidad Biológica , Cetirizina/farmacocinética , Cromatografía Líquida de Alta Presión , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Humanos , Persona de Mediana EdadRESUMEN
A high-performance thin-layer chromatographic procedure has been developed for the determination of ranitidine, a H2-receptor antagonist, in plasma. The detection and quantification were performed without using internal standards. A single-stage extraction procedure was followed for extracting ranitidine from plasma, and a known amount of the extract was spotted on precoated silica gel F254 plates. Ranitidine was quantified using a Shimadzu CS930 dual-wavelength TLC scanner. The method provides a direct estimate of total ranitidine present in the plasma.
Asunto(s)
Antagonistas de los Receptores H2 de la Histamina/sangre , Ranitidina/sangre , Adulto , Disponibilidad Biológica , Calibración , Cromatografía en Capa Delgada , Semivida , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/farmacocinética , Humanos , Indicadores y Reactivos , Masculino , Ranitidina/administración & dosificación , Ranitidina/farmacocinética , Estándares de ReferenciaRESUMEN
A novel analytical method for determination of the total plasma levels (free and protein bound) of the calcium channel blocking agent amlodipine has been developed using a high-performance thin-layer chromatographic (HPTLC) procedure. Detection and quantitation were performed without internal standards. In previously described methods for the estimation of amlodipine by gas chromatography and high-performance liquid chromatography, only the free levels in plasma and serum were quantified at 7% of the total amlodipine level, with the remaining 93% bound to plasma protein and tissue. The present method employs proteolysis of the plasma proteins by incubating plasma for 2 h in pepsin solution. After proteolysis amlodipine is extracted and a known amount of the extract is spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Amlodipine was quantified using a dual-wavelength TLC scanner. The method provides a direct estimate of the total amlodipine present in plasma.
Asunto(s)
Amlodipino/sangre , Amlodipino/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Amlodipino/administración & dosificación , Humanos , Pepsina A , Sensibilidad y EspecificidadRESUMEN
Two populations of Escherichia coli, each initiated with a single clone containing a derivative of the plasmid pBR322, were maintained for long periods in glucose-limited continuous culture. In both populations, after an extensive number of generations had elapsed, clones were isolated in which the transposon Tn3 from the plasmid had integrated into the bacterial chromosome. In both cases examined, the transpositions were shown to increase relative fitness approximately 6-7%, in the environment in which the populations were maintained. The loci of integration were mapped to approximately 13.2 min (population 1) and approximately 32.8 min (population 2).
Asunto(s)
Escherichia coli/genética , Evolución Biológica , Mapeo Cromosómico , Cromosomas Bacterianos , Elementos Transponibles de ADN , ADN Bacteriano/genética , Plásmidos , Transducción GenéticaRESUMEN
Under conditions where plasmid-carriage is deleterious to the cell, evolutionary changes may be expected which result in an attenuation of the deleterious effect of the plasmid. During long-term growth in glucose-limited continuous culture, initiated with a single clone of Escherichia coli containing a derivative of the plasmid pBR322, a structural change arose in the plasmid and predominated in the plasmid-containing sector of the population. This variant possessed a 2.25 kb deletion encompassing the tetracycline resistance operon as well as a region of about 1.5 kb upstream from this operon. Competition experiments involving strains carrying the plasmid with the spontaneous deletion, and strains carrying plasmids with artificially constructed deletions, revealed that deletion of this region of the plasmid, involving loss of tetracycline resistance, resulted in an increment in fitness of between 10 and 20%. From the magnitude of the growth advantage, we conclude that the attenuation of the deleterious effect of the plasmid was mainly due to a reduction in the plasmid mediated interference in the metabolism of the cell caused by a deletion of the tetracycline resistance gene.