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1.
Proc Natl Acad Sci U S A ; 117(7): 3509-3517, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019879

RESUMO

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used "red blood cell mimicry" to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.


Assuntos
Monitoramento de Medicamentos/métodos , Eritrócitos/química , Sódio/sangue , Animais , Circulação Sanguínea , Monitoramento de Medicamentos/instrumentação , Fluorescência , Camundongos , Camundongos Nus , Mimetismo Molecular , Ratos
2.
Talanta ; 209: 120560, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892051

RESUMO

Antipsychotic clozapine is the most effective medication currently available for schizophrenia. However, clozapine is dramatically underutilized due to its harsh side effects that are not effectively monitored. By continuously monitoring clozapine blood levels, such as use of an implantable glucometer, which has transformed diabetes management, the treatment can be optimized and side effects will be minimized. Currently, none of the methods for clozapine detection show the ability to repeatedly measure clozapine in whole blood without pretreatment steps. Here we propose using a microelectrode modified with reduced graphene oxide-a material that was used for repeatable measurements in implantable electrochemical devices. We present the successful direct electrodeposition of reduced-graphene oxide coating onto microelectrodes. Systematic characterization of the electrodeposition technique parameters (i.e., the technique scan rate and the number of cycles) revealed their effect on the electrochemical activity and the structural properties (the film thickness and roughness) of the films. The developed reduced-graphene oxide-modified microelectrode exhibited the feasibility to detect clozapine in microliters-volume-samples of whole blood with a limit-of-detection and a sensitivity of 0.64 ±â€¯0.04 µM and 19.6 ±â€¯1.3 µA/cm2µM, respectively. Moreover, the reduced graphene oxide-modified microelectrodes exhibited high repeatability (retaining 94.6% of the electrochemical signal after 10 repeats), reproducibility (3.6% relative standard deviation), and storage stability (retaining 89% of the electrochemical signal after 4 weeks). Finally, relative recovery studies of 0.5, 1, and 2 µM clozapine concentrations resulted in 108 ±â€¯4.0%, 112 ±â€¯3.5%, and 103 ±â€¯2.2%, respectively. Future studies should investigate the microelectrode fouling mechanisms in whole blood and explore methods to overcome fouling.


Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Técnicas Eletroquímicas/instrumentação , Grafite/química , Monitoramento de Medicamentos/instrumentação , Desenho de Equipamento , Humanos , Limite de Detecção , Microeletrodos , Oxirredução
3.
J Pharm Biomed Anal ; 177: 112853, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31499431

RESUMO

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.


Assuntos
Aptâmeros de Nucleotídeos/química , Monitoramento de Medicamentos/métodos , Imunossupressores/sangue , Técnica de Seleção de Aptâmeros/métodos , Tacrolimo/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Monitoramento de Medicamentos/instrumentação , Estudos de Viabilidade , Corantes Fluorescentes/química , Grafite/química , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/química , Ligantes , Limite de Detecção , Reprodutibilidade dos Testes , Tacrolimo/administração & dosagem , Tacrolimo/química
4.
J Pharm Biomed Anal ; 177: 112842, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31526960

RESUMO

BACKGROUND: Anti-drug-antibodies (ADA) against infliximab are frequently measured in patients receiving infliximab treatment with loss of response and undetectable infliximab concentrations. Different ADA bridging assays (1st generation, 2nd generation and ready-to-use kit) have been developed successively and were applied over the last 10 years, making comparison between ADA concentrations very challenging. A cutoff of 8 µg/ml was established to discriminate low from high ADA concentrations using the 1st generation ADA bridging assay. The objective of this study was to enable comparison of ADA concentrations determined with the different assays that were developed over the years. METHODS: 166 serum samples were collected from patients with inflammatory bowel disease treated with infliximab. 98 samples were measured simultaneously with the 1st and 2nd generation ADA assay, 67 serum samples were measured with the 2nd generation assay and the ready-to-use kit. RESULTS: From our ADA concentration comparison experiments, we deduced that the previously established cutoff of 8 µg/ml with the 1st generation ELISA has a similar impact as the cutoff of 374 ng/ml with the 2nd generation ELISA and a cutoff of 119 ng/ml in the ready-to-use ELISA kit. CONCLUSION: ADA concentrations measured with the different assays were compared and a cutoff concentration was determined for each of them to distinguish between low and high ADA concentrations. These cutoff concentrations may serve as a tool for clinicians to make treatment decisions for patients with a loss of response to infliximab and undetectable infliximab serum concentrations.


Assuntos
Anticorpos/sangue , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/imunologia , Anticorpos/imunologia , Calibragem , Tomada de Decisão Clínica/métodos , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Resistência a Medicamentos , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Estudos de Viabilidade , Fármacos Gastrointestinais/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Infliximab/administração & dosagem , Sensibilidade e Especificidade
5.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 12: 468-475, jan.-dez. 2020. ilus, tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1087433

RESUMO

Objetivo: a avaliação da cultura de segurança do paciente permite aos hospitais identificar e gerir prospectivamente questões relevantes de segurança em suas rotinas de trabalho. Método: estudo quantitativo, transversal e descritivo, ocorrida no ano de 2017 na Unidade de Terapia Intensiva Adulta em um hospital privado, localizado em Niterói/RJ. A população foram os profissionais médicos e equipe de enfermagem, utilizando análise estatística por meio de programa R, com a interface Rcmdr. Resultados: baseados nas respostas às perguntas sobre notificação de eventos aplicada com a Pesquisa de Cultura de Segurança do Paciente a 97 profissionais, com uma taxa de resposta de 85,6%, correspondendo a 83 profissionais. Menos de 45% dos participantes da pesquisa sempre notificam um erro, engano ou falha, que afete ou não o paciente, 59,0% não fizeram nenhuma notificação nos últimos 12 meses antecedentes à pesquisa e não houve diferença significativa na quantidade de notificação que destacasse uma categoria profissional, graduados ou não. Discussão: houve maior adesão à notificação de eventos pelos com maior tempo de hospital e com maior tempo naquela terapia intensiva. Não se encontrou correlação do número de notificações relatadas com o tempo de profissão e com a carga horária de trabalho. Conclusão: no que tange à conscientização de incrementar a adesão à notificação de eventos, a análise realizada contribuiu para a melhoria da segurança do paciente


Objective: ealuating the patient's safety culture allows hospitals to identify and manage relevant safety issues prospectively in their work routines. Method: a quantitative, transversal and descriptive study, carried out in 2017 at the Adult Intensive Care Unit in a private hospital, located in Niterói / RJ. The population were medical professionals and nursing staff, using statistical analysis through program R, with the Rcmdr interface. Results: based on responses to questions about event notification applied with the Patient Safety Culture Survey to 97 professionals, with a response rate of 85.6%, corresponding to 83 professionals. Less than 45% of respondents report an error, deception, or failure, affecting the patient, 59.0% did not report in the last 12 months prior to the survey, and there was no significant difference in the amount of notification that stood out a professional category, graduates or not. Discussion: there was greater adherence to the notification of events by those with longer hospital time and with more time in that intensive therapy. There was no correlation between the number of reports reported with the time of profession and the workload. Conclusion: with regard to the awareness of increasing adherence to event notification, the analysis performed contributed to the improvement of patient safety


Objetivo: la evaluación de la cultura de seguridad del paciente permite a los hospitales identificar y gestionar prospectivamente cuestiones relevantes de seguridad en sus rutinas de trabajo. Método: estudio cuantitativo, transversal y descriptivo, ocurrido en el año 2017 en la Unidad de Terapia Intensiva Adulta en un hospital privado, ubicado en Niterói / RJ. La población fueron los profesionales médicos y equipo de enfermería, utilizando análisis estadístico por medio del programa R, con la interfaz Rcmdr. Resultados: basados en las respuestas a las preguntas sobre notificación de eventos aplicada con la Encuesta de Cultura de Seguridad del Paciente a 97 profesionales, con una tasa de respuesta del 85,6%, correspondiendo a 83 profesionales. En la mayoría de los casos, la mayoría de las personas que sufren de la enfermedad de Alzheimer, una categoría profesional, graduados o no. Discusión: hubo mayor adhesión a la notificación de eventos por los con mayor tiempo de hospital y con mayor tiempo en aquella terapia intensiva. No se encontró correlación del número de notificaciones relatadas con el tiempo de profesión y con la carga horaria de trabajo. Conclusión: en lo que concierne a la concientización de incrementar la adhesión a la notificación de eventos, el análisis realizado contribuyó a la mejora de la seguridad del paciente


Assuntos
Humanos , Monitoramento de Medicamentos/instrumentação , Segurança do Paciente/estatística & dados numéricos , Estudos Transversais , Fatores de Risco , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Medição de Risco , Unidades de Terapia Intensiva
6.
Anal Chim Acta ; 1096: 76-88, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883594

RESUMO

In this work, we developed cerium oxide/tin oxide (CeO2/SnO2) nanocatalyst with the assistance of urea by a simple sonochemical method and utilized as an efficient electrode material for electrochemical sensing of anti-inflammatory drug 5-aminosalicylic acid (Mesalamine, MES). The CeO2/SnO2 nanoparticles (NPs) were systematically characterized in terms of their crystal structure, morphologies, and physicochemical properties using XRD, Raman, FESEM, HR-TEM, EDX, mapping, and XPS analysis. The characterization results clearly confirmed that the prepared NPs was formed in the phase of CeO2/SnO2 without any other impurities. The electrochemical properties of CeO2/SnO2 NPs were investigated by EIS, CV, and DPV techniques. The CeO2/SnO2 NPs (9.6 µA) modified GCE demonstrated an excellent and improved electrocatalytic activity in terms of higher anodic peak current and lower peak potential when compared to bare GCE (6.7 µA) and CeO2 NPs/GCE (8.2 µA) for the sensing of MES. The CeO2/SnO2 NPs/GCE shows broader linear response range and lower detection limit of 0.02-1572 µM and 0.006 µM, respectively. Moreover, other potentially interfering compounds such as a similar functional group containing biological substances and inorganic species have no interference effect towards MES sensing. In addition, the practicability of the CeO2/SnO2 NPs/GCE was tested by real sample analysis in commercial MES tablet, human urine, and serum samples with the appreciable recovery results.


Assuntos
Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/urina , Cério/química , Mesalamina/sangue , Mesalamina/urina , Compostos de Estanho/química , Catálise , Monitoramento de Medicamentos/instrumentação , Técnicas Eletroquímicas/instrumentação , Eletrodos , Humanos , Limite de Detecção , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Sonicação
7.
Intern Med J ; 49(11): 1442-1446, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31713344

RESUMO

Vitamin K antagonists are widely used, yet have a slim therapeutic margin and high iatrogenicity. Patients are monitored through international normalised ratio (INR) by venipuncture, but coagulometers could measure INR by capillary puncture. This prospective study evaluated the clinical concordance of capillary INR versus venous INR in 31 nursing home patients. Concordance was good and mean time in therapeutic range (TTR) markedly increased. Capillary INR is thus reliable, could improve TTR and decrease iatrogenicity.


Assuntos
Coeficiente Internacional Normatizado/instrumentação , Flebotomia/métodos , Sistemas Automatizados de Assistência Junto ao Leito/normas , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Capilares , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Feminino , Fibrinolíticos/uso terapêutico , Idoso Fragilizado , França , Instituição de Longa Permanência para Idosos , Humanos , Coeficiente Internacional Normatizado/normas , Masculino , Casas de Saúde , Estudos Prospectivos , Veias , Vitamina K/antagonistas & inibidores
8.
PLoS One ; 14(11): e0224751, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738773

RESUMO

BACKGROUND: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting. METHODS: Serum samples were obtained from 270 patients who received direct acting antiviral therapy with different treatment regimens at two study sites (Hannover and Frankfurt) in 2016. Overall, 1545 samples (baseline, on-treatment and follow-up) were tested in parallel by both assays. RESULTS: The mean difference between cobas HCV and CAP/CTM for the quantification of HCV RNA was 0.008 log10 IU/ml HCV RNA (95% limits of agreement: -0.02-0.036) showing excellent agreement of both assays. With respect to clinical cut offs (HCV RNA detectable vs. target not detected and HCV RNA above the lower limit of quantification (LLOQ) vs.

Assuntos
Antivirais/administração & dosagem , Monitoramento de Medicamentos/instrumentação , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Carga Viral/efeitos dos fármacos , Adulto , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Técnicas de Diagnóstico Molecular/instrumentação , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/instrumentação
10.
Artigo em Inglês | MEDLINE | ID: mdl-31627440

RESUMO

Smart pillboxes that remind patients to take medication may help avoid unintended non-adherence to medication regimens. To better understand the implementation potential of smart pillboxes among patients with chronic diseases, this study aimed to explore patients' acceptability to use such devices and its associated factors. Five-hundred primary care patients aged 40 years or older were randomly recruited from a government-funded primary care clinic in Hong Kong. Patients were asked (i) if they needed to take medication daily, (ii) how many daily oral medications they needed to take on average, (iii) if they had ever missed a dose by accident, and (iv) if they were willing to use a smart pillbox for free to remind them to take medication. Out of the 344 participants included in the analysis who needed to take daily oral medication, 49.1% reported having previously missed a dose by accident, and 70.6% were willing to use a smart pillbox for free. A multiple logistic regression model found that male patients (adjusted odds ratio (aOR): 0.59) and patients with hypertension (aOR: 0.56) were less likely to have previously missed a dose by accident. Patients who needed to take a greater number of daily medications (aOR: 1.16), who had previously missed a dose by accident (aOR: 2.44), with heart disease (aOR: 3.67) and with a high monthly income (aOR: 2.30) were more willing to use a smart pillbox, while older patients (aOR: 0.95) were less willing to do so. Primary care patients who reported missing a dose by accident were 2.4 times as likely to want to use a smart pillbox while those with heart disease were almost 4 times as likely to want to use a smart pillbox. Further studies such as those evaluating the willingness to pay for smart pillboxes and randomised control trials to evaluate the effectiveness of smart pillboxes in enhancing medication adherence should be conducted to provide more evidence about the implementation potential of such devices.


Assuntos
Monitoramento de Medicamentos/instrumentação , Adesão à Medicação , Atenção Primária à Saúde , Adulto , Idoso , Doença Crônica , Feminino , Hong Kong , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Projetos Piloto
11.
Nutrients ; 11(9)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491873

RESUMO

Elevated blood concentration of low-density lipoprotein cholesterol (LDLc) is a primary risk factor for developing cardiovascular disease. Lifestyle interventions including an increase in dietary phytosterols as well as medications have proven effective in lowering LDLc. The primary objective of this randomized, placebo controlled, double blind, crossover study was to determine the impact of a new phytosterol emulsion for dietary supplements (1.5 g/day phytosterol equivalents) on LDLc concentrations. Thirty-two healthy adults were randomly assigned to receive placebo or treatment followed by a washout period, followed by placebo or treatment, each phase lasting one month. Secondary endpoints related to cardiovascular health were also assessed. Study management, including screening, recruitment, monitoring, compliance, and data collection, were done remotely (a siteless clinical trial) utilizing a novel virtual tool. Phytosterol supplementation significantly lowered LDLc concentrations by 10.2% (16.17 mg/dL or 0.419 mmol/L, p = 0.008 by paired t-test, p = 0.014 by Wilcoxon signed rank testing). No secondary biomarkers were found to change significantly. Supplementation with phytosterols in a new dietary supplement formulation efficiently and safely decreases LDLc within one month in a free-living setting.


Assuntos
Anticolesterolemiantes/administração & dosagem , LDL-Colesterol/sangue , Suplementos Nutricionais , Monitoramento de Medicamentos/instrumentação , Fitosteróis/administração & dosagem , Adulto , Idoso , Anticolesterolemiantes/química , Biomarcadores/sangue , Células CACO-2 , Estudos Cross-Over , Método Duplo-Cego , Regulação para Baixo , Composição de Medicamentos , Emulsões , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Fitosteróis/química , Fatores de Tempo
12.
J Pharm Biomed Anal ; 176: 112799, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31394306

RESUMO

Electrochemistry (EC) coupled with liquid chromatography and tandem mass spectrometry (HPLC/ESI-MS/MS) was used to study the oxidation products of cyclosporine A (CYC), everolimus (EWE), mycophenolic acid (MFA), sirolimus (SIR) and tacrolimus (TAK). Mimicry of the oxidative phase I and II metabolism was achieved in a thin-layer cell equipped with a boron doped diamond (BDD) working electrode. Structures of the electrochemically generated products were elucidated on the basis of MS/MS experiments. Additionally, a sensitive, specific and rapid HPLC-MS/MS method has been developed and validated for the quantification of selected drugs and their metabolites in human serum. Sample preparation was accomplished through microextraction by packed sorbent (MEPS) process. Finally, the identification of electrochemical products was done and results were compared with known metabolites of studied immunosuppressant drugs. Electrochemical conversion of target compounds has appeared as a new pseudo-in vitro instrumental technology for the prediction of potential metabolites, since the oxidation products have also been identified in serum samples.


Assuntos
Monitoramento de Medicamentos/métodos , Técnicas Eletroquímicas/métodos , Rejeição de Enxerto/sangue , Imunossupressores/sangue , Idoso , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/instrumentação , Técnicas Eletroquímicas/instrumentação , Eletrodos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/isolamento & purificação , Imunossupressores/metabolismo , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Oxirredução , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodos
13.
Nano Lett ; 19(9): 6346-6351, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31381353

RESUMO

Levodopa is the standard medication clinically prescribed to patients afflicted with Parkinson's disease. In particular, the monitoring and optimization of levodopa dosage are critical to mitigate the onset of undesired fluctuations in the patients' physical and emotional conditions such as speech function, motor behavior, and mood stability. The traditional approach to optimize levodopa dosage involves evaluating the subjects' motor function, which has many shortcomings due to its subjective and limited quantifiable nature. Here, we present a wearable sweat band on a nanodendritic platform that quantitatively monitors levodopa dynamics in the body. Both stationary iontophoretic induction and physical exercise are utilized as our methods of sweat extraction. The sweat band measures real-time pharmacokinetic profiles of levodopa to track the dynamic response of the drug metabolism. We demonstrated the sweat band's functionalities on multiple subjects with implications toward the systematic administering of levodopa and routine management of Parkinson's disease.


Assuntos
Monitoramento de Medicamentos/instrumentação , Levodopa , Doença de Parkinson , Suor/metabolismo , Dispositivos Eletrônicos Vestíveis , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/farmacocinética , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
14.
Clin Appl Thromb Hemost ; 25: 1076029619867137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364394

RESUMO

To describe the effect of dabigatran on thrombin time (TT) reagents at different concentrations of thrombin. Pooled normal plasma enriched with dabigatran was dissolved in dimethylsulfoxide (DMSO) at concentrations of 0, 20, 50, 100, 200, 300, and 500 ng/mL. Samples with each concentration were evaluated using a semiautomatic coagulation analyzer to assess the effect of dabigatran on internal normalized ratio (INR), thromboplastin time (APTT), and TT, which were purchased from Instrument Laboratory (IL), Sysmex (SYS), and Stago (STA), respectively. Regarding INR, no reagent showed good sensitivity to increasing concentration of dabigatran, despite all reagents showing good linear response curves (P = .012). Regarding APTT, all reagents had low sensitivity to increasing dabigatran concentration, but SYS-APTT showed a better linear response curve (P = .001). Regarding TT, all reagents had a good linear response to the concentration of dabigatran; however, SYS-TT was very sensitive at low concentrations of dabigatran (0-100 ng/mL), while IL (TT-5 mL) and STA-TT were sensitive at medium concentrations of dabigatran (0-300 ng/mL), and IL (TT-2 mL) was less sensitive for a wide concentration of dabigatran (0-500 ng/mL; P = .007). Internal normalized ratio and APTT showed low sensitivity and SYS-TT showed high sensitivity to concentrations of dabigatran that were unsuitable to monitor. Both IL (TT-5 mL) and STA-TT were useful at medium concentrations of dabigatran by semiautomatic coagulation analyzer, which calculated results using the end point method of coagulation. Instrument Laboratory (TT-2 mL), which contains a higher concentration of thrombin, had better sensitivity to the concentration of dabigatran than APTT and was suitable for routine monitoring by an automatic analyzer.


Assuntos
Dabigatrana/farmacocinética , Monitoramento de Medicamentos/métodos , Tempo de Trombina , Antitrombinas/sangue , Antitrombinas/farmacocinética , Testes de Coagulação Sanguínea , Dabigatrana/sangue , Dabigatrana/normas , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Humanos , Indicadores e Reagentes/farmacologia , Tempo de Tromboplastina Parcial , Sensibilidade e Especificidade , Trombina/farmacologia
15.
Pharmacol Res Perspect ; 7(4): e00483, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31333845

RESUMO

A central venous catheter with a built-in microdialysis membrane is available for continuous lactate and glucose monitoring in the intensive care unit (ICU). As this catheter might also be suitable for repeated measurements of unbound drug levels, we studied in vitro the feasibility of monitoring unbound antibiotic concentrations. The catheter was placed in various media at 37°C spiked with gentamicin or vancomycin. Dialysate fractions were repeatedly collected over 3 hours with a NaCl 0.9% perfusate flow of 5 µL/min. Total and unbound drug concentrations in medium and perfusate were measured by immunoassay. After 60 minutes stable recovery for both drugs was observed, with mean ±SD relative recoveries of vancomycin and gentamicin in human serum of 64% ±0.4% and 73% ±3%. The recoveries of the unbound concentrations were 91% ±3% and 91% ±4%. This intravenous microdialysis system may be a very useful platform for therapeutic drug monitoring in the ICU.


Assuntos
Monitoramento de Medicamentos/instrumentação , Gentamicinas/farmacocinética , Soro/química , Vancomicina/farmacocinética , Administração Intravenosa , Cateteres , Estudos de Viabilidade , Humanos , Técnicas In Vitro , Microdiálise/instrumentação
16.
J Chromatogr A ; 1601: 95-103, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31208795

RESUMO

Fully automated dried blood spot (DBS) extraction systems, online coupled to standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) configurations, decrease the hands-on time associated with conventional DBS analysis, resulting in a higher sample throughput, making the technique more compatible with a high-capacity bioanalytical workflow. The aim of this study was to develop and validate an LC-MS/MS method, using a DBS-MS 500 autosampler, for the determination and quantification of four anti-epileptic drugs (carbamazepine, valproic acid, phenobarbital and phenytoin) and one active metabolite (carbamazepine-10,11-epoxide) in DBS samples. Method development included thorough optimization of the fully automated extraction procedure (i.e. extraction solvent, extraction (loop) volume, internal standard application, internal standard drying time, etc.). The method was fully validated based on international guidelines. Accuracy (%bias), as well as precision (%RSD) (with a single exception) were below 13%. Neither carry-over nor unacceptable interferences were observed. All compounds were stable in DBS for at least 1 month when stored at room temperature, 4 °C and -20 °C and for at least 4 days when stored at 60 °C. Internal standard-corrected matrix effects were below 8%, with %RSDs below 9.1%. Reproducible relative recovery values (around 60% for all analytes) were obtained and the effect of the hematocrit on the relative recovery was overall limited. Successful application on capillary patient samples originating from developing countries demonstrated the applicability of the developed procedure in a remote setting.


Assuntos
Anticonvulsivantes/análise , Teste em Amostras de Sangue Seco , Monitoramento de Medicamentos/métodos , Anticonvulsivantes/sangue , Automação , Cromatografia Líquida , Teste em Amostras de Sangue Seco/normas , Monitoramento de Medicamentos/instrumentação , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
17.
Drug Test Anal ; 11(9): 1444-1452, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150570

RESUMO

Dihydroartemisinin (DHA) and piperaquine (PPQ) are two drugs used in an artemisinin-based combination therapy (ACT). The circulation of counterfeit antimalarial drugs demands the development of simple, point-of-care (POC) tests for monitoring drug quality. Here we aimed to design an antibody-based lateral flow dipstick assay for simultaneous quality control of DHA and PPQ. To obtain a monoclonal antibody (mAb) for PPQ, one structural unit of the symmetric PPQ molecule was used to derive a carboxylic acid for linkage to a carrier protein as immunogen. Screening of hybridoma cells identified an mAb 4D112B2 that reacted with the PPQ-based immunogen. A highly-sensitive icELISA was designed based on this mAb, which showed 50% inhibition concentration of PPQ at 1.66 ng/mL and a working range of 0.35 - 7.40 ng/mL. The mAb showed 10.2, 15.9 and 30.4% cross reactivity to hydroxychloroquine sulfate, chloroquine and amodiaquine, respectively. No cross reactivity was observed to lumefantrine, mefloquine artemisinin and its derivatives. Using our previous DHA dipstick design, a lateral flow dipstick for simultaneous analysis of PPQ and DHA was developed. The indicator ranges for PPQ and DHA were 2 - 5 µg/mL and 250 - 500 ng/mL, respectively. The dipstick was used to semi-quantitatively analyze PPQ and DHA content in commercial ACT drugs, which produced agreeable results to those determined by high-performance liquid chromatography. This combination dipstick makes it a potential POC device for quality control of the two active ingredients in a commonly used ACT.


Assuntos
Antimaláricos/análise , Artemisininas/análise , Ensaio de Imunoadsorção Enzimática/métodos , Quinolinas/análise , Animais , Anticorpos Monoclonais/química , Combinação de Medicamentos , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/instrumentação , Desenho de Equipamento , Camundongos , Sistemas Automatizados de Assistência Junto ao Leito , Fitas Reagentes/análise
18.
Anal Chim Acta ; 1070: 69-79, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31103169

RESUMO

Nonadherence to antihypertensive drugs therapy is known to be a serious issue in hypertension treatment. Liquid chromatography (LC) coupled to mass spectrometry (MS) was shown to allow the assessment of such nonadherence in blood and urine sample. However, their sampling may represent a logistical challenge and are often not favored by the patients. We questioned whether oral fluid (OF) might be an easier accessible alternative matrix for adherence monitoring of cardiovascular drugs (CD). A qualitative method for adherence monitoring of 78 commonly prescribed cardiovascular drugs in OF using LC high-resolution MS (LC-HRMS/MS) was therefore developed, validated, and used to study the presence of antihypertensive medication in OF. Selectivity, ion suppression and enhancement due coeluting analytes, carry over, limits of detection (LOD), limits of identification (LOI), recovery (RE), matrix effects (ME), and process efficiency (PE) were investigated. For demonstrating applicability, over 50 OF samples were investigated and data were compared to findings in blood and urine. Selectivity in OF was given for all compounds via their MS2 spectra and no total suppression of signals could be observed. Determined LOI in OF for ten analytes was higher than the given therapeutic plasma concentration. Furthermore, RE, ME, and PE were in acceptable ranges for more than 65% of the compounds. In total, 208 prescriptions of CD to 57 patients were analyzed and demonstrated the suitability of for adherence monitoring in principle. OF was comparable to plasma regarding the drug categories and the frequencies of hits, except for acidic compounds but more hits could be found in urine samples. A analytical method using OF as analytical matrix was successfully developed. Application showed that it might be a suitable alternative for adherence monitoring of selected drugs in the future, particularly those having no acidic function.


Assuntos
Anti-Hipertensivos/análise , Líquidos Corporais/química , Monitoramento de Medicamentos/métodos , Adesão à Medicação , Cromatografia Líquida/instrumentação , Monitoramento de Medicamentos/instrumentação , Humanos , Espectrometria de Massas em Tandem/instrumentação
19.
ACS Sens ; 4(4): 1072-1080, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30950598

RESUMO

Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual. New sensing approaches that track antimicrobial concentration for each patient in real time could allow individualized drug dosing. This work presents a potentiometric microneedle-based biosensor to detect levels of ß-lactam antibiotics in vivo in a healthy human volunteer. The biosensor is coated with a pH-sensitive iridium oxide layer, which detects changes in local pH as a result of ß-lactam hydrolysis by ß-lactamase immobilized on the electrode surface. Development and optimization of the biosensor coatings are presented, giving a limit of detection of 6.8 µM in 10 mM PBS solution. Biosensors were found to be stable for up to 2 weeks at -20 °C and to withstand sterilization. Sensitivity was retained after application for 6 h in vivo. Proof-of-concept results are presented showing that penicillin concentrations measured using the microneedle-based biosensor track those measured using both discrete blood and microdialysis sampling in vivo. These preliminary results show the potential of this microneedle-based biosensor to provide a minimally invasive means to measure real-time ß-lactam concentrations in vivo, representing an important first step toward a closed-loop therapeutic drug monitoring system.


Assuntos
Antibacterianos/análise , Técnicas Biossensoriais/métodos , Monitoramento de Medicamentos/métodos , Agulhas , Penicilina G/análise , Penicilina V/análise , Antibacterianos/química , Técnicas Biossensoriais/instrumentação , Monitoramento de Medicamentos/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Hidrólise , Irídio/química , Limite de Detecção , Penicilina G/química , Penicilina V/química , Estudo de Prova de Conceito , beta-Lactamases/química
20.
Curr Pharm Biotechnol ; 20(5): 390-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961482

RESUMO

BACKGROUND: The efficient analytical method for the analysis of nonsteroidal antiinflammatory drugs (NSAIDs) in a biological fluid is important for determining the toxicological aspects of such long-term used therapies. METHODS: In the present work, multi-walled carbon nanotubes reinforced into a hollow fiber by chitosan sol-gel assisted-solid/ liquid phase microextraction (MWCNTs-HF-CA-SPME) method followed by the high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed for the determination of three NSAIDs, ketoprofen, diclofenac, and ibuprofen in human urine samples. MWCNTs with various dimensions were characterized by various analytical techniques. The extraction device was prepared by immobilizing the MWCNTs in the pores of 2.5 cm microtube via chitosan sol-gel assisted technology while the lumen of the microtube was filled with few microliters of 1-octanol with two ends sealed. The extraction device was operated by direct immersion in the sample solution. RESULTS: The main factors influencing the extraction efficiency of the selected NSAIDs have been examined. The method showed good linearity R2 ≥ 0.997 with RSDs from 1.1 to 12.3%. The limits of detection (LODs) were 2.633, 2.035 and 2.386 µg L-1, for ketoprofen, diclofenac, and ibuprofen, respectively. The developed method demonstrated a satisfactory result for the determination of selected drugs in patient urine samples and comparable results against reference methods. CONCLUSION: The method is simple, sensitive and can be considered as an alternative for clinical laboratory analysis of selected drugs.


Assuntos
Anti-Inflamatórios não Esteroides/urina , Quitosana/química , Monitoramento de Medicamentos/métodos , Nanotubos de Carbono/química , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/instrumentação , Humanos , Limite de Detecção , Microextração em Fase Líquida , Microextração em Fase Sólida
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