Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery

Abstract

Available propofol pharmacokinetic protocols for target-controlled infusion (TCI) were obtained from healthy individuals. However, the disposition as well as the response to a given drug may be altered in clinical conditions. The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol during total intravenous anesthesia (propofol/fentanyl) monitored by bispectral index (BIS) in patients scheduled for abdominal aortic surgery. Population nonlinear mixed-effect modeling was done with Nonmem. Data were obtained from ten male patients. The TCI system (Diprifusor) was used to administer propofol. The BIS index served to monitor the depth of anesthesia. The propofol dosing was adjusted to keep BIS level between 40 and 60. A two-compartment model was used to describe propofol PK. The typical values of the central and peripheral volume of distribution, and the metabolic and inter-compartmental clearance were V(C) = 24.7 l, V(T) = 112 l, Cl = 2.64 l/min and Q = 0.989 l/min. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment with the rate constant for the distribution to the effector compartment equal to 0.240 min(-1). The BIS index was linked to the effect site concentrations through a sigmoidal E(max) model with EC(50) = 2.19 mg/l. The body weight, age, blood pressure and gender were not identified as statistically significant covariates for all PK/PD parameters. The population PK/PD model was successfully developed to describe the time course and variability of propofol concentration and BIS index in patients undergoing surgery.

Pharmacokinetics and pharmacodynamics of propofol in cancer patients undergoing major lung surgery

“…The clearance of propofol observed in this study was also slightly larger than in other studies available in the literature including both healthy individuals as well as ASA I–III patients scheduled for laparoscopic cholecystectomy [2, 8, 11, 27, 29–32]. Occasionally, even higher clearances have been observed for ASA III patients undergoing aortic surgery (2.64 L/min) [33]. This suggests that PK of propofol has not been fully understood in all clinical situations, and further research is necessary to indentify all the mechanisms that underlie the observed differences.…”

Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction

“…2C) and indicates that MO subjects in our study had greater CNS sensitivity to propofol. A decreased EC 50 value for propofol was also previously noted in patients undergoing abdominal aortic surgery (Wiczling et al, 2012). However, the exact reasons why MO subjects were more sensitive to the anesthetic effects remain unknown.…”

“…Therefore, our study provides a mechanistic PK/PD explanation as to why dose reduction was required in MO subjects. In addition, our study and a study by Wiczling et al (2012) highlight that determining the pharmacodynamic parameters is essential to fully assess the effects of diseases on clinical responses of propofol.…”

“…Propofol PK is generally described by a two-compartment (Peeters et al, 2008a;Bienert et al, 2010;Wiczling et al, 2012) or three-compartment (Schnider et al, 1998;van Kralingen et al, 2011) model. Selection of the best model seems to depend on the duration of blood collection, sampling frequency, and manner of administration (e.g., bolus or infusion) (Wiczling et al, 2012).…”

Abordagem PK-PD do propofol na revascularização do miocárdio para estudo da influência da circulação extracorpórea na ligação às proteínas plasmáticas e no efeito hipnótico

“…Com relação à escolha do modelo farmacocinético, reportou-se anteriormente que o modelo aberto de dois compartimentos foi utilizado por diversos pesquisadores para o estudo da farmacocinética do propofol em grandes cirurgias como a cirurgia de abdome superior pela investigação da fase de distribuição (alfa) e de eliminação (beta) (WICZLING et al, 2012). Reportou-se que a distribuição rápida do propofol é justificada pela imediata instalação de efeito (1 a 3 minutos) a partir do início da infusão venosa contínua alvo controlada (ADAM et al, 1983;COCKSHOTT et al, 1992;KNIBBE et al, 2002;METS, 2000;SCHUTTLER et al, 1988).…”