Propofol in a modified cyclodextrin formulation: first human study of dose-response with emphasis on injection pain.

Abstract

A new lipid-free preparation of propofol has been developed containing the drug, sulfobutylether ß-cyclodextrin and water. The primary objective of this study was to compare the effects of propofol in the lipid formulation with those of the new cyclodextrin formulation, particularly with regard to pain on injection. We hypothesized that the propofol in cyclodextrin would be associated with less pain on injection than propofol in lipid. The study was a single-center, double-blind, 2-period, randomized, dose-escalating study using a completely balanced cross-over design in healthy volunteers. Pain on injection was compared between propofol in cyclodextrin and propofol in lipid using subject and observer assessments of pain rated at several different time points. Five response variables to pain were analyzed. Propofol in cyclodextrin had significantly higher pain scores for all 5 variables. Other endpoints, including sedation, showed no difference. The propofol in cyclodextrin formulation failed to reduce the pain on injection associated with propofol.