Assuntos
Biomarcadores Tumorais/genética , Neoplasias/tratamento farmacológico , Neoplasias/economia , Medicina de Precisão/economia , Mecanismo de Reembolso/economia , Biomarcadores Tumorais/metabolismo , Análise Custo-Benefício , Acessibilidade aos Serviços de Saúde/economia , Humanos , Técnicas de Diagnóstico Molecular/economia , Terapia de Alvo Molecular/economia , Neoplasias/classificação , Neoplasias/genética , Países Baixos , Taxa de SobrevidaAssuntos
Neoplasias Encefálicas/diagnóstico por imagem , Cisto Dermoide/diagnóstico por imagem , Transtornos Mentais/diagnóstico por imagem , Estado Epiléptico/diagnóstico por imagem , Neoplasias Encefálicas/complicações , Cisto Dermoide/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Estado Epiléptico/etiologia , Tomografia Computadorizada por Raios XAssuntos
Neoplasias Encefálicas/complicações , Cisto Dermoide/complicações , Estado Epiléptico/etiologia , Neoplasias Encefálicas/diagnóstico por imagem , Calcinose , Cisto Dermoide/diagnóstico por imagem , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea , Tomografia Computadorizada por Raios XAssuntos
Hexobarbital/sangue , Animais , Cromatografia Gasosa , Cinética , Masculino , Ratos , Ratos Endogâmicos , EstereoisomerismoRESUMO
1 The effects of sex and oral contraceptives (OC) on the disposition of oral nitrazepam were studied in six healthy young males, in six healthy young females in the follicular and luteal phase of the menstrual cycle and in six healthy young females using OC-steroids in two stages of the pill cycle. 2 There was no influence of the menstrual cycle on the pharmacokinetic parameters of nitrazepam, nor was there a significant difference between these parameters in males and females in either phase of the cycle. The elimination half-life was 27.3 +/- 1.3 h in males, 27.7 +/- 1.5 h in females in the follicular phase and 29.6 +/- 1.4 h in the luteal phase of the menstrual cycle. Total plasma clearance was 59.3 +/- 2.7 ml/min, 58.2 +/- 3.3 and 55.8 +/- 5.0 ml/min respectively. 3 The use of OC-steroids did not significantly alter the elimination half-life of nitrazepam: 30.6 +/- 2.3 and 31.2 +/- 2.2 h in the first and second half of the pill cycle. The total nitrazepam clearance in these females (46.6 +/- 4.6 and 45.6 +/- 4.1 ml/min) was significantly lower than in males (P less than 0.05). 4 The protein unbound fraction of nitrazepam was progressively higher going from males (11.4 +/- 0.1%) to females in the luteal phase of the cycle (12.4 +/- 0.5%) to females using OC-steroids (13.5 +/- 0.4%). Only the difference between males and females using OC-steroids was statistically significant. 5 The clearance calculated relative to the unbound drug (intrinsic clearance) was significantly decreased in females taking OC-steroids as compared to males and females not taking them (Cli = 323 +/- 30 ml/min in females using OC-steroids, 530 +/- 37 ml/min in males and 459 +/- 40 ml/min in females). 6 The results of this study are not likely to have important consequences for dosage of nitrazepam as an hypnotic. The most pronounced effect observed was inhibition of nitrazepam clearance and especially intrinsic clearance by OC-steroids. Females on OC-steroids taking a nitrazepam tablet every evening, will have highly steady levels of nitrazepam (and certainly of unbound nitrazepam) than males or females not taking OC-steroids.