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Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial. CYP3A5, ABCB1 and two POR genotypes were assessed by real-time PCR. The impact on TAC pharmacokinetics of individual genetic variants on CYP3A5 nonexpressors was evaluated by genetic score. Explicative models for TAC AUC0-24h, Cmax and Cmin after Advagraf were developed by linear regression. The built genetic scores explain 13.7 and 26.5% of the total AUC0-24h and Cmin total variability, respectively. Patients genetic information should be considered to monitorizate and predict TAC exposure.
Assuntos
Citocromo P-450 CYP3A/genética , Sistema Enzimático do Citocromo P-450/genética , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Criança , Feminino , Variação Genética/genética , Genótipo , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/genética , Humanos , Transplante de Rim/métodos , MasculinoRESUMO
INTRODUCTION: Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route. OBJECTIVES: Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity. METHODS: This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis. RESULTS: After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods. CONCLUSION: To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.
Assuntos
Metabolômica/métodos , Zonisamida/metabolismo , Zonisamida/farmacocinética , Adulto , Anticonvulsivantes/sangue , Anticonvulsivantes/metabolismo , Área Sob a Curva , Feminino , Voluntários Saudáveis , Humanos , Isoxazóis/sangue , Masculino , Fenômenos Farmacológicos/fisiologia , Equivalência Terapêutica , Adulto JovemRESUMO
The original version of this article contains a mistake.
RESUMO
INTRODUCTION: The aim of this study is to establish the risk of thromboembolic events and evaluation of the use of venous thromboembolism prophylaxis in hospitalized medical patients and after discharge, and their concordance with protocols used in our hospital. MATERIAL AND METHODS: We performed a cross-sectional with prospective follow-up until hospital discharge. It included all medical patients in Internal Medicine, Pneumology and Oncology Departments. The patient's thromboembolic risk and type of thromboembolism prophylaxis indication during hospitalization and after discharge were determined. RESULTS: A total of 116 patients (52 in Internal Medicine Department, 35 in Pneumology Department and 29 in Oncology Department), with a mean age of 67 +/- 17 years (35 females; 81 males) were included. During hospitalization, 62.9% of the patients had a high risk of thromboembolic events, 3.4% a moderate risk, 23.3% low risk, and 10.3% had no risk. After discharge, these proportions were 35.6%, 3.8%, 24% and 34.6%, respectively. A total of 49.1% of the patients had an adequate indication of venous thromboembolism prophylaxis during the hospitalization and after discharge.
Assuntos
Anticoagulantes/uso terapêutico , Hospitalização , Alta do Paciente , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Idoso , Estudos Transversais , Uso de Medicamentos , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
Introducción. El objetivo de este estudio es conocer el riesgo de enfermedad tromboembólica venosa (ETV) en pacientes médicos durante su ingreso y al alta hospitalaria, y estudiar los hábitos de prescripción de tromboprofilaxis y su adecuación a los protocolos utilizados en nuestro medio. Material y método. Para ello se realizó un estudio transversal con seguimiento prospectivo hasta el alta hospitalaria. Se incluyeron pacientes médicos de los Servicios de Medicina Interna, Neumología y Oncología, en los que se determinó el grado de riesgo de ETV y el tipo de indicación de tromboprofilaxis durante el ingreso y al alta hospitalaria. Resultados. Se incluyeron 116 pacientes (52 en medicina interna, 35 en neumología y 29 en oncología), con una media de edad de 67 ± 17 años (35 mujeres; 81 hombres). En el ingreso el 62,9% tenían alto riesgo de ETV, el 3,4% moderado, el 23,3% bajo y el 10,3% no tenían riesgo. Al alta hospitalaria estos porcentajes fueron de 35,6; 3,8; 24 y 34,6%, respectivamente. La proporción de pacientes con prescripción adecuada a la indicación fue del 49,1%, tanto durante el ingreso como al alta hospitalaria (AU)
Introduction. The aim of this study is to establish the risk of thromboembolic events and evaluation of the use of venous thromboembolism prophylaxis in hospitalized medical patients and after discharge, and their concordance with protocols used in our hospital. Material and methods. We performed a cross-sectional with prospective follow-up until hospital discharge. It included all medical patients in Internal Medicine, Pneumology and Oncology Departments. The patient's thromboembolic risk and type of thromboembolism prophylaxis indication during hospitalization and after discharge were determined. Results. A total of 116 patients (52 in Internal Medicine Department, 35 in Pneumology Department and 29 in Oncology Department), with a mean age of 67 ± 17 years (35 females; 81 males) were included. During hospitalization, 62.9% of the patients had a high risk of thromboembolic events, 3.4% a moderate risk, 23.3% low risk, and 10.3% had no risk. After discharge, these proportions were 35.6%, 3.8%, 24% and 34.6%, respectively. A total of 49.1% of the patients had an adequate indication of venous thromboembolism prophylaxis during the hospitalization and after discharge (AU)
