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Impacto das características intra- e inter-individuais na farmacocinética dos fármacos
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| 1.56 MB | Adobe PDF |
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Abstract(s)
A variabilidade individual é um fator determinante na resposta farmacológica. Por isso, compreender os diversos fatores inter -e intra-individuais é fundamental para a otimização da terapêutica, maximizando a eficácia e minimizando dos efeitos adversos. A monitorização terapêutica é essencial para avaliar o comportamento do fármaco num indivíduo específico, visando a individualização da terapêutica e deste modo tratar o doente e não a doença.
Neste contexto, a presente monografia procura analisar a influência das características individuais na farmacocinética dos fármacos. Para tal, é descrito o ciclo geral do medicamento, discutindo qual o impacto de fatores, como o fluxo sanguíneo, o tempo de contacto e a ligação às proteínas plasmáticas nas etapas da absorção, distribuição, metabolismo e excreção (ADME). O objetivo principal desta revisão bibliográfica consistiu em demonstrar o impacto clínico que fatores inter-individuais como a idade, o género, a genética e o peso corporal, assim como fatores intra-individuais, nomeadamente a alimentação, o estado clínico do indivíduo, a condição de gravidez e a administração concomitante de medicação apresentam no sistema ADME dos fármacos. Dentro do estado clínico, destacou-se a insuficiência cardíaca, doença de crohn, doença renal crónica, doença hepática e a situação clínica particular dos indivíduos queimados. Todos estes fatores demonstraram interferir na farmacocinética dos fármacos, sendo uns mais impactantes que outros.
Através de estudos farmacocinéticos onde se recorre à simulação de alterações fisiológicas, é possível concluir sobre a necessidade de alterar os regimes posológicos em função das características individuais. A maioria dos estudos concluem que a farmacocinética é teoricamente afetada, mas ainda existem poucas evidências clínicas que indiquem necessidade de redução ou aumento da dose. A idade, o estado clínico e a genética constituem fatores de variabilidade com um peso crescente na área da farmácia clínica e é essencial perceber os ajustes necessários a implementar para garantir resultados terapêuticos positivos. Tendo em vista estes aspetos, a área da farmacocinética clínica é imprescindível para o estabelecimento e terapêuticas farmacológicas individualizadas
Individual variability is a determining factor in pharmacological response. Therefore, understanding the various inter- and intra-individual factors is essential for optimizing therapy, maximizing effectiveness and minimizing adverse effects. Therapeutic monitoring is essential to evaluate the behavior of the drug in a specific individual, aiming to individualize therapy and thus treat the patient and not the disease. In this context, this monograph seeks to analyze the influence of individual characteristics on the pharmacokinetics of drugs. To this end, the general cycle of the medicine is described, discussing the impact of factors such as blood flow, contact time and binding to plasma proteins on the stages of absorption, distribution, metabolism and excretion (ADME). The main objective of this literature review was to demonstrate the clinical impact that inter-individual factors such as age, gender, genetics and body weight, as well as intra-individual factors, namely diet, the individual's clinical status, condition of pregnancy and concomitant administration of medication present in the ADME drug system. Within the clinical status, cardiac insufficiency, Crohn's disease, chronic kidney disease, liver disease and the particular clinical situation of burned individuals stood out. All of these factors have been shown to interfere with the pharmacokinetics of drugs, some being more impactful than others. Through pharmacokinetic studies using the simulation of physiological changes, it is possible to conclude on the need to change dosage regimes depending on individual characteristics. Most studies conclude that pharmacokinetics are theoretically affected, but there is still little clinical evidence to indicate the need for dose reduction or increase. Age, clinical status and genetics are factors of variability with increasing importance in clinical pharmacy and it is essential to understand the necessary adjustments to implement to guarantee positive therapeutic results. In view of these aspects, the area of clinical pharmacokinetics is essential for the establishment of individualized pharmacological therapies.
Individual variability is a determining factor in pharmacological response. Therefore, understanding the various inter- and intra-individual factors is essential for optimizing therapy, maximizing effectiveness and minimizing adverse effects. Therapeutic monitoring is essential to evaluate the behavior of the drug in a specific individual, aiming to individualize therapy and thus treat the patient and not the disease. In this context, this monograph seeks to analyze the influence of individual characteristics on the pharmacokinetics of drugs. To this end, the general cycle of the medicine is described, discussing the impact of factors such as blood flow, contact time and binding to plasma proteins on the stages of absorption, distribution, metabolism and excretion (ADME). The main objective of this literature review was to demonstrate the clinical impact that inter-individual factors such as age, gender, genetics and body weight, as well as intra-individual factors, namely diet, the individual's clinical status, condition of pregnancy and concomitant administration of medication present in the ADME drug system. Within the clinical status, cardiac insufficiency, Crohn's disease, chronic kidney disease, liver disease and the particular clinical situation of burned individuals stood out. All of these factors have been shown to interfere with the pharmacokinetics of drugs, some being more impactful than others. Through pharmacokinetic studies using the simulation of physiological changes, it is possible to conclude on the need to change dosage regimes depending on individual characteristics. Most studies conclude that pharmacokinetics are theoretically affected, but there is still little clinical evidence to indicate the need for dose reduction or increase. Age, clinical status and genetics are factors of variability with increasing importance in clinical pharmacy and it is essential to understand the necessary adjustments to implement to guarantee positive therapeutic results. In view of these aspects, the area of clinical pharmacokinetics is essential for the establishment of individualized pharmacological therapies.
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Keywords
Farmacocinética Farmacocinética clínica Variabilidade intra e inter-individual Sistema ADME