DISPOSITION AND RENAL CLEARANCE OF PROPOFOL AND ITS GLUCURONIDE METABOLITES AFTER A SHORT INTRAVENOUS-INFUSION OF PROPOFOL

The aim of this study was to investigate the disposition kinetics and renal clearance of propofol (2,6-di-isopropylphenol) and its metabolit es (propofol-glucuronide and 1,4-quinolconjugate) in surgical patients after a short-duration infusion (30 minutes). Two half-life (t 1/2) v alues could be distinguished in the elimination of propofol and each o f its metabolites. The distribution half-life (t (1/2 alpha)) differed significantly from the elimination half-life (t (1/2 beta)) [7.6 +/- 3.3 minutes and 119 +/- 30.7 minutes, respectively; p = 0.0003]. The c alculated t (1/2 alpha) and t (1/2 beta) values for each metabolite di ffered significantly (for propofolglucuronide, p = 0.0017; and for 1,4 -quinolconjugate p = 0.0185). The apparent t(1/2absorption) of both me tabolites was similar and reflected the t(1/2formation) (80 vs 59 minu tes, respectively). The volumes of distribution of propofol in the cen tral compartment (V-1; 34.4 +/- 12.01,) differed from the volume of di stribution in the second compartment (V-beta) [511 +/- 355L, p = 0.000 7]. The total body clearance of propofol was 2.08 +/- 1.00 L/min. The maximum plasma concentrations (C-max) of propofolglucuronide and 1,4-q uinolconjugate were 4.7 +/- 1.8 mg/L and 1.2 +/- 0.4 mg/L, respectivel y (p = 0.0363). The main compound in plasma was propofolglucuronide, i ts AUC accounting for 75 % of the total AUC of all compounds; propofol itself contributed 9.6% and the 1,4-quinolconjugate contributed 14.9% . The renal clearance of propofolglucuronide was significantly smaller (114 +/- 95 ml/min) than that of the 1,4-quinolconjugate (339 +/- 247 ml/min; p = 0.0156). The percentages of propofolglucuronide (34.4 +/- 9.5%) and 1,4-quinolconjugate (17.8 +/- 5.0%) excreted in the urine w ere significantly different (p = 0.0156). No free propofol was excrete d in the urine.