Farmacokinetiek en farmacodynamiek van propofol bij morbide obese patiënten

BACKGROUND AND OBJECTIVES In view of the increasing prevalence of morbidly obese patients, in this study the influence of excessive bodyweight on the pharmacokinetics and pharmacodynamics of propofol is characterized using bispectral index values as pharmacodynamic endpoint. DESIGN AND METHODS A population pharmacokinetic model was developed using the nonlinear mixed-effects modelling software NONMEM VI, on the basis of 491 blood samples from 20 morbidly obese patients (total body weight range 98-167 kg) and on previously published data (725 blood samples) from 44 lean patients (total body weight range 55-98 kg). For the population pharmacodynamic analysis, 2246 bispectral index values of 20 morbidly obese patients were available. RESULTS In a three-compartment pharmacokinetic model, total body weight (TBW) proved to be the most predictive covariate for clearance (CL) in 20 morbidly obese patients [CL = 2.33×(TBW/70) ^0.72 L/min]. Similar results were obtained when morbidly obese patients and 44 lean patients were analyzed together [CL = 2.22×(TBW/70) ^0.67 L/min]. No covariates were identified for other pharmacokinetic parameters. Depth of anaesthesia in morbidly obese patients was adequately described by a two-compartment biophase distribution model with a sigmoid E _max pharmacodynamic model (EC50 = 2.12 mg/L) without covariates. CONCLUSION We developed a pharmacokinetic and pharmacodynamic model for propofol in morbidly obese patients in which total body weight proved to be the major determinant for clearance using an allometric function with an exponent of 0.72. For the other pharmacokinetic and pharmacodynamic parameters, no covariates could be identified.