Effects of dipfluzine hydrochloride on cytochrome P450 enzymes in rats / 中国药学杂志

OBJECTIVE: To evaluate the effects of dipfluzine hydrochloride (Dip) on CYP450s activities in vitro and in vivo in rats. METHODS: Markers were incubated in the normal rat liver microsomes with Dip (0-200 μmol·L-1) and the concentration of metabolites of the markers were determined by LC-MS/MS, and then the ratios were calculated to evaluate the effects of Dip on the CYP450s activities. Dip was administered by orally to the male SD rats at doses of 30, 60 and 90 mg·kg-1 body weight and phenobarbital was administered at doses of 120 mg·kg-1 body weight for 14 d. At the fifteenth day, the rats were orally administered the Cocktail probe markers and blood samples were collected via medial angle of eye at different time. The concentrations of markers were determined by LC-MS/MS and the drug-time curve was plotted, by which the pharmacokinetic parameters were calculated. And then the rat liver microsomes were prepared and the probe markers were added into the incubation samples. The concentrations of the probe markers and its metabolites were determined and the metabolism ratios were calculated. The effects of Dip on CYP450s activities were evaluated by comparing the following outcomes between the experimental groups and the control group: the relative liver weight, the concentrations of protein, the contents of CYP450 enzymes, the drug concentration-time curves, the pharmacokinetic parameters and the metabolism ratios of the probes. RESULTS: In the normal rat liver microsomes, Dip had the inhibitive effects on CYP2D1, CYP2C6 and CYP2C11, and the IC50 were 8.85, 20.93 and 69.45 μg·mL-1, respectively. Dip had no effect on the relative weight of livers, the protein concentrations and the CYP450 content for the rats after they were fed on Dip for 14 d, but these indexes were raised remarkably when phenobarbital was administered by orally to rats. The results displayed that the low-dose Dip inhibited the activity of CYP2D1 or induced the activity of CYP2C11 in rats. Moderate-dose Dip showed the abilities to inhibit CYP2D1, but induce CYP2C11 and CYP3A. High-dose Dip had the certain inhibitive effects to CYP2C6 and CYP2D1, and had the inductive effects on CYP2C11 and CYP3A. CYP1A2, CYP2C11, CYP2C12, CYP2D1 and CYP3A were all induced after administration of phenobarbital. CONCLU SION: The results of liver microsomes incubation and blood plasma from the normal and Dip-induced rats all show that Dip inhibit the activities of CYP2C6 and CYP2D1, however, Dip inhibit CYP2C11 in vitro and induce it in vivo.

Omeprazole affects clopidogrel efficacy but not ischemic events in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Omeprazole, usually used in the antiplatelet therapy during percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS), has been reported to increase ischemic events in retrospective studies. However, other clinical trials gave paradoxical results. The aim of this study was to assess the effects of omeprazole on clopidogrel efficacy and clinical events.</p><p><b>METHODS</b>All patients (n = 172) received aspirin (loading dose 300 mg and maintenance dose 100 mg/d) and clopidogrel (loading dose 600 mg and maintenance dose 75 mg/d) during the therapy. They were randomized to receive omeprazole (20 mg/d) or placebo for 30 days. Residual platelet activities in the adenosine 5'-diphosphate (ADP) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping. The clinical events were recorded after one month.</p><p><b>RESULTS</b>According to the five levels of platelet activities, the frequency distributions of the inhibition rates were significantly different (P = 0.0062). However, no significant change was seen in the distribution among the highest or the lowest inhibiting levels (> 95% and < 30% inhibition rate). And there were no significant differences (P > 0.05) in events incidence, while gastro-intestinal bleeding decreased in co-administration of omeprazole.</p><p><b>CONCLUSIONS</b>Omeprazole significantly blunts clopidogrel efficacy while not exacerbates ischemic events in ACS undergoing PCI. Omeprazole even can decrease gastro-intestinal bleeding in those patients.</p>

Effects of aqueous extract in herba of Lysimachia christinae on hyperuricemia in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study hypouricemic effect of aqueous extract of Lysimachia christinae on hyperuricemia in mice.</p><p><b>METHOD</b>The uricase inhibitor potassium oxonate was used to induce hyperuricemia in mice, and serum uric acid level was determined with the phosphotungstic acid method.</p><p><b>RESULT</b>The aqueous extract of Lysimachia christinae, when administered orally to the oxonate-induced hyperuricemic mice at the doses of 5.2, 10.4 and 20.8 g.kg-1, was able to elicit dose-dependent hypouricemic effects. At these doses of the extract, the serum urate levels of the oxonate-pretreated mice showed no difference from the normal mice. In normal mice, however, oral administration of the extract at the same doses did not produce any observable hypouricemic effects.</p><p><b>CONCLUSION</b>The aqueous extract of Lysimachia christinae possesses potent hypuricemic effects on models of hyperuricemia in mice pretreated with oxonate.</p>