IDENTIFICATION OF A GENETIC DEFECT RESPONSIBLE FOR THE POLYMORPHISM OF PROPOFOL METABOLISM

Abstract

S352 INTRODUCTION: Glucuronic acid conjugation is the major metabolism of propofol whereas both conjugation of its ringhydroxylated derivative with glucuronic acid and sulphate are minor metabolic pathways of propofol, which need preliminary hydroxylation at the C4 posotion. Although cytochrome (CYP)-dependent monooxygenases are responsible for this biotransformation, the major CYP isoforms has not been identified. In this paper we reported delayed emergence from propofol anesthesia in two patients, who exhibited genetic polymorphism of CYP2C19. CASES: A 35-yr-old man who underwent internal fixation of tibial fracture was anesthetized by continuous infusion of propofol under epidural anesthesia. It took 35 minutes for his emergence from propofol. A 38-yr-old man who underwent lower leg amputation due to osteosarcoma was anesthetized by propofol with nitrous oxide under epidural anesthesia. It took 33 minutes for his emergence from propofol. Both patients exhibited a guanine to adenine point mutation in exon5 of CYP2C19, which produced an aberrant splice site and a truncated nonfunctional protein. DISCUSSION AND CONCLUSION: Recently, Guitton et al showed that part of the propofol hydroxylase activity was mediated by CYP2C9 in vitro. However, propofol was likely to be metabolized by additional isoforms such as CYP2A6, 2C8, 2C18, 2C19 and 1A2. Although the activity of CYP2C9 and the expression rates of these specific isoforms in the microsomal fraction of two patients were unknown, genetic defect of CYP2C19 could be responsible for delayed emergence from propofol anesthesia.