Study On Pharmacokinetics Of Dexmedetomidine Hydrochloride In Obstructive Jaundice Rats

Objective:Hepatobiliary disease is often characterized by cholestasis, the suppression or stoppage of bile flow. The most common cause of cholestasis is extrahepatic obstruction of biliary tract(Obstructive Jaundice,OJ).Dexmedetomidine hydrochloride,a new alpha2-sdrenocepteor agonist,it is a prospective of anesthetic drugs.This experiment was to observe dexmedetomidine hydrochloride set for obstructive jaundice rat medicine dynamics and pharmacodynamics.For obstructive jaundice in the special disease group needs to consider how to appropriate adjust doses.Methods:In 16 adult male SD rats were divided into two groups: obstructive jaundice group and the control group, each group were only 8. Obstructive jaundice model: model SH operation(not only the separation of bile duct ligation) and OJ model(separation and bile duct ligation, cut off). Then the plasma was acidified with ammonium acetate solution, placed in-80°C refrigerator until determination. Venous plasma concentrations were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then to calculate the elimination half-life(t1/2) of rocuronium, the plasma-effect site equilibration rate content(Ke), the drug?s area under the curve(AUC), the mean residence time(MRT) and the other pharmacokinetic parameters use Excel.Results:1,Concentration 0.1~20.0ng/ml range, Dex and the peak area ratio of the internal standard solution concentration has a good linear relationships with Dex: y=0.003753x+0.0291(R2=0.99)2, y liquid chromatography-mass spectrometry(LC) was s-group: T1/2(min) 14.34 ± 0.91, AUC(ng ? min/m L) 40.32 ± 5.16, MRT(min) 21.67 ± 2.15, CL(m L ? kg/min) 58.46 ± 6.87 and Tmax(min) was 3.52 ± 0.74, Tlast(min) 25.61 ± 2.48, compared with s and o groups in T1/2(min) 28.63 ± 2.95, AUC(NG ? min/m L) 89.42 ± 10.23, MRT(min) 43.41 ± 4.85,CL(m L ? kg/min) 77.53 ± 8.07 and Tmax(min) 7.64 ±1.86 Tlast(min) for 35.73 ± 3.67, have increased significantly, There is a significant statistical difference between the two groups(P<0.05).Conclusions:1.The HPLC-MS/MS could be used to determine the concentration of dexmedetomidine hydrochloride in obstructive jaundice rats.2.Dex in the OJ model mice in vivo pharmacokinetics in mice characterized by a Dex of absorption, distribution, metabolism and elimination of the whole process slows down, extend drug elimination half-life, extend the average dwell time in the body, and area under the concentration-time curve of increased plasma clearance rate, extend the time to reach maximum concentrations, reaching target concentration concentration under prolonged.