Pharmacokinetic Studies And Tissue Distribution Of Propofol

Objective:A high performance liquid chromatograph with fluoresce- ence detection (HPLC-FLD) method for analyzing the concentration of propofol in biological sample was established. And the aim of this study was to compare the pharmacokinetics (PK) parameters and tissue distribution of propofol microemulsion injection with propofol emulsion injection.Methods:Chromatography method:The HPLC system consisted of water--methanol (25:75) as mobile phase with the flow rate of 1.0 ml/min, and the detection wavelength was Ex:276nm, Em:310nm, Column tempetature was 30℃. Animal test method:(1)Bioequivalence:12 Beagle dogs were randomly divided into two groups, giving single-dose propofol respectively by intravenous In I andII stage, and measured blood plasma concentration at different time. (2) Pharmacokinetics:12 Beagle dogs were randomly divided into three groups whith large,medium and small doses, and using 3-cycle cross-administration and blood. (3)Tissue distribution:36 SD rats were randomly divided into two groups with test preparation and reference preparation, and each group was randomly divided into three groups with istribution phase, balance phase and elimination phase, intravenous administration by the capacity of 0.125ml/100g, and execute the rats at the time point of 5, 30, 120 min, cut appropriate organizations in the same location to determine the content.Results: Under these chromatographic conditions described above, propofol was well separated . The lower limit of quantitation (LLOQ) was 0.01μg/ml. The mean recovery of plasma samples was 77%～83%. The mean recover of tissue samples ranged from 91% to 109% .The relative standard deviation (RSD) of inter-day andintra-day were all less than 15%. Bioequivalence:AUC(0～T) of test preparation and reference preparation were 27.67±9.60 and 21.90±10.10(μg/ml)·min, propofol microemulsion and Propofol emulsion were bioequivalent. Pharmacokinetics:the correspond- ding distribution half-lives(t1/2α) were1.82, 2.82, 1.87min, and the elimination half-lives (t1/2β) were 33.02,31.25,53.64 min, AUC(0～t) were 60.00, 26.90, 19.61(μg/ml)·min. The concentration-time data and pharmacoki-netics parameters conformed to a 2-compartment model. The distri-bution of triptolide was rapid and wide. Tissue distribution:The propofol microemulsion injection in the tissues of the body were widely distributed, mainly in the brain and liver, followed by the distribution of the heart, kidneys, stomach and fat. At 1h after injection, the concentration of Propofol in the heart, liver, spleen and other organizations have been less than 1μg/g, the highest was fat around 0.6μg/g, showed that propofol have no significant accumulation in these organizations.