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2.
Isr Med Assoc J ; 22(2): 83-88, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32043324

RESUMEN

BACKGROUND: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting. OBJECTIVES: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer's guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds. METHODS: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement. RESULTS: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer's guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds. CONCLUSIONS: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.


Asunto(s)
Bromelaínas/administración & dosificación , Quemaduras , Terapia Enzimática/métodos , Cicatrización de Heridas/efectos de los fármacos , Heridas y Traumatismos , Administración Tópica , Adulto , Quemaduras/diagnóstico , Quemaduras/terapia , Monitoreo de Drogas/métodos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Tiempo de Tratamiento , Índices de Gravedad del Trauma , Resultado del Tratamiento , Heridas y Traumatismos/diagnóstico , Heridas y Traumatismos/terapia
3.
Artículo en Inglés | MEDLINE | ID: mdl-31915109

RESUMEN

An liquid chromatography-mass spectrometry (LC-MS/MS) assay was developed for the combined analysis of the five poly (ADP-ribose) polymerase (PARP) inhibitors niraparib, olaparib, rucaparib talazoparib and veliparib. A simple and fast sample pre-treatment method was used by protein precipitating of plasma samples with acetonitrile and dilution of the supernatant with formic acid (0.1% v/v in water). This was followed by chromatographic separation on a reversed-phase UPLC BEH C18 column and detection with a triple quadrupole mass spectrometer operating in the positive mode. A simplified validation procedure specifically designed for bioanalytical methods for clinical therapeutic drug monitoring (TDM) purposes, was applied. This included assessment of the calibration model, accuracy and precision, lower limit of quantification (LLOQ), specificity and selectivity, carry-over and stability. The validated range was 30-3000 ng/mL for niraparib, 100-10,000 ng/mL for olaparib, 50-5000 ng/mL for rucaparib, 0.5-50 ng/mL for talazoparib and 50-5000 for veliparib. All results were within the criteria of the US Food and Drug Administration (FDA) guidance and European Medicines Agency (EMA) guidelines on method validation. The assay has been successfully implemented in our laboratory.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Monitoreo de Drogas/métodos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/sangre , Espectrometría de Masas en Tándem/métodos , Bencimidazoles/sangre , Cromatografía de Fase Inversa/métodos , Compuestos Heterocíclicos con 1 Anillo/sangre , Humanos , Indoles/sangre , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados
4.
Artículo en Inglés | MEDLINE | ID: mdl-31931326

RESUMEN

Cabozantinib is a novel multi-target tyrosine kinase inhibitor recently approved in metastatic renal cell carcinoma (mRCC) leading to frequent severe toxicities requiring empirical dose reduction. Therapeutic drug monitoring (TDM) could help to predict the risk for severe toxicities by quickly detecting overexposed patients followed by prospective adaptive dosing strategy. To achieve this goal, a simple and rapid assay to monitor cabozantinib plasma concentration was developed and validated. After a single precipitation step with 87% recovery, cabozantinib was assayed by liquid chromatography tandem mass spectrometry (electrospray ionization interface) over a 25-5000 ng/ml range covering usual plasma levels in clinical setting. For cabozantinib and cabozantinib 2H4 used as internal standard, quantification was performed using the m/z 502 â†’ m/z 323 and m/z 506 â†’ m/z 323 transitions, respectively. Analytical runtime was 5 min. Both inter-days and intra-day accuracy and precision were <15%. When tested in routine clinical practice in a subset of mRCC patients treated with standard 60 mg quaque die (QD) dosing, the method proved to be fully adapted and neither analytical interferences nor matrix effect was observed. Results showed that cabozantinib trough levels were highly variable among patients (i.e., 973 ± 501 ng/ml, CV = 52%), calling for implementing TDM in patients with mRCC to monitor exposure levels and evaluate concentration-response relationship.


Asunto(s)
Anilidas/sangre , Antineoplásicos/sangre , Cromatografía Liquida/métodos , Monitoreo de Drogas/métodos , Espectrometría de Masas/métodos , Piridinas/sangre , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/tratamiento farmacológico , Modelos Lineales , Piridinas/uso terapéutico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
5.
Mayo Clin Proc ; 95(1): 90-100, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31902433

RESUMEN

OBJECTIVE: To compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage. PATIENTS AND METHODS: This retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m2. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome. RESULTS: The cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes. CONCLUSION: Sulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Metformina , Insuficiencia Renal Crónica , Compuestos de Sulfonilurea , Canadá/epidemiología , Enfermedades Cardiovasculares/epidemiología , Creatinina/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Monitoreo de Drogas/métodos , Monitoreo de Drogas/estadística & datos numéricos , Modificador del Efecto Epidemiológico , Femenino , Tasa de Filtración Glomerular , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Metformina/administración & dosificación , Metformina/efectos adversos , Persona de Mediana Edad , Mortalidad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos
7.
J Clin Psychiatry ; 81(2)2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31995677

RESUMEN

OBJECTIVE: A nominal group process followed by a modified Delphi method was used to survey expert opinions on best practices for tardive dyskinesia (TD) screening, diagnosis, and treatment and to identify areas lacking in clinical evidence. PARTICIPANTS: A steering committee of 11 TD experts met in nominal group format to prioritize questions to be addressed and identify core bibliographic materials and criteria for survey panelists. Of 60 invited experts, 29 (23 psychiatrists and 6 neurologists) agreed to participate. EVIDENCE: A targeted literature search of PubMed (search term: tardive dyskinesia) and recommendations of the steering committee were used to generate core bibliographic material. Inclusion criteria were as follows: (1) review articles, meta-analyses, guidelines, or clinical trials; (2) publication in English between 2007 and 2017; (3) > 3 pages in length; and (4) publication in key clinical journals with impact factors ≥ 2.0. Of 29 references that met these criteria, 18 achieved a score ≥ 5 (calculated as the number of steering committee votes multiplied by journal impact factor and number of citations divided by years since publication) and were included. CONSENSUS PROCESS: Two survey rounds were conducted anonymously through electronic media from November 2017 to January 2018; responses were collected, collated, and analyzed. Respondent agreement was defined a priori as unanimous (100%), consensus (75%-99%), or majority (50%-74%). For questions using a 5-point Likert scale, agreement was based on percentage of respondents choosing ≥ 4 ("agree completely" or "agree"). Round 1 survey included questions on TD screening, diagnosis, and treatment. Round 2 questions were refined per panelist feedback and excluded Round 1 questions with < 25% agreement and > 75% agreement (unless feedback suggested further investigation). CONCLUSIONS: Consensus was reached that (1) a brief, clinical assessment for TD should be performed at every clinical encounter in patients taking antipsychotics; (2) even mild movements in 1 body area may represent possible TD; (3) management requires an overall evaluation of treatment, including reassessment of antipsychotics and anticholinergics as well as consideration of vesicular monoamine transporter 2 (VMAT2) inhibitors; and (4) informed discussions with patients/caregivers are essential.


Asunto(s)
Antipsicóticos , Antagonistas Colinérgicos , Tamizaje Masivo/métodos , Administración del Tratamiento Farmacológico/normas , Examen Neurológico/métodos , Discinesia Tardía , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/efectos adversos , Consenso , Técnica Delfos , Monitoreo de Drogas/métodos , Monitoreo de Drogas/normas , Humanos , Guías de Práctica Clínica como Asunto , Medición de Riesgo/métodos , Discinesia Tardía/inducido químicamente , Discinesia Tardía/diagnóstico , Discinesia Tardía/terapia , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores
8.
J Clin Psychiatry ; 81(2)2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31995679

RESUMEN

Valbenazine and deutetrabenazine are FDA-approved as treatment for tardive dyskinesia (TD). Both medications are vesicular monoamine transporter type 2 (VMAT2) inhibitors, and both are effective for reducing TD symptoms. Clinicians need to be aware of the adverse effects of valbenazine and deutetrabenazine, as well as other key differences between the two, in order to individualize treatment. Using the Abnormal Involuntary Movement Scale assists clinicians in assessing progress for each patient. Treating TD effectively with these new medications will reduce the burden of the condition for patients.


Asunto(s)
Examen Neurológico/métodos , Discinesia Tardía , Tetrabenazina/análogos & derivados , Valina/análogos & derivados , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Monitoreo de Drogas/métodos , Humanos , Administración del Tratamiento Farmacológico , Moduladores del Transporte de Membrana/administración & dosificación , Moduladores del Transporte de Membrana/efectos adversos , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/normas , Psiquiatría/educación , Discinesia Tardía/inducido químicamente , Discinesia Tardía/diagnóstico , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/administración & dosificación , Tetrabenazina/efectos adversos , Resultado del Tratamiento , Valina/administración & dosificación , Valina/efectos adversos
10.
Anal Bioanal Chem ; 412(4): 1011-1024, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897563

RESUMEN

Cabbage flower-like Ho3+/NiO nanostructure (CFL-Ho3+/NiO NSs) with significant electrocatalytic oxidation has been published for the first time. First, structure and morphology of CFL-Ho3+/NiO-NSs have been described by XRD, SEM, and EDX methods. Then, CFL-Ho3+/NiO-NSs have been applied as a modifier for simultaneous electrochemical detection of methotrexate (MTX) and carbamazepine (CBZ). Functions of the modified electrode have been dealt with through electrochemical impedance spectroscopy (EIS). It has been demonstrated that the electrode response has been linear from 0.001-310.0 µM with a limit of detection of 5.2 nM and 4.5 nM (3 s/m) through DPV for MTX and CBZ. Diffusion coefficient (D) and heterogeneous rate constant (kh) have been detected for MTX and CBZ oxidation at the surface of the modified electrode. Moreover, CFL-Ho3+/NiO-NS/GCE has been employed for determining MTX and CBZ in urine and drug specimens. Outputs showed the analyte acceptable recovery. Therefore, the electrode could be applied to analyze both analytes in drug prescription and clinical laboratories. Graphical abstract Electrochemical sensor based on bifunctional cabbage flower-like Ho3+/NiO nanostructures modified glassy carbon electrode for simultaneous detecting methotrexate and carbamazepine was fabricated.


Asunto(s)
Analgésicos no Narcóticos/farmacocinética , Carbamazepina/farmacocinética , Monitoreo de Drogas/métodos , Inmunosupresores/farmacocinética , Metotrexato/farmacocinética , Analgésicos no Narcóticos/análisis , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/orina , Carbamazepina/análisis , Carbamazepina/sangre , Carbamazepina/orina , Técnicas Electroquímicas/métodos , Holmio/química , Humanos , Inmunosupresores/análisis , Inmunosupresores/sangre , Inmunosupresores/orina , Límite de Detección , Metotrexato/análisis , Metotrexato/sangre , Metotrexato/orina , Nanoestructuras/química , Níquel/química , Oxidación-Reducción , Comprimidos
11.
Biochim Biophys Acta Rev Cancer ; 1873(1): 188319, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31678141

RESUMEN

The treatment of cancer is still a major challenge. But tremendous progress in anticancer drug discovery and development has occurred in the last few decades. However, this progress has resulted in few effective oncology products due to challenges associated with anticancer drug delivery. Oral administration is the most preferred route for anticancer drug delivery, but the majority of anticancer drugs currently in product pipelines and the majority of those that have been commercially approved have inherently poor water solubility, and this cannot be mitigated without compromising their potency and stability. The poor water solubility of anticancer drugs, in conjunction with other factors, leads to suboptimal pharmacokinetic performance. Thus, these drugs have limited efficacy and safety when administered orally. The amorphous solid dispersion (ASD) is a promising formulation technology that primarily enhances the aqueous solubility of poorly water-soluble drugs. In this review, we discuss the challenges associated with the oral administration of anticancer drugs and the use of ASD technology in alleviating these challenges. We emphasize the ability of ASDs to improve not only the pharmacokinetics of poorly water-soluble anticancer drugs, but also their efficacy and safety. The goal of this paper is to rationalize the application of ASD technology in the formulation of anticancer drugs, thereby creating superior oncology products that lead to improved therapeutic outcomes.


Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Monitoreo de Drogas/métodos , Tecnología Farmacéutica/métodos , Administración Oral , Antineoplásicos/química , Antineoplásicos/farmacocinética , Química Farmacéutica , Sistemas de Liberación de Medicamentos/tendencias , Descubrimiento de Drogas/métodos , Descubrimiento de Drogas/tendencias , Monitoreo de Drogas/tendencias , Humanos , Solubilidad , Tecnología Farmacéutica/tendencias , Agua/química
12.
Expert Opin Drug Saf ; 19(1): 43-57, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31770500

RESUMEN

Introduction: Clozapine remains the most effective antipsychotic for treatment-refractory schizophrenia. However, ~40% of the patients respond insufficiently to clozapine. Clozapine's effects, both beneficial and adverse, have been proposed to be partially attributable to its main metabolite, N-desmethylclozapine (NDMC). However, the relation of the clozapine to norclozapine ratio (CLZ:NDMC; optimally defined as ~2) to clinical response and metabolic outcomes is not clear.Areas covered: This narrative review comprehensively examines the clinical utility of the CLZ:NDMC ratio to reduce metabolic risk and increase treatment efficacy. The association of the CLZ:NDMC ratio with changes in psychopathology, cognitive functioning, and cardiometabolic burden will be explored, as well as adjunctive treatments and their effects.Expert opinion: The literature suggests a positive association between the CLZ:NDMC ratio and better cardiometabolic outcomes. Conversely, the CLZ:NDMC ratio appears inversely associated with better cognitive functioning but less consistently with other psychiatric domains. The CLZ:NDMC ratio may be useful for predicting and monitoring cardiometabolic adverse effects and optimizing potential cognitive benefits of clozapine. Future studies are required to replicate these findings, which if substantiated, would encourage examination of adjunctive treatments aiming to alter the CLZ:NDMC ratio to best meet the needs of the individual patient, thereby broadening clozapine's clinical utility.


Asunto(s)
Antipsicóticos/administración & dosificación , Clozapina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/efectos adversos , Antipsicóticos/farmacocinética , Clozapina/efectos adversos , Clozapina/análogos & derivados , Clozapina/sangre , Clozapina/farmacocinética , Cognición/efectos de los fármacos , Monitoreo de Drogas/métodos , Humanos
13.
J Chromatogr Sci ; 57(10): 892-900, 2020 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-31609432

RESUMEN

Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug-drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.


Asunto(s)
Antineoplásicos , Capecitabina , Cromatografía Líquida de Alta Presión/métodos , Neoplasias Colorrectales/tratamiento farmacológico , Monitoreo de Drogas/métodos , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Capecitabina/sangre , Capecitabina/farmacocinética , Capecitabina/uso terapéutico , Cromatografía en Capa Delgada , Interacciones de Drogas , Estabilidad de Medicamentos , Humanos , Límite de Detección , Modelos Lineales , Oxaliplatino/sangre , Oxaliplatino/farmacocinética , Oxaliplatino/uso terapéutico , Reproducibilidad de los Resultados
14.
Biomed Chromatogr ; 34(1): e4623, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31215049

RESUMEN

Therapeutic drug monitoring (TDM) has shown to benefit patients treated with drugs of many drug classes, among which is oncology. With an increasing demand for drug monitoring, new assays have to be developed and validated. Guidelines for bioanalytical validation issued by the European Medicines Agency and US Food and Drug Administration are applicable for clinical trials and toxicokinetic studies and demand fully validated bioanalytical methods to yield reliable results. However, for TDM assays a limited validation approach is suggested based on the intended use of these methods. This review presents an overview of publications that describe method validation of assays specifically designed for TDM. In addition to evaluating current practice, we provide recommendations that could serve as a guide for future validations of TDM assays.


Asunto(s)
Antineoplásicos/análisis , Antineoplásicos/farmacocinética , Cromatografía Liquida/métodos , Monitoreo de Drogas/métodos , Espectrometría de Masas en Tándem/métodos , Antineoplásicos/uso terapéutico , Humanos , Modelos Lineales , Neoplasias/tratamiento farmacológico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
15.
Mini Rev Med Chem ; 20(1): 24-38, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31288718

RESUMEN

Tricyclic Antidepressants (TCAs) are a group of the main category of antidepressant drugs, which are commonly prescribed to treat major depressive disorder. Determination of TCA drugs is very important for clinical and forensic toxicology, especially for therapeutic drug monitoring in various biofluids. High Performance Liquid Chromatography (HPLC) is a well-established technique for this purpose. A lot of progress has been made in this field since the past 10 years. Novel extraction techniques, and novel materials for sample preparation, novel columns and novel applications of analysis of various biofluids for the determination of TCAs in combination with other drugs are some typical examples. Moreover, advances have been performed in terms of Green Analytical Chemistry principles. Herein, we aim to discuss the developed HPLC methods that were reported in the literature for the time span of 2008-2018.


Asunto(s)
Antidepresivos Tricíclicos/análisis , Antidepresivos Tricíclicos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Animales , Antidepresivos Tricíclicos/aislamiento & purificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Monitoreo de Drogas/métodos , Humanos , Extracción Líquido-Líquido/métodos , Extracción en Fase Sólida/métodos
16.
Urology ; 137: 84-90, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31877313

RESUMEN

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.


Asunto(s)
Citocromo P-450 CYP2D6/genética , Calidad de Vida , Fibrosis Retroperitoneal , Tamoxifeno , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Monitoreo de Drogas/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica/métodos , Polimorfismo de Nucleótido Simple , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fibrosis Retroperitoneal/diagnóstico por imagen , Fibrosis Retroperitoneal/tratamiento farmacológico , Fibrosis Retroperitoneal/genética , Fibrosis Retroperitoneal/psicología , Espacio Retroperitoneal/diagnóstico por imagen , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversos , Resultado del Tratamiento
17.
J Oncol Pharm Pract ; 26(1): 74-92, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30917738

RESUMEN

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.


Asunto(s)
Antineoplásicos/administración & dosificación , Asparaginasa/administración & dosificación , Instituciones Oncológicas/normas , Manejo de la Enfermedad , Monitoreo de Drogas/normas , Polietilenglicoles/administración & dosificación , Guías de Práctica Clínica como Asunto/normas , Adulto , Antineoplásicos/efectos adversos , Asparaginasa/efectos adversos , Preescolar , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Humanos , Polietilenglicoles/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Trombosis/inducido químicamente , Trombosis/epidemiología , Trombosis/prevención & control , Resultado del Tratamiento
18.
J Oncol Pharm Pract ; 26(1): 133-140, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31117914

RESUMEN

PURPOSE: The aim of this study was to test the feasibility and the usefulness of an intensive safety monitoring program to identify adverse drug reactions for medicines under additional monitoring that are used to treat cancer patients within a Portuguese oncology hospital. METHODS: This pilot intensive safety monitoring program was a three-month prospective, observational study. Patients undergoing treatment with one of the following medicines were included: nivolumab, olaparib, palbociclib, pembrolizumab, pertuzumab, ramucirumab, ribociclib, trastuzumab emtansine, or trifluridine/tipiracil. Potential eligible patients were identified by pharmacists based on prescription data. Clinicians used proper paper-based reporting forms to record adverse drug reactions. Clinical secretariats sent those reports through an electronic platform to the pharmacovigilance department for analysis. RESULTS: Seventy-five patients were on treatment with selected medicines. Of those, 33 (44%) experienced adverse drug reactions: 23 (69.7%) cases were serious and 5 (15.2%) unexpected. Considering the number of patients exposed to each medicine and the number of patients experiencing adverse drug reactions, trifluridine/tipiracil (72.7%; 8/11) was associated with the highest rate of toxicity, followed by olaparib (66.7%; 2/3), trastuzumab emtansine (50.0%; 3/6), pertuzumab (47.8%; 11/23), pembrolizumab (45.5%; 5/11), palbociclib (25.0%; 1/4), and nivolumab (18.8%; 3/16). A total of 59 adverse drug reactions were identified (i.e. 1.8 adverse drug reactions/patient), mainly gastrointestinal disorders (n = 15; 25.4%), and blood and lymphatic system disorders (n = 14; 23.7%). CONCLUSION: This intensive safety monitoring program was feasible and allowed identifying serious and unexpected adverse drug reactions, adding value to pharmacovigilance and therefore contributing to improve patient safety. Further research is needed to confirm the findings of this pilot study.


Asunto(s)
Antineoplásicos/efectos adversos , Instituciones Oncológicas/normas , Monitoreo de Drogas/normas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Seguridad del Paciente/normas , Farmacovigilancia , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos/normas , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Monitoreo de Drogas/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Proyectos Piloto , Portugal/epidemiología , Estudios Prospectivos
19.
J Pharm Biomed Anal ; 177: 112853, 2020 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-31499431

RESUMEN

Tacrolimus (TAC) is an immunosuppressant for preventing solid-organ transplant rejection. Because of its narrow therapeutic window, analytical methods which can detect TAC in serum samples with high accuracy and reliability are required. In this study, specific aptamers (Apt122 and Apt125) for TAC were isolated via systematic evolution of ligands by exponential enrichment method using magnetic beads to immobilize the target. After determination of binding constants of aptamers by flow cytometry analysis, Apt122 was selected and labeled with ATTO 647 N as a fluorophore to develop a fluorescent sensing platform for detection of TAC using graphene oxide (GO) as a fluorescence quencher. The designed aptasensor could detect TAC in phosphate buffer saline (10 mM PBS) and serum samples with detection limits as low as 1.4 and 2.5 nM, respectively.


Asunto(s)
Aptámeros de Nucleótidos/química , Monitoreo de Drogas/métodos , Inmunosupresores/sangre , Técnica SELEX de Producción de Aptámeros/métodos , Tacrolimus/sangre , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Monitoreo de Drogas/instrumentación , Estudios de Factibilidad , Colorantes Fluorescentes/química , Grafito/química , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/química , Ligandos , Límite de Detección , Reproducibilidad de los Resultados , Tacrolimus/administración & dosificación , Tacrolimus/química
20.
J Pharm Biomed Anal ; 177: 112858, 2020 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-31518862

RESUMEN

Eliglustat is an oral substrate reduction therapy drug and has been approved as a first-line treatment for adults with Gaucher disease type 1 (GD 1). In the present study, we aimed to develop and establish an accurate and simple ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the measurement of eliglustat concentration in rat plasma. The goal of chromatographic separation of eliglustat and the internal standard (bosutinib) was finished on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 µm) column. Acetonitrile and 0.1% formic acid in water were employed as the mobile phase in a mode of gradient elution with the 0.40 mL/min flow rate. The detection was carried out on a XEVO TQ-S triple quadrupole tandem mass spectrometer coupled with electrospray ionization (ESI) interface in the positive-ion mode. Multiple reaction monitoring (MRM) was used to monitor the precursor-to-product ion transitions of m/z 405.4 → 84.1 for eliglustat and m/z 530.2 → 141.2 for bosutinib (IS), respectively. It was found that the linearity of the method in the range of 1-500 ng/mL was good for eliglustat. The values of intra- and inter-day accuracy and precision were all within the acceptance limits, and no matrix effect was found in this method. The current developed method was further performed to support in vivo pharmacokinetic study of eliglustat after oral treatment with 10 mg/kg eliglustat to rats.


Asunto(s)
Monitoreo de Drogas/métodos , Inhibidores Enzimáticos/farmacocinética , Enfermedad de Gaucher/tratamiento farmacológico , Pirrolidinas/farmacocinética , Administración Oral , Compuestos de Anilina/administración & dosificación , Compuestos de Anilina/sangre , Animales , Cromatografía Líquida de Alta Presión/métodos , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/sangre , Estudios de Factibilidad , Humanos , Límite de Detección , Masculino , Nitrilos/administración & dosificación , Nitrilos/sangre , Pirrolidinas/administración & dosificación , Pirrolidinas/sangre , Quinolinas/administración & dosificación , Quinolinas/sangre , Ratas , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos
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