ABSTRACT
Pachymic acid is a wildly used traditional Chinese medicine with various pharmacological features. It also exists in many drugs which are wildly used in pediatric.The effect of pachymic acid on the activity of eight major CYP isoforms was investigated in human liver microsomes.The effects of pachymic acid on eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs), and the enzyme kinetic parameters were calculated.The activity of CP3A4, 2E1, and 2C9 was inhibited by pachymic acid in a concentration-dependent manner with IC50 values of 15.04, 27.95, and 24.22 µM, respectively. Pachymic acid is a non-competitive inhibitor of CYP3A4, with the Ki value of 6.47 µM. While the inhibition of CYP2E1 and 2C9 was performed in a competitive manner, with the Ki value of 11.96 and 10.94 µM, respectively. Moreover, the inhibition of CYP3A4 was in a time-dependent manner with the KI/Kinact value of 7.77/0.048 min-1 µM-1.The in vitro inhibitory effect of pachymic acid on the activity of CYP3A4, 2E1, and 2C9 indicated the potential drug-drug interaction with the drugs that metabolized by CYP3A4, 2E1, and 2C9. Further clinical and in vivo studies are needed to evaluate the significance of this interaction.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Drugs, Chinese Herbal/pharmacology , Triterpenes/pharmacology , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP3A/metabolism , Drug Interactions , Humans , Microsomes, Liver/metabolismABSTRACT
BACKGROUND: Myocardial infarction (MI) is rare in children, and Kawasaki disease is now recognized as the main cause for MI. In this report, we present a child with MI caused by myocardial bridge (MB). METHODS: A 7.5-year-old boy was admitted to Weifang People's Hospital on September 16, 2008 for heart disease. By electrocardiogram, coronary CT angiography, emission computed tomography, and other examinations, he was initially diagnosed as having (1) acute inferior myocardial infarction and extensive anterior myocardial infarction; (2) fulminant myocarditis; or (3) coronary myocardial bridge. He was treated with oxygen, thrombolysis, myocardial nutrition, vitamin C (4.0 g per time), dexamethasone (7.5 mg per time), a large dose of gamma globulin, and interferon. RESULTS: Myocardial enzymes, liver function, C-reactive protein, and troponin-I returned to normal at 21 days after treatment. At 29 days, electrocardiogram indicated that II, III, aVF, V4 - V6 leads had abnormal Q wave, and ST-T changed. The patient was discharged. CONCLUSION: Myocardial bridge may be one of the causes of MI in children.
