Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência

Ricardo Francisco Simoni; Luis Otávio Esteves; Luiz Eduardo de Paula Gomes Miziara; Luiz Marciano Cangiani; Gustavo Groth Oliveira Alves; André Luz Pereira Romano; Paula Úrica Hansen; Pedro Thadeu Galvão Vianna

doi:10.1590/S0034-70942011000400002

Scientific Article

Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência

Clinical evaluation of two ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness

Ricardo Francisco Simoni; Luis Otávio Esteves; Luiz Eduardo de Paula Gomes Miziara; Luiz Marciano Cangiani; Gustavo Groth Oliveira Alves; André Luz Pereira Romano; Paula Úrica Hansen; Pedro Thadeu Galvão Vianna

http://dx.doi.org/10.1590/S0034-70942011000400002 Braz J Anesthesiol, vol.61, n4, p.402-408, 2011

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JUSTIFICATIVA E OBJETIVOS: A constante de equilíbrio entre o plasma e o sítio efetor (ke0) é utilizada pelos modelos farmacocinéticos para prever a concentração do fármaco em seu local de ação (Ce). Seria interessante que a Ce de propofol fosse semelhante na perda e na recuperação da consciência. O objetivo deste estudo foi avaliar o desempenho clínico de duas diferentes ke0 (rápida = 1,21 min-1 e lenta = 0,26 min-1) com relação à Ce durante a perda e a recuperação da consciência, usando o modelo farmacocinético de Marsh. MÉTODO: Participaram deste estudo 20 voluntários adultos sadios do sexo masculino. Em todos os voluntários, administrou-se propofol em regime de infusão alvo-controlada, modelo farmacocinético de Marsh ke0 rápida e, em outra oportunidade, usou-se o mesmo modelo farmacocinético com a ke0 lenta. Inicialmente, o propofol foi infundido em concentração-alvo plasmática de 3,0µg.mL-1. A perda de consciência e a recuperação de consciência basearam-se na resposta ao estímulo verbal. A Ce foi anotada no momento da perda e da recuperação da consciência. RESULTADOS: Na perda e na recuperação da consciência a Ce pela ke0 rápida foi diferente (3,64 ± 0,78 e 1,47 ± 0,29µg.mL-1, respectivamente, p < 0,0001), enquanto com a ke0 lenta a Ce foi semelhante (2,20 ± 0,70 e 2,13 ± 0,43µg.mL-1, respectivamente, p = 0,5425). CONCLUSÕES: Do ponto de vista clínico, a ke0 lenta (0,26 min-1) incorporada ao modelo farmacocinético de Marsh apresentou melhor desempenho que a ke0 rápida (1,21 min-1), uma vez que a concentração de propofol prevista em seu local de ação na perda e recuperação da consciência foi semelhante.

Palavras-chave

ANESTÉSICOS, Venoso, FARMACOLOGIA, EQUIPAMENTOS, Bomba de Infusão

Abstract

BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min-1, and slow = 0.26 min-1) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL-1. Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL-1, respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL-1, respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min-1) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min-1), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

Keywords

Pharmacokinetics, Propofol, administration and dosage, Intraoperative Awareness, Drug Delivery Systems

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Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência

Clinical evaluation of two ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness

Ricardo Francisco Simoni; Luis Otávio Esteves; Luiz Eduardo de Paula Gomes Miziara; Luiz Marciano Cangiani; Gustavo Groth Oliveira Alves; André Luz Pereira Romano; Paula Úrica Hansen; Pedro Thadeu Galvão Vianna

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