Shuo Yin1, Yanwen Cheng1, Tingting Li1, Mei Dong2, Haifeng Zhao1, Gaofeng Liu1. 1. a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , PR China and. 2. b Department of Pharmacy , The Third Affiliated Hospital, Harbin Medical University , Harbin , PR China.
Abstract
CONTEXT: Notoginsenoside R1 (NGR1) is the main component with cardiovascular activity in Panax notoginseng (Burk.) F. H. Chen, an herbal medicine that is widely used to enhance blood circulation and dissipate blood stasis. OBJECTIVE: The objective of this study is to investigate NGR1's effects on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats in vivo through the use of the Cytochrome P450 (CYP450) probe drugs. MATERIALS AND METHODS: After pretreatment with NGR1 or physiological saline, the rats were administered intraperitoneally with a mixture solution of cocktail probe drugs containing caffeine (10 mg/kg), tolbutamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). The bloods were then collected at a set of time-points for the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis. RESULTS: NGR1 was shown to exhibit an inhibitory effect on CYP1A2 by increased caffeine Cmax (43.13%, p < 0.01) and AUC0 - ∞ (40.57%, p < 0.01), and decreased CL/F (62.16%, p < 0.01) in the NGR1-treated group compared with those of the control group, but no significant changes in pharmacokinetic parameters of tolbutamide, metoprolol, and dapsone were observed between the two groups, indicating that NGR1 had no effects on rat CYP2C11, CYP2D1, and CYP3A1/2. DISCUSSION AND CONCLUSION: When NGR1 is co-administered with drugs that are metabolized by CYP1A2, the pertinent potential herb-drug interactions should be monitored.
CONTEXT: Notoginsenoside R1 (NGR1) is the main component with cardiovascular activity in Panax notoginseng (Burk.) F. H. Chen, an herbal medicine that is widely used to enhance blood circulation and dissipate blood stasis. OBJECTIVE: The objective of this study is to investigate NGR1's effects on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats in vivo through the use of the Cytochrome P450 (CYP450) probe drugs. MATERIALS AND METHODS: After pretreatment with NGR1 or physiological saline, the rats were administered intraperitoneally with a mixture solution of cocktail probe drugs containing caffeine (10 mg/kg), tolbutamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). The bloods were then collected at a set of time-points for the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis. RESULTS:NGR1 was shown to exhibit an inhibitory effect on CYP1A2 by increased caffeine Cmax (43.13%, p < 0.01) and AUC0 - ∞ (40.57%, p < 0.01), and decreased CL/F (62.16%, p < 0.01) in the NGR1-treated group compared with those of the control group, but no significant changes in pharmacokinetic parameters of tolbutamide, metoprolol, and dapsone were observed between the two groups, indicating that NGR1 had no effects on ratCYP2C11, CYP2D1, and CYP3A1/2. DISCUSSION AND CONCLUSION: When NGR1 is co-administered with drugs that are metabolized by CYP1A2, the pertinent potential herb-drug interactions should be monitored.