title: Clinical evaluation of two Ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness.
abstract: 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.
authors: Faculdade de Medicina de Botucatu, UNESP, Brazil.
authors: Ricardo Francisco
authors: RF
authors: Simoni
authors: Luis Otávio
authors: LO
authors: Esteves
authors: Luiz Eduardo de Paula Gomes
authors: LE
authors: Miziara
authors: Luiz Marciano
authors: LM
authors: Cangiani
authors: Gustavo Groth Oliveira
authors: GG
authors: Alves
authors: André Luz Pereira
authors: AL
authors: Romano
authors: Paula Úrica
authors: PÚ
authors: Hansen
authors: Pedro Thadeu Galvão
authors: PT
authors: Vianna
mesh_terms: D000328:Adult; D003243:Consciousness / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000493:pharmacokinetics*
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol