RESUMEN
During the past years transcatheter aortic valve implantation (TAVI) has evolved to a standard technique for the treatment of high risk patients suffering from severe aortic stenosis. Worldwide the number of TAVI procedures is increasing exponentially. In this context both the transapical antegrade (TA) and the transfemoral retrograde (TF) approach are predominantly used and can be considered as safe and reproducible access sites for TAVI interventions. As a new technology TAVI is in a constant progress regarding the development of new devices. While in the first years only the Edwards SAPIEN(TM) and the Medtronic CoreValve(TM) prostheses were commercial available, recently additional devices obtained CE-mark approval and others have entered initial clinical trials. In addition to enhance the treatment options in general, the main driving factor to further develop new device iterations is to solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full repositionability.
Asunto(s)
Válvula Aórtica/cirugía , Cateterismo Cardíaco/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Estenosis de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/terapia , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/tendencias , Humanos , Resultado del TratamientoRESUMEN
During the past years TAVI has evolved to a standard technique for the treatment of high risk patients suffering from severe aortic stenosis. Worldwide the number of TAVI procedures is increasing exponentially. In this context both the transapical antegrade (TA) and the transfemoral retrograde (TF) approach are predominantly used and can be considered as safe and reproducible access sites for TAVI interventions. As a new technology TAVI is in a constant progress regarding the development of new devices. While in the first years only the Edwards SAPIEN™ and the Medtronic CoreValve™ prostheses were commercial available, recently additional devices obtained CE-mark approval and others have entered initial clinical trials. In addition to enhance the treatment options in general, the main driving factor to further develop new device iterations is to solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full repositionability.
Asunto(s)
Insuficiencia de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/terapia , Cateterismo Cardíaco/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Prótesis Valvulares Cardíacas , Falla de Prótesis , Anciano de 80 o más Años , Insuficiencia de la Válvula Aórtica/diagnóstico , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico , Cateterismo Cardíaco/efectos adversos , Remoción de Dispositivos , Ecocardiografía Doppler en Color , Ecocardiografía Transesofágica , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Diseño de Prótesis , Retratamiento , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Anciano , Estenosis de la Válvula Aórtica/patología , Cateterismo Cardíaco/métodos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Humanos , MasculinoRESUMEN
A sensitive, rapid and selective liquid chromatography negative electrospray ionization tandem mass spectrometry [LC-(-)ESI-MS-MS] method has been developed and validated for the simultaneous quantification of budesonide (BUD) and its major metabolites, 6beta-hydroxybudesonide (OH-BUD) and 16alpha-hydroxyprednisolone (OH-PRED) in human plasma. The method was validated over a linear range from 0.1 to 10 ng/mL for all three analytes using a solid-phase extraction procedure with 9-fluoro-hydrocortisone as the internal standard. The between-day and within-day coefficients of variation for all compounds were < or =20% at the concentrations of lower limit of quantification and < or =15% at other quality control concentrations. The utility of this assay was demonstrated by monitoring BUD, OH-BUD and OH-PRED plasma concentrations in one healthy subject for 24 h following a 3 mg oral dose of budesonide, administered as a pH modified release capsule (Budenofalk) to healthy volunteers.
Asunto(s)
Budesonida/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Humanos , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A radioimmunoassay is described that measures budesonide in plasma after solid-phase extraction (SPE/RIA) of the analyte. The performance of the assay was compared with that of a selective LC/MS method. The limit of quantitation of budesonide determined for the LC/MS and SPE/RIA assay was 50 pg/mL and 120 pg/mL, respectively. Based on quality control samples, a higher variability was observed for the SPE/RIA (CV between 4.5 and 23.0%) than for the LC/MS method (CV between 7.5 and 12.5%). Plasma samples obtained from healthy volunteers after administration of budesonide rectal foam were assayed by both methods. In a subset of samples, these results were compared with those measured by direct RIA to evaluate the selectivity of two assays. About two times higher budesonide levels were measured with the direct RIA (lacking the extraction step), presumably because of cross-reactivity with budesonide metabolites, indicating that the extraction step in SPE/RIA is necessary for selectivity. Both SPE/RIA and LC/MS methods were found to be selective, sensitive and suitable for pharmacokinetic studies. Results obtained from the two methods were compared with a number of statistical methods. Ratios of results obtained for the clinical samples were close to 1 (ratio LC-MS/ SPE/RIA = 0.98 +/- 0.27). Linear regression indicated a slope of 1.17 +/- 0.0378. The concordance correlation (r = 0.91) indicated that the agreement between both methods was fair while the Bland-Altman plot indicated that the agreement was less pronounced at higher concentrations (1-3 ng/mL). In summary, the results confirm that the SPE/RIA is an alternative to HPLC/MS and that among the statistical methods tested the concordance correlation analysis was judged to be the most informative test to assess the comparability of two methods.
Asunto(s)
Broncodilatadores/sangre , Budesonida/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Radioinmunoensayo/métodos , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadAsunto(s)
Hidrocortisona/sangre , Prednisolona/análogos & derivados , Administración Cutánea , Administración por Inhalación , Administración Oral , Adulto , Disponibilidad Biológica , Biotransformación , Emulsiones , Semivida , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Apósitos Oclusivos , Pomadas , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Prednisolona/administración & dosificación , Prednisolona/sangre , Prednisolona/farmacocinética , Prednisolona/farmacologíaRESUMEN
The relative binding affinities (RBA) of two locally used glucocorticoids, rimexolone and flunisolide have been measured for the glucocorticoid receptor of human synovial tissue. The non-fluorinated derivative rimexolone exhibited a binding affinity (RBA of 130) somewhat higher than that of dexamethasone (RBA of 100) but lower than that of flunisolide (RBA 190). Potential metabolites of rimexolone hydroxolated at the C17 side-chain, showed decreased binding affinities, while the 6-hydroxy metabolite of rimexolone and flunisolide (its main metabolite) and the 4,5-dihydro metabolites of rimexolone hardly bound at all. These results support previous pharmacological findings that the high ratio of local to systemic effects of both compounds are due to a pronounced receptor affinity of the parent compounds and the fast systemic metabolism to derivatives with low pharmacodynamic activity.