Intravenous Anesthetics Hx0507 Non-clinical Pharmacokinetic Studies And Xenon Partition Coefficient In Different Concentrations Of Fat Emulsion

OBJECTIVE: Setting up the new methods to determinate the plasmaconcentrations of PRO_W, an active metabolite of HX0507 (awater-soluble prodrug of PRO), and PRO Lipid Emulsion (PRO_L) byGC-MS. To explore the pharmacokinetics of PRO_W and to compare withthe pharmacokinetics of PRO_L. METHODS: Thirty adult Beagle dogswere randomly allocated into five groups (male/female: 3/3) andgiven a single bolus of HX0507 (60, 45, 30 and 9.3 mg/kg) or a singlebolus of PRO_L (5 mg/kg). The plasma concentrations of PRO_W and PRO_Lwere determined from intravenous blood samples (0.5～1440 min), andthe pharmacokinetics of both drugs were investigated using DAS2.0.RESULT:A two-compartment model for PRO_W and a three-compartmentmodel for PRO_L best described the data. Compared with PRO_L, PRO_W fromHX0507 showed a different disposition function. The maximum plasmaconcentration (C_max) was lower for PRO_W than for PRO_L at equipotentdoses, and apparent clearance (CL) and distribution volume (Vd)were much higher for PRO_W than for PRO_L. Pharmacokinetic simulationsshowed a longer time to C_max after a bolus dose and a longer terminalelimination half-life (T_1/2) for PRO_W than for PRO_L. CONCLUSION:PRO_w from HX0507 showed a delayed onset, a sustained duration ofaction. The potency seemed to be higher with respect to plasmaconcentration but was apparently less with respect to dose. OBJECTIVE To set up a GC-MS method for determination of partitioncoefficient of Ze. To determine the partition coefficients of Xein lipid emulsion. METHODS Using HP-5MS capillary column (30m×0.32 mm×0.25μm), column temperature 40℃, the injectortemperature 120℃, split ratio 100:1, the detector MS, carryinggas high purity helium (1.5 ml/min). MS conditions the ionizationmode EI, the source temperature 230℃, the electron energy 70 eV,SIM (m/z) 129 and 132. RESULT The calibration curve of xenon hadgood linear relationship in the range of 3.1200 %～0.0122 % (r=0.998).The limit of detection is 2×10^-6. The partition coefficientsof xenon in 10 %, 20 % and 30 % lipid emulsion were determined bysyringe-syringe two-stage headspace equilibration technique.RESULT The partition coefficients of xenon in 10 %, 20 % and 30% lipid emulsion were proportional to the content of the soybeanoil in lipid emulsion. CONCLUSION As the carrier of xenon, thepossibility of using lipid emulsion to produce xenon veinpreparation was low. If xenon should he delivered by intravenousinjection, the better carrier system that has the higher xenonsolubility is cried out for.