Influence of 20% Lipid Emulsion on Drug Concentration, Distribution Volume and Pharmacology Effect of Continuous Infusion of Propofol in Rabbits

Objective To investigate the influence of 20% lipid emulsion on drug plasma concentration, distribution volume and pharmacology effect of propofol administered with constant rate intravenous infusion in rabbits. Methods Propofol was intravenously administrated at a constant rate of 70 mg/(kg·h) in propofol group(P group, n=8),low rate lipid group (L group, n=8),high rate lipid group (H group,n=8) and saline group(S group, n=8) within 2 h. After 60 min, different agents were administrated in L group 20% lipid emulsion with rate of 0.3 mL/(kg·h),H group 20% lipid emulsion with rate of 15 mL/(kg·h),S group saline with rate of 15 mL/(kg·h) for another 60 min respectively. Blood samples were taken to measure the plasma concentration and calculate the pharmacokinetic parameters at the following time points:30,60,65,70,80,90,120 min after the start of propofol infusion and 10,20,30,60,120,180 min after the termination of propofol infusion. Brain tissues were also taken to measure propofol concentration. Related information about vital signs and pharmaceutical effects were recorded. Results High rate lipid infusion was associated with elevated propofol plasma concentration and reduced volume of distribution. The volume of distribution based on the terminal phase (V):P group,(34.56±16.11) mL;L group,(33.37±29.87) mL;H group,(7.29±3.20) mL;S group,(35.46±13.58) mL;P<0.05). The volume of distribution at steady state(V_ss):P group,(11.13±3.21) mL;L group,(13.87±4.09) mL;H group,(4.82±1.46) mL;S group,(11.61±4.11) mL;P<0.05). Painful stimulation existences were higher at 90,120 min and the mean arterial pressure and heart rate were higher in H group (P<0.05). The propofol concentration in brain tissue was lower in H group at 120 min (P<0.05). Conclusion Amelioration of pharmacology effect of propofol with high rate lipid infusion is associated with reduced V,V_ss,elevated propofol plasma concentration and lowered propofol brain tissue concentration. 20% lipid will not influence these indice when infused with low rate, indicating that lipid in TPN will not change the sedation effects of propofol.