Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model

Abstract

Background. The objective of this study was to develop a pharmacokinetic (PK) model to characterize the influence of obesity on propofol PK parameters. Methods. Nineteen obese ASA II patients undergoing bariatric surgery were studied. Patients received propofol 2 mg kg21 bolus dose followed by a 5–20–40–120 min, 10–8–6–5 mg kg21 h21 infusion. Arterial blood samples were withdrawn at 1, 3, 5 min after induction, every 10–20 min during propofol infusion, and every 10–30 min for 2 h after stopping the propofol infusion. Arterial samples were processed by highperformance liquid chromatography. Time–concentration data profiles from this study were pooled with data from two other propofol PK studies available at http://www .opentci.org. Population PK modelling was performed using non-linear mixed effects model. Results. The study involved 19 obese adults who contributed 163 observations. The pooled analysis involved 51 patients (weight 93 SD 24 kg, range 44–160 kg; age 46 SD 16 yr, range 25–81 yr; BMI 33 SD 9 kgm22, range 16–52 kg m22). A three-compartment model was used to investigate propofol PK. An allometric size model using total body weight (TBW) was superior to all other models investigated (linear TBW, free fat mass, lean body weight, normal fat mass) for all clearance parameters. Variability in V2 and Q2 was reduced by a function showing a decrease in both parameters with age. Conclusions. We have derived a population PK model using obese and non-obese data to characterize propofol PK over a wide range of body weights. An allometric model using TBW as the size descriptor of volumes and clearances was superior to other size descriptors to characterize propofol PK in obese patients.