Abstract
Propofol is rapidly cleared from the body by biotransformation; however, the repercussions of changes in cytochrome P-450 activity on propofol rate of elimination are unknown. To assess how changes in cytochrome P-450 activity affect propofol kinetics, one group of rabbits (N = 6) was pretreated with cimetidine, another (N = 6) had an inflammatory reaction produced by the subcutaneous injection of turpentine, and a third one (N = 6) was subjected to mild hypoxia. Propofol was infused (0.3 mg/min/kg) for 40 min; multiple blood samples were withdrawn before and once the infusion was stopped to assess propofol blood kinetics. Cimetidine did not modify propofol kinetics. An inflammatory reaction prolonged propofol half-life without changing significantly its clearance or volume of distribution. Hypoxia decreased propofol clearance and as a consequence, its half-life increased. Parallel studies were conducted in vitro, where propofol metabolism was documented in liver and lung homogenates prepared from controls (N = 6), and from rabbits that were pretreated with cimetidine (N = 3), had an inflammatory reaction (N = 5), or were hypoxic (N = 6). In controls, the lung biotransformed propofol as rapidly as the liver, and both organs generated an unidentified polar metabolite. Cimetidine did not affect the in vitro metabolism of propofol. The inflammatory reaction reduced the in vitro rate of elimination of propofol and, as a consequence, the production rate of the metabolite was also decreased in liver and lung homogenates. Hypoxia diminished hepatic metabolism of propofol but did not influence that in lung homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|