ABSTRACT
The growing interest in marine natural substances as potential new drugs has made total synthesis a real asset for structure confirmation. Trichormamide C (1), a cyclic lipopeptide isolated from the cyanobacteria Oscillatoria sp., is characterized by the presence of nonproteinogenic amino acids in the sequence. Trichormamide C structural confirmation was carried out through the implementation of a flexible synthesis resulting in two new analogs (3 and 4).
ABSTRACT
AIMS: A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. METHODS: A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.
Subject(s)
Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP3A/genetics , Indans/pharmacokinetics , NADPH-Ferrihemoprotein Reductase/genetics , Piperidines/pharmacokinetics , Receptors, Steroid/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Aged , Aged, 80 and over , Alleles , Cross-Sectional Studies , Donepezil , Female , Genotype , Humans , Indans/adverse effects , Male , Middle Aged , Models, Biological , Piperidines/adverse effects , Pregnane X ReceptorABSTRACT
A Organização Mundial da Saúde (OMS) e a Seção de Psiquiatria da Pessoa Idosa da Associação Mundial de Psiquiatria (AMP), em colaboração com um grupo interdisciplinar de representantes das principais associações internacionais e organizações não-governamentais implicadas na saúde mental das pessoas idosas, publicaram três declarações técnicas de consenso sobre a psiquiatria da pessoa idosa (1), a organização dos cuidados em psiquiatria da pessoa idosa (2) e o ensino da psiquiatria da pessoa idosa (3). O Dia Mundial da Saúde 2001, cujo tema foi "Não à exclusão, sim aos cuidados", deu origem a uma nova reunião de consenso sobre o tema da estigmatização e discriminação das pessoas idosas com transtornos mentais. Essa nova reunião foi realizada em Lausanne nos dias 8 e 9 de outubro de 2001 e produziu uma declaração técnica de consenso. O texto inicial foi publicado pela OMS e AMP em inglês. Este artigo apresenta a versão em português desse documento.
This technical consensus statement is jointly produced by the Old Age Psychiatry section of the World Psychiatric Association and the World Health Organization, with the collaboration of several NGOs and the participation of experts from different regions. It is intended to be a tool for (i) promoting debate at all levels on the stigmatization of older people with mental disorders; (ii) outlining the nature, causes and consequences of this stigmatization; and (iii) promoting and suggesting policies, programs and actions to combat this stigmatization.
Subject(s)
Humans , Aged , Consensus Development Conferences as Topic , Geriatric Psychiatry , Mental Disorders/psychology , Stereotyping , Aged/psychology , Prejudice , Mental Health , Health of the ElderlyABSTRACT
This technical consensus statement is jointly produced by the Old Age Psychiatry section of the World Psychiatric Association and the World Health Organization, with the collaboration of several NGOs and the participation of experts from different Regions. It is intended to be a tool for (i) promoting debate at all levels on the stigmatisation of older people with mental disorders; (ii) outlining the nature, causes and consequences of this stigmatisation; and (iii) promoting and suggesting policies, programmes and actions to combat this stigmatisation.
Subject(s)
Mental Disorders/psychology , Prejudice , Stereotyping , Aged , Attitude to Health , Health Education , Health Policy , Health Services for the Aged/standards , Humans , Mental Disorders/therapy , Mental Health Services/standards , Public OpinionABSTRACT
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