RESUMO
The traditional approaches of pharmacokinetics (PK) focused on the dynamic changing process of single or several effective components of drugs in vivo,which was noted as limitations for the complexity studies on PK of multicomponent herbal medicine featuring multi-component,multi-target and multi-effect.It was turned into a bottleneck in the modernization process of traditional Chinese medicine,which could have made misunderstanding of pharmacological and toxicological knowledge of Chinese herbal medicine and its combination drugs.Owing to the advanced high-throughput platforms and various big data mining technology,metabolomics was capable for simultaneously detecting and depicting the variations of hundreds or even thousands of small molecules offering new opportunities for the PK studies on some complicated components.This review summarized recent PK studies over multicomponent drugs and chiefly introduced two remarkable applications to metabolomics in pharmacokinetics research,Chinmedomics and Poly-PK,integrating the theories of both metabolomics and traditional PK.The challenges and strengths of the two new strategies were also expounded.
RESUMO
<p><b>BACKGROUND</b>Percutaneous coronary intervention (PCI) could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property. The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.</p><p><b>METHODS</b>From March 2012 to May 2014, one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital, were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes, 24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase-myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at baseline and then 24 hours following PCI.</p><p><b>RESULTS</b>Plasma CRP and IL-6 levels increased from baseline after PCI in all groups. CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group ((9.14±3.02) mg/L) than in the LD group ((11.06±3.06) mg/L) and ND group ((12.36±3.08) mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group ((16.19±5.39) ng/L and (14.26±4.12) ng/L, respectively)) than in the LD group ((19.26±6.34) ng/L and (16.03±4.08) ng/L, respectively, both P < 0.05) and ND group ((22.24±6.98) ng/L and (17.24±4.84) ng/L, respectively). IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours after the procedure in all groups, the elevated CK-MB and cTnI values were lower in the HD group ((4.71±4.34) ng/ml and (0.086±0.081) ng/ml, respectively) than in the ND group ((7.24±6.03) ng/ml and (0.138±0.103) ng/ml, respectively, both P < 0.01) and LD group ((6.80±5.53) ng/ml and (0.126±0.101) ng/ml, respectively, both P < 0.01).</p><p><b>CONCLUSION</b>Short-term high-dose atorvastatin treatment before PCI significantly reduced systemic inflammatory response and myocardial ischemic injury elicited by PCI.</p>