Pharmacokinetics differences of propofol during different pathological stages of severe burn in rabbits / 中华烧伤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the characteristics and differences of propofol pharmacokinetics in shock phase and hypermetabolic phase in severe burn in rabbits.</p><p><b>METHODS</b>Twenty New Zealand rabbits were assigned to burn group (n = 10) and sham injury group (n = 10) according to the random number table. Rabbits in burn group were inflicted with 30%TBSA full-thickness scald (named burn below), resuscitated instantly, and were intravenously injected with 5.1 mg/kg propofol 6 hours after injury. 1.5 mL blood was collected from left external jugular vein at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90 minute(s) after injection respectively. Above procedure was performed again 1 week later. Rabbits in sham injury group were treated similarly as rabbits in burn group but were sham scalded. Propofol concentration in plasma was determined with high performance liquid chromatography. Data of propofol concentration-time were analyzed with 3P97 practical pharmacokinetics calculating program, and then the most fit compartment model was selected to calculate pharmacokinetic parameters.</p><p><b>RESULTS</b>The blood concentration-time curve of propofol fitted in with the two-compartment model in burn group, and three-compartment model in sham injury group. During shock phase, comparing with central compartment distribution volume [Vc, (3.1 + or - 1.5) L/kg], area under curve [AUC, (25 + or - 7) mg x min x L(-1)], elimination phase half life [t1/2beta, (113 + or - 93) min], clearance [CLs, (110 + or - 50) mL x kg(-1) x min(-1)] of rabbits in sham injury group, Vc[(8.8 + or - 4.2) L x kg(-1)] and AUC [(44 + or - 10) mg x min x L(-1)] increased significantly (with t value respectively 3.191 and 3.668, and P values both below 0.01); t1/2beta [(339 + or - 258) min] prolonged (t = 2.932, P < 0.05); CLs [(40 + or - 30) mL x kg(-1) x min(-1)] decreased (t = -3.013, P < 0.05) in burn group. During hypermetabolic phase, CLs [(180 + or - 40) mL x kg(-1) x min(-1)] of rabbits in burn group was significantly higher than that in sham injury group [(90 + or - 30) mL x kg(-1) x min(-1), t = -3.013, P < 0.05]. Comparing with those of rabbits in burn group during shock phase, Vc [(4.1 + or - 1.3) L/g] and AUC [(24 + or - 5) mg x min x L(-1)] decreased significantly (with t value respectively 2.979 and 3.766, and P value both below 0.01); distribution phase half time [t1/2alpha, shock phase (16.1 + or - 13.1) min and hypermetabolic phase (8.3 + or - 2.5) min] and t1/2beta [(55 + or - 19) min] shortened obviously (with t value respectively 9.065 and 8.795, and P values both below 0.01); CLs increased significantly (t = 4.238, P < 0.01) during hypermetabolic phase.</p><p><b>CONCLUSIONS</b>There are great differences in propofol pharmacokinetics between shock phase and hypermetabolic phase in severely burned rabbits. The change is characterized by increase in Vc and AUC, extension of t1/2alpha and t1/2beta, decrease in CLs during shock phase and obvious increase of CLs during hypermetabolic phase.</p>