Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia

Abstract

Background. The aims of this study were to investigate the effectiveness, safety, pharmacokinetics, and pharmacodynamics of microemulsion propofol, Aquafol™ (Daewon Pharmaceutical Co., Ltd, Seoul, Republic of Korea). Methods. In total, 288 patients were randomized to receive 1% Aquafol™ or 1% Diprivan® (AstraZeneca, London, UK) (n=144, respectively). A 30 mg test dose of propofol was administered i.v. over 2 s for assessing injection pain. Subsequently, a bolus of propofol 2 mg kg-1 (-30 mg) was administered. Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil. Mean infusion rates of both formulations and times to loss of consciousness (LOC) and recovery of consciousness (ROC) were recorded. Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated. Results. Mean infusion rate of Aquafol™ was not statistically different from that of Diprivan® (median: 6.2 vs 6.3 mg kg-1 h-1). Times to LOC and ROC were slightly prolonged in Aquafol™ (median: 21 vs 18 s, 12.3 vs 10.8 min). Aquafol™ showed similar incidence of adverse events to Diprivan®. Aquafol™ (vs Diprivan®) caused more severe (median VAS: 72.0 vs 11.5 mm) and frequent (81.9 vs 29.2%) injection pain. The dose-normalized AUClast of Aquafol™ and Diprivan® was 0.71 (0.19) and 0.74 (0.20) min litre-1. The V1 of both formulations were proportional to lean body mass. Sex was a significant covariate for k12 and Ce50 of Aquafol™, and for ke0 of Diprivan®. Conclusions. Aquafol™ was as effective and safe as Diprivan®, but caused more severe and frequent injection pain. Aquafol™ demonstrated similar pharmacokinetics to Diprivan®. © The Author [2010].