The Study On The Effect Of Proton Pump Inhibitors On The Activities Of Cytochrome P4501A2, N-Acetyltransferase2 And Xanthine Oxidase In Human

Objective:Cytochrome P450 enzyme 1A2 (CYP1A2), N-acetyltransferase-2 (NAT2), and xanthine oxidase (XO) play an important role while the drugs are metabolized and carcinogens are activated, their activation is closely related to curative effect or toxicity of a lot of drags and susceptibility of some tumors, different active state of three enzymes must has certain influence on transformation of chemical material in vivo. To investigate the effect of proton pump inhibitors on CYP1A2, NAT2, and XO activities in human and to forecast the drug-drag interaction of omeprazole, lansoprazole and pantoprazole, the activities of NAT2, CYP1A2 and XO are assayed by metabolic probe which are contributed to predict medicine curative effect, prevent and mitigate medicine adverse effect, improve drug safety and instruct clinician to prescribe rationally.Methods: Caffeine was used as a metabolic probe for CYP1A2, NAT2 and XO, a HPLC method of metabolites of caffeine in the urine with direct injection was established for assuring the assay accuracy. The Shim-pack VP-COD column(4.6mm×150mm ,5μm) and Shim-pack C18 pre-column were used. The mobile phase was acetonitrile and the gradient program was acetonitrile 2.5% to 8% in 0 to 24 min. The flow rate was lmL.mim"1, and the column temperature was 25°C.The detective wavelength was at 280nm. In ninety volunteers, before and after...