RESUMEN
A hybrid micelle based mobile phase was used to develop and validate a liquid chromatographic method for the separation and quantification of two local anesthetics namely; lidocaine hydrochloride (LID), and bupivacaine hydrochloride (BPV) in presence of the frequently co administered vasopressors phenyl ephrine (PHR) and ephedrine (EPH). Optimization of chromatographic separation conditions was performed applying experimental one factor at a time tool, and design of experiment, where the retention behavior of all analytes using both optimization protocols was in accordance. Chromatographic separation was carried on a C8 column operating at 40 °C at a flow rate of 1.5 mL/min. using a mobile phase consisting of 0.18 M sodium dodecyl sulphate, 10% acetonitrile, containing 0.3% triethyl amine and adjusted to pH 7 using 2 M ortho phosphoric acid, adopting UV detection at 230 nm. The proposed method was fully validated and applied to both in vitro and in vivo analysis of rat blood samples. The pharmacokinetics of both LID and BPV was followed when they were solitary injected or when co administered with either PHR or EPH. Moreover, the in vitro spiked experiment was also subjected to documented bio-analytical validation procedures.
Asunto(s)
Anestésicos Locales , Cromatografía Liquida/métodos , Monitoreo de Drogas/métodos , Vasoconstrictores , Anestésicos Locales/sangre , Anestésicos Locales/química , Anestésicos Locales/farmacocinética , Animales , Bupivacaína/sangre , Bupivacaína/química , Bupivacaína/farmacocinética , Interacciones Farmacológicas , Efedrina/sangre , Efedrina/química , Efedrina/farmacocinética , Lidocaína/sangre , Lidocaína/química , Lidocaína/farmacocinética , Micelas , Ratas , Vasoconstrictores/sangre , Vasoconstrictores/química , Vasoconstrictores/farmacocinéticaRESUMEN
Stimulants are banned by the World Anti-Doping Agency (WADA) if used "in competition". Being the analysis of stimulants presently carried out on urine samples only, it might be useful, for a better interpretation of analytical data, to discriminate between an early intake of the substance and an administration specifically aimed to improve the sport performance. The purpose of the study was to investigate the differences, in terms of excretion/disappearance of drugs, between urine and oral fluid, a sample that can reflect plasmatic concentrations. Oral fluid and urine samples were collected following oral administration of the following stimulants: modafinil (100 mg), selegiline (10 mg), crotetamide/cropropamide (50 mg each), pentetrazol (100 mg), ephedrine (12 mg), sibutramine (10 mg), mate de coca (a dose containing about 3mg of cocaine); analysis of drugs/metabolites was carried out by gas chromatography/mass spectrometry (GC/MS) in both body fluids. Our results show that both the absolute concentrations and their variation as a function of time, in urine and in oral fluid, are generally markedly different, being the drugs eliminated from urine much more slowly than from oral fluid. Our results also suggest that the analysis of oral fluid could be used to successfully complement the data obtained from urine for "in competition" anti-doping tests; in all those cases in which the metabolite(s) concentration of a substance in urine is very low and the parent compound is not detected, it is indeed impossible, relying on urinary data only, to discriminate between recent administrations of small doses and remote administrations of higher doses.
Asunto(s)
Estimulantes del Sistema Nervioso Central/orina , Doping en los Deportes , Saliva/química , Detección de Abuso de Sustancias/métodos , Adulto , Aminobutiratos/análisis , Aminobutiratos/farmacocinética , Aminobutiratos/orina , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/farmacocinética , Compuestos de Bencidrilo/orina , Calibración , Estimulantes del Sistema Nervioso Central/análisis , Estimulantes del Sistema Nervioso Central/farmacocinética , Cocaína/análisis , Cocaína/farmacocinética , Cocaína/orina , Crotonatos/análisis , Crotonatos/farmacocinética , Crotonatos/orina , Efedrina/análisis , Efedrina/farmacocinética , Efedrina/orina , Femenino , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Modafinilo , Selegilina/análisis , Selegilina/farmacocinética , Selegilina/orina , Factores de TiempoRESUMEN
Three near zero-order controlled-release pseudoephedrine hydrochloride (PEH) formulations demonstrating proportional release rates were developed using 3-Dimensional Printing (3-DP) technology. Mixtures of Kollidon SR and hydroxypropylmethyl cellulose (HPMC) were used as drug carriers. The release rates were adjusted by varying the Kollidon SR-HPMC ratio while keeping fabrication parameters constant. The dosage forms were composed of an immediate release core and a release rate regulating shell, fabricated with an aqueous PEH and an ethanolic triethyl citrate (TEC) binder, respectively. The dosage form design called for the drug to be released via diffusional pathways formed by HPMC in the shell matrix. The release rate was shown to increase correspondingly with the fraction of HPMC contained in the polymer blend. The designed formulations resulted in dosage forms that were insensitive to changes in pH of the dissolution medium, paddle stirring rate, and the presence/absence of a sinker. The near zero-order release properties were unchanged regardless of the dissolution test being performed on either single cubes or on a group of eight cubes encased within a gelatin capsule shell. The chemical and dissolution properties of the three formulations remained unchanged following 1 month's exposure to 25 degrees C/60% RH or 40 degrees C/75% RH environment under open container condition. The in vivo performance of the three formulations was evaluated using a single-dose, randomized, open-label, four-way crossover clinical study composed of 10 fasted healthy volunteers. The pharmacokinetic parameters were analyzed using a noncompartmental model. Qualitative rank order linear correlations between in vivo absorption profiles and in vitro dissolution parameters (with slope and intercept close to unity and origin, respectively) were obtained for all three formulations, indicating good support for a Level A in vivo/in vitro correlation.
Asunto(s)
Efedrina/química , Efedrina/farmacocinética , Metilcelulosa/análogos & derivados , Povidona/química , Tecnología Farmacéutica/instrumentación , Adulto , Área Bajo la Curva , Estudios Cruzados , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Efedrina/administración & dosificación , Calor , Humanos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa , Masculino , Metilcelulosa/química , Solubilidad , Agua/químicaRESUMEN
BACKGROUND: Pheochromocytomas are rare tumors of chromaffin cells for which the optimal management is surgical resection. Precise diagnosis and localization may be elusive. We evaluated whether positron emission tomography (PET) scanning with the combination of [18F]fluorodeoxyglucose (FDG) and the norepinephrine analogue [11C]metahydroxyephedrine (mHED) would allow more exact diagnosis and localization. METHODS: Fourteen patients with suspected pheochromocytoma were evaluated by anatomical imaging (computed tomography or magnetic resonance imaging) and [131I]metaiodobenzylguanidine (MIBG) planar imaging. PET imaging was performed by using mHED with dynamic adrenal imaging, followed by a torso survey and FDG with a torso survey. Images were evaluated qualitatively by an experienced observer. RESULTS: Eight patients had pathology-confirmed pheochromocytoma. Of the other six, two patients had normal adrenal tissue at adrenalectomy, and the other four had subsequent clinical courses inconsistent with a diagnosis of pheochromocytoma. In four of eight patients with pheochromocytoma, MIBG failed to detect one or more sites of pathology-confirmed disease. The mHED-PET detected all sites of confirmed disease, whereas FDG-PET detected all sites of adrenal and abdominal disease, but not bone metastases, in one patient. MIBG and FDG-PET results were all negative in the six patients without pheochromocytoma. One patient with adrenal medullary hyperplasia had a positive mHED-PET scan. PET scanning aided the decision not to operate in three of six patients. The resolution of PET functional imaging was superior to that of MIBG. CONCLUSIONS: PET scanning for pheochromocytoma offers improved quality and resolution over current diagnostic approaches. PET may significantly influence the clinical management of patients with a suspicion of these tumors and warrants further investigation.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Efedrina/análogos & derivados , Fluorodesoxiglucosa F18 , Feocromocitoma/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , 3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales/cirugía , Adulto , Efedrina/farmacocinética , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Feocromocitoma/cirugía , Estudios Prospectivos , Radiofármacos/farmacocinética , Método Simple Ciego , Distribución Tisular , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
UNLABELLED: We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium. METHODS: Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately. RESULTS: After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The regional reduction in sympathetic nerve function was persistent and unaltered for at least 2 mo after the development of hibernating myocardium. CONCLUSION: Hibernating myocardium is associated with persistent reductions in regional uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic innervation in viable dysfunctional myocardium is similar to that occurring after myocardial infarction and may contribute to arrhythmic death in patients with ischemic cardiomyopathy.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico por imagen , Efedrina/análogos & derivados , Aturdimiento Miocárdico/complicaciones , Aturdimiento Miocárdico/diagnóstico por imagen , Sistema Nervioso Simpático/diagnóstico por imagen , Animales , Enfermedades del Sistema Nervioso Autónomo/metabolismo , Ensayos Clínicos como Asunto , Efedrina/farmacocinética , Corazón/diagnóstico por imagen , Corazón/inervación , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Cintigrafía , Radiofármacos/farmacocinética , Porcinos , Sistema Nervioso Simpático/metabolismo , Distribución TisularAsunto(s)
Agonistas alfa-Adrenérgicos/farmacocinética , Efedrina/farmacocinética , Lactancia/efectos de los fármacos , Leche Humana/metabolismo , Agonistas alfa-Adrenérgicos/metabolismo , Adulto , Mama/irrigación sanguínea , Cromatografía Líquida de Alta Presión , Efedrina/metabolismo , Femenino , Humanos , Lactante , Recién Nacido , Lactancia/metabolismo , Leche Humana/química , Prolactina/sangre , Ultrasonografía MamariaRESUMEN
BACKGROUND: It has been demonstrated that ventricular sympathetic reinnervation after cardiac transplantation improves exercise performance. The extent of reinnervation increases with time but is variable. Little is known about other influencing factors. METHODS AND RESULTS: Seventy-seven nonrejecting transplant recipients were cross-sectionally studied by PET with the catecholamine analogue C-11 hydroxyephedrine at 4.8+/-3.5 years after transplantation. Results were compared with history-derived parameters related to recipient's clinical course before, during, and after surgery; donor characteristics; and immunogenetics. Partial reinnervation was observed in 52 patients (extent, 21+/-16% of left ventricle). Complete denervation was found in 25 patients at various times after transplantation. Reinnervation extent correlated with time after surgery (r=0.387; P<0.001) but also inversely with donor age (r=-0.309, P=0.006) and recipient age (r=-0.243, P=0.032). Maximal hydroxyephedrine retention correlated inversely with frequency of rejection episodes (r=-0.267, P=0.019), was reduced when aortic complications occurred perioperatively (9 patients), and correlated inversely with aortic cross-clamp time (r=-0.331, P=0.006). Other parameters were not associated with reinnervation. Patients were surveyed for clinical complications over >12 months after PET (until 7.3+/-4.2 years after transplantation), but significant effects of reinnervation on outcome were not observed. CONCLUSIONS: The present data suggest that sympathetic reinnervation after cardiac transplantation is not simply a function of time. Reinnervation is more likely with young age, fast and uncomplicated surgery, and low rejection frequency. Despite few effects on prognosis in otherwise healthy recipients, improved understanding of clinical determinants may contribute to enhance allograft reinnervation and thereby augment exercise capacity in the future.
Asunto(s)
Efedrina/análogos & derivados , Trasplante de Corazón , Ventrículos Cardíacos/inervación , Regeneración Nerviosa/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Factores de Edad , Radioisótopos de Carbono , Medios de Contraste/farmacocinética , Estudios Transversales , Supervivencia sin Enfermedad , Efedrina/farmacocinética , Femenino , Estudios de Seguimiento , Trasplante de Corazón/inmunología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Regeneración Nerviosa/inmunología , Análisis de Regresión , Factores Sexuales , Tasa de Supervivencia , Sistema Nervioso Simpático/crecimiento & desarrollo , Tomografía Computarizada de Emisión , Tolerancia al Trasplante/inmunología , Función VentricularRESUMEN
Os autores fazem uma revisäo das "drogas desenhadas" - específicamente o MDMA, a metcatinona e o alfa-metil-fentanil, substâncias sintéticas produzidas ilegalmente em laboratório; enfatizam suas propriedades, seu uso crescente na populaçäo e a importância do diagnóstico de manifestaçöes pelo uso dessas drogas
Asunto(s)
Humanos , Masculino , Femenino , 3,4-Metilenodioxianfetamina/efectos adversos , 3,4-Metilenodioxianfetamina/farmacocinética , Drogas Ilícitas/efectos adversos , Drogas Ilícitas/farmacocinética , Efedrina/efectos adversos , Efedrina/farmacocinética , Trastornos Relacionados con SustanciasRESUMEN
BACKGROUND: Regional cardiac sympathetic hyperactivity predisposes to malignant arrhythmias in nondiabetic cardiac disease. Conversely, however, cardiac sympathetic denervation predicts increased morbidity and mortality in severe diabetic autonomic neuropathy (DAN). To unite these divergent observations, we propose that in diabetes regional cardiac denervation may elsewhere induce regional sympathetic hyperactivity, which may in turn act as a focus for chemical and electrical instability. Therefore, the aim of this study was to explore regional changes in sympathetic neuronal density and tone in diabetic patients with and without DAN. METHODS AND RESULTS: PET using the sympathetic neurotransmitter analogue 11C-labeled hydroxyephedrine ([11C]-HED) was used to characterize left ventricular sympathetic innervation in diabetic patients by assessing regional disturbances in myocardial tracer retention and washout. The subject groups comprised 10 diabetic subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic subjects with severe DAN, and 10 healthy subjects. Abnormalities of cardiac [11C]-HED retention were detected in 40% of DAN-free diabetic subjects. In subjects with mild neuropathy, tracer defects were observed only in the distal inferior wall of the left ventricle, whereas with more severe neuropathy, defects extended to involve the distal and proximal anterolateral and inferior walls. Absolute [11C]-HED retention was found to be increased by 33% (P<0.01) in the proximal segments of the severe DAN subjects compared with the same regions in the DAN-free subjects (30%; P<0.01 greater than the proximal segments of the mild DAN subjects). Despite the increased tracer retention, no appreciable washout of tracer was observed in the proximal segments, consistent with normal regional tone but increased sympathetic innervation. Distally, [11C]-HED retention was decreased in severe DAN by 33% (P<0.01) compared with the DAN-free diabetic subjects (21%; P<0.05 lower than the distal segments of the mild DAN subjects). CONCLUSIONS: Diabetes may result in left ventricular sympathetic dysinnervation with proximal hyperinnervation complicating distal denervation. This combination could result in potentially life-threatening myocardial electrical instability and explain the enhanced cardioprotection from beta-blockade in these subjects.
Asunto(s)
Neuropatías Diabéticas/fisiopatología , Corazón/inervación , Sistema Nervioso Simpático/diagnóstico por imagen , Sistema Nervioso Simpático/fisiopatología , Adulto , Análisis de Varianza , Radioisótopos de Carbono/farmacocinética , Desnervación , Neuropatías Diabéticas/diagnóstico por imagen , Neuropatías Diabéticas/mortalidad , Efedrina/análogos & derivados , Efedrina/farmacocinética , Femenino , Corazón/diagnóstico por imagen , Frecuencia Cardíaca , Ventrículos Cardíacos/inervación , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Neuronas/diagnóstico por imagen , Neuronas/fisiología , Valores de Referencia , Tomografía Computarizada de Emisión , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals. When HED is labeled with 11C, its distribution can be mapped in vivo using PET. The purposes of this investigation were to characterize the uptake of 11C-HED in pheochromocytoma and to determine the feasibility and advantages of utilizing this compound as a tumor imaging agent. Ten patients with known or suspected pheochromocytoma were studied. Each patient underwent PET scanning with 11C-HED and conventional scintigraphy with MIBG. Pheochromocytomas were localized by PET scanning in 9 of the 10 patients. Image quality was excellent and superior to that obtained from planar and tomographic MIBG studies. The uptake of 11C-HED into pheochromocytomas was rapid; tumors were evident within 5 min following intravenous injection. All lesions within the field of view that were identified by MIBG scintigraphy were readily apparent. PET scanning with 11C-HED localizes pheochromocytoma using a specifically designed radiotracer and advanced imaging technology. The method has promise for locating the more elusive tumors.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Efedrina/análogos & derivados , Feocromocitoma/diagnóstico por imagen , Tomografía Computarizada de Emisión , 3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales/metabolismo , Adulto , Anciano , Radioisótopos de Carbono , Efedrina/farmacocinética , Femenino , Humanos , Radioisótopos de Yodo , Yodobencenos , Masculino , Persona de Mediana Edad , Feocromocitoma/metabolismoRESUMEN
La realización de la anestesia en obstetricia se diferencia de otras, fundamentalmente porque son dos los seres humanos que están a nuestro cuidado, unidos a través de la placenta. La adecuada elección de las drogas debe basarse en la fisiología de la embarazada, de la placenta y del feto. La presente revisión considera estos tópicos conjuntamente con los factores fisiopatológicos que alteran la farmacocinética de los fármacos utilizados en este período. Combinando ambos conceptos, la fisiología y la farmacocinética alteradas, nos permite inferir el uso racional de medicamentos en el binomio madre-feto, ya sea durante el trabajo de parto, el parto en sí, y en las intervenciones no obstétricas y obstétricas. Los grupos de drogas consideradas son dos : drogas anestésicas y perianestésicas. En el primer grupo se menciona los agentes inductores, ansiolíticos, neurolépticos, morfinosímiles, relajantes musculares periféricos, agentes inhalatorios y anestésicos locales. En el segundo grupo se ha tratado bloqueantes H2, bloqueantes colinérgicos, hipertensores, ocitócicos y depresores del miometrio.