Urine 6¦Â-hydroxy Cortisol / Hydrocortisone Ratio To Assess Cyp3a Activity And Guidance For Children Of Personalized Medicine

Liver plays an important role in drug metabolism,and various enzyme systems are responsible for biotransformation in liver.The CYP3A enzymes are the most important and abundantly expressed cytochrome P450 enzymes in liver,and also expressed in intestine, stomach,esophagus and peripheral blood.Furthermore,CYP3A are very important for oxidative biotransformation of endogenous compounds and exogenous chemicals.However, CYP3A enzymes can be influenced by many factors,such as genetic polymorphism, hormone,age,medicine,disease,alcohol and so on.The medicine is the most impotant factor and can conspicuously change the activity of CYP3A enzymes above them.In order to help patients obtaining best therapeutic efficacy,and also refraining from drug adverse reactions, CYP3A enzymatic activity in clinic needs to be measured for the real individual therapy.So far,the common assay methods of CYP3A enzymatic activity include erythromycin breath test,midazolam and so on,but all of them need to take epactal chemicals as probe. Recently,some researchers find that urinary metabolite of endogenous cortisol may estimate CYP3A enzymatic activity.Without probe and non-invasive,urinary metabolite of exogenous cortisol may be the safest and most simple way to estimate CYP3A activity.At the same time, this simple and non-invasive procedure can retrieve medicine concentration measurement insufficient,and also provide a new way for individual therapy.In the study,we plan to screen the CYP3A activity in Chinese healthy children by measuring 6β-hydroxycortisol in urinary excretion through high-performance liquid chromatographic method.Moreover,we will use this new method to study acute lymphoblastic leukemia children,which may help us to gain some new suggestion and theory foundation for individual therapy.There are four parts in the study:The first part:To evaluate the accuratissime and feasibility of stimated cytochrome P450 activity by determining 6β-OHFC/FC in urinary through HPLC method.The second part:By using measure 6β-OHFC/FC in urinary,we study distribute of CYP3A activity in Chinese healthy children,and also analyze all the influnced factors such as age,gender,juvenescent phase and so on.The third part:We enrolled 55 acute leukocythemia children in the study,and then study 6β-OHFC/FC.We contrast the 6β-OHFC/FC proportionalities of AP∶PA chems and different disease to look forward to investigate the possible influencing factors.In the study, we find that chemical will significant chang CYP3A activity.Moreover,there is significant relationship between CYP3A activity and curative effect.This result suggests that maybe it is same relationship beween CYP3A activity and substrate pharmacodynamics.The fourth part:We used VP16 to study the relationship between pharmacokinetics parameter and CYP3A activity.In our study,we found no relationship between VP16 plasma concentration and CYP3A activity,but significant relationship between half life and CYP3A activity is found.This result suggests that CYP3A activity can influence the metabolite and excrete of VP16.So,this phenomenon suggests that the adjustment of administration frequency in clinical can influence the plateau concentration of VP 16.