The 3<sup>rd</sup> International Conference on Drug Discovery & Therapy: Dubai, February 7 - 11, 2011

Drug Metabolism (Track)



On the oxidative metabolism of propofol (2,6-Diisopropylphenol) in pig and she

L. Dibbelt
Germany

Abstract:

Background: Propofol (2,6-diisopropylphenol) is an intravenous narcotic frequently applied for induction and maintenance of anaesthesia. It is known to be metabolized predominantly by conjugation. To study the importance of the oxidative metabolism of propofol, we compared the plasma concentrations of the narcotic and its quinone during propofol anaesthesia in two mammalian species.

Methods: During routine anaesthesia with continuous and bolus infusion of propofol (Disoprivan®, Astra Zeneca) in 6 pigs and 6 sheep, heparinized blood was taken at 30 and 12 time points, respectively. Following extraction of the plasma, propofol was determined by reversed phase HPLC with fluorescence detection, while propofol quinone was analyzed by normal phase HPLC with UV detection.

Results: Continuous infusion of propofol at 1 mg kg-1 h-1 spiked with boli of 4 mg kg-1 resulted in similar peak plasma concentrations of propofol (4 - 9 mg/l in pigs, 3 - 8 mg/l in sheep). Peak plasma concentrations of propofol quinone, however, differed markedly between both species (0.05 - 0.19 mg/l in pigs, 1 - 4 mg/l in sheep).

Conclusion: Oxidation of propofol to its quinone is a quantitatively insignificant metabolic pathway in pigs but is highly active in sheep.

Keywords: Propofol, propofol quinone, HPLC, plasma concentrations