| As the researches of drug metabolizing enzymes have advanced, the research of pharmacokinetics in vivo metabolism is no longer limited to identify the production and determine its purity, but the molecular enzymology and related gene molecular biology. CytochromeP450(CYP) is one of the most important represent actives of drug Metabolism enzymes,and Plays a key role in the metabolic inactivation / activation of numerous exogenous and endoxgenous. CYP exists mainly in liver microsomes. CYP superfamily shows wide range,Poor selectivity,large structure difference,inter-individual variation,over lapping substrate specificities in exogenous metabolism and can be easily induced and inhibited by a number of chemical compounds. therefore,a great Probability of competition between drugs and endogenous Compounds forth same enzyme,between different enzymes for the same substrate and between two drugs for the same enzyme. Meanwhile,many drugs are not only the substrate of the enzyme,but also the inducer or inhibitor of the enzyme or others. This may change the Pharmacological and toxicological effects of drug itself or other drugs,which is of the reasons resulting in drug interaction in Pharmacokinetics.Propofol has become the widest application as a result of the biotransformation on clinical. The classic standpoint states propofol is not oxidize metabolized by P450, it is metabolized by glucuronyltransferase in microsomes in the liver mainly from the glucose GA. A new viewpoint that all of the CYP3A4, CYP2C9, and CYP2A6...etc. P450s can metabolize propofol, among them, the 62% propofol approval glucose GA, 38% from P450 in liver. The activity of P450 is directly affected by some medicine and environment factor, even by occurrence changes of food composition. But the effect of propofol on P450 is not clear.1. Determination ED50 of propofol and phenobarbital sodium for general inductionObjective: Determination ED50 of propofol and phenobarbital sodium for general deduction. Methods: 36 rats were divided into two group randomly: pentobarbital group(group PB, n=18) and propofol group(group Pr, n=18). Drugs were injected to SD rats (body weight 180～220g) into the peritoneum and observed the behaviors of the rats, The loss of forepaw righting reflex (FRR) was considered as successful anesthesia induction, the recovery of forepaw righting reflex (FRR) was considered as regain consciousness. Determined the dosage with sequential change, the ED50 with formula of ED50=lg-1(ΣC/Σt) and the potency ratio on them was calculated. Result: The ED50 of pentobarbital and propofol were 122.415mg/kg, 59.452mg/kg respectively. The potency ratio of pentobarbital was 0.486 times that of propofol. Conclusion: This up-down method is simple, highly selective and efficient for measuring the ED50. The ED50 of pentobarbital was not reported as yet. Pentobarbital sodium and the propofol ED50 was measured with up-down method by intraperitoneal injection. The potency ratio of pentobarbital was 0.486 times that of propofol.2. The effect of propofol on the P450 in behavior.Objective: To investigate the effect of propofol on the P450 in behavior. Method: 18 male SD weighting rats was divided into three groups randomly: group phenobarbital was given 75mg/kg, group propofol was propofol 3.689mg/mg and the control was injected the same volume of normal saline for 3 days. 75mg/kg propofol was administrated at 24 hours later. The loss of forepaw righting reflex (FRR) was considered as successful anesthesia induction. Result:? To? compare? with? group? C,? incubation period is significantly shorten. Conclusion: The popofol have the same inducing properties of enzyme with phenobarbital.3.Investigate the effect of propofol on liver microsomal cytochrome P450 in rats.Objective: The purpose of this study is to investigate the effect of propofol on liver microsomal cytochrome P450 in rats. Methods: 18 male SD weighting rats were divided into three groups randomly: group phenobarbital was given 75mg/kg, group propofol was propofol 36.5mg/kg and the control was injected the same volume of normal saline for 3 days. Microsomal was prepared by Calcium precipitation. The Bradford method was used to measure the concentration of protein in liver microsomal, and activities of cytochrome P450 and aminopyrine-N-demethylase enzymes were determined by the spectrophotometer method.Result: Compared with control group, the level of microsomal protein and cytochromes P450 were increased in group PB and group PP. In PB group the activity of ANDM enzymes was much higher than group. Conclusion: propofol could induce the microsomal cytochrome P450 in rats liver, but has no effect on activity of ANDM enzymes. |
PDF Full Text Request