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OBJECTIVE:To investigate drug combination in outpatient prescriptions of hypertension patients in our hospital, provide reference for rational drug use in clinic. METHODS:The outpatient prescriptions of patients diagnosed as hypertension dur-ing Jan. 1st to Feb. 1st in 2015 were collected from the hospital. The prescriptions of two or more than two drugs were screened, and the prescriptions of drug combination containing CYP enzyme substrate,inhibitor or inducer were recorded. Guided by metabol-ic enzymology theory,the potential metabolic drug interactions in prescriptions were evaluated on the basis of relevant literature and data reports. RESULTS:Totally 1042 prescriptions were consulted. The prescriptions of the combined medication were 551, and the potential metabolic drug-drug interactions were detected at 249 prescriptions,accounting for 45.2％. Main CYP enzyme sub-types were CYP3A4,CYP2C9,CYP2C19 and CYP2D6. Totally 214 prescriptions were correlated with CYP3A4,accounting for 85.9％ of drug interaction prescriptions;CYP3A4 substrate combined with substrate in 199 prescriptions,with inhibitor in 27 pre-scriptions,and with inducer in 11 prescriptions. Totally 27 prescriptions were correlated with CYP2C9,accounting for 10.8％ of drug interaction prescriptions;CYP2C9 substrate combined with substrate in 8 prescriptions,and with inhibitor in 20 prescriptions. Totally 27 prescriptions were correlated with CYP2D6,accounting for 10.8％ of drug interaction prescriptions;CYP2D6 substrate combined with substrate in 15 prescriptions,and with inhibitor in 12 prescriptions. Totally 4 prescriptions were correlated with CYP2C19,accounting for 1.6％ of drug interaction prescriptions;CYP2C9 substrate combined with inhibitor in 2 prescriptions, and with inducer in 2 prescriptions. CONCLUSIONS:Many metabolic drug-drug interactions are detected in the outpatient prescrip-tions of hypertension patients in our hospital. In order to improve the rationality and safety of the prescription,clinicians and phar-macists should pay attention to the drug combinations with drug-drug interactions which have been reported in the existing litera-ture,and choose similar drugs without or with little interactions.
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OBJECTIVE: To identify the specific cytochrome P450 (CYP) enzymes involved in the metabolism of dipfluzine hydrochloride (Dip) in the rat liver microsomes. METHODS: The rat liver microsomes were prepared and incubated with Dip. The Dip metabolites (M1, M2, M4 and M5) were identified by LC-MS/MS, and the CYP isoenzymes were identified by the combination of the selective CYP inhibitor study, correlation analysis and a panel of recombinant rat CYP expereiment, respectively. RESULTS: The results from the experiments of selective CYP inhibitors, correlation analysis and recombinant rat CYP isoenzymes indicated that CYP2A1, CYP3A and CYP2C11 contributed to the formation of M1 and M5 in the rat liver microsomes. CYP3A, CYP2A1, CYP1A2, CYP2C11 and CYP2E1 metabolized Dip to M2. CYP3A, CYP2A1, CYP2E1 and CYP2C11 contributed to M4 formation. And the recombinant rat CYP researches further indicated that CYP3A2 exhibited more activity than CYP3A1. CONCLUSION: CYP3A and CYP2A1 are the major CYP isoenzymes responsible for catalyzing Dip to the four metabolites formation in the rat liver microsomes.