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Aims： The objective of this study was to evaluate the bioequivalence of two formulations of eldecalcitol (0.75 μg ) under fasting and fed conditions, and to explore the effect of food on the pharmacokinetic (PK) properties of eldecalcitol in healthy Chinese volunteers. Methods： A single-center, open-label, randomized, three-period, three-sequence, crossover study was performed in 27 healthy Chinese volunteers under fasting conditions. Meanwhile, a two-way crossover study was performed in 28 healthy volunteers under fed conditions. Blood samples were collected at scheduled time spots from 0 hour pre dose to 168 hours post dose following administration of 0.75 μg eldecalcitol. The PK parameters for bioequivalence evaluation calculated by non-compartment analysis include Cmax, AUC and AUC. Monitoring of adverse events throughout the study. Results： The 90% confidence intervals of the test/reference AUC ratio and C ratio were within the acceptance criteria. Under the fasting condition, T values were 3.987 h and 3.489 h in subjects after given the test and reference formulation respectively. While in the fed study, the Tmax were 9.006 h and 6.007 h respectively. Therefore, the Tmax was significantly increased (P < 0.05) under fed conditions. No severe adverse events occurred during the study and all adverse events were mild and transient. Conclusion: The generic product of eldecalcitol was bioequivalent to the reference product in terms of the rate and extent of absorption under both fasting and fed conditions. Food intake prolongs the oral absorption of eldecalcitol but does not significantly influence the system exposure.

Tranexamic Acid (TXA) is commonly administered in total knee arthroplasty for reducing blood loss. There has been a growing interest in the topical use of TXA except intravenous use for prevention of bleeding in TKA. The aim of this study was to develop and validate a HPLC-MS method to detect TXA and apply to compare the pharmacokinetic profile of TXA after intravenous (IV) and topical intra-articular (IA) application of TXA at a dose of 20 mg/kg in rabbits. In order to prove intra-articular administration is better than that of intravenous administration from the point of rabbit pharmacokinetic. Two groups of rabbits (n=6/group) respectively received TXA intra-articularly or intravenously. Blood samples were collected at scheduled time. The concentration of TXA in plasma was determined by a validated HPLC-MS method. Excellent linearity was found between 0.015 and 70.0μg/ml with a lower limit of quantitation (LLOQ) of 0.015μg/ml (r0.99); moreover, all the validation data including accuracy and precision (intra- and inter-day) were all within the required limits. The pharmacokinetic parameters in IA and IV group were: C

Numerous studies have indicated that the expression of matrix metalloproteinase-9 (MMP-9) contributes to the atherosclerotic plaque hemorrhage and rupture. Aspirin, a non-steroidal anti-inflammation drug, has been known for its anti-platelet effect in the prevention of the vascular complications of atherosclerosis. The present study aimed to investigate the pharmacological effects of aspirin on tumor necrosis factor-α (TNF-α)-induced MMP-9 expression and the underlying molecular mechanisms in murine macrophage RAW264.7 cells. Western blot analysis indicated that the protein level of MMP-9 was reduced by aspirin in a dose-dependent manner. In addition, downregulation of MMP-9 mRNA and activity were detected in aspirin-treated cells using quantitative polymerase chain reaction and a gelatin zymography assay separately. It was also observed that aspirin has a suppressive effect on the activation of nuclear factor (NF)-κB and inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases 1/2, p38 and c-Jun N-terminal kinase. Furthermore, subsequent to inhibition of the MAPK pathway by specific inhibitors (PD98059, SB203580 and SP600125), the expression of MMP-9 was reduced, indicating that the inhibitory effect of aspirin on MMP-9 in TNF-α-treated RAW264.7 cells may be, at least in part, through suppression of NF-κB activation and the MAPK pathway. These findings support the notion that aspirin has therapeutic potential application in the prevention and treatment of atherosclerosis disease.

Clopidogrel, an inhibitor of platelet ADP P2Y12 receptors, plays an important role in the prevention of stent thrombosis. However, some patients do not attain adequate antiplatelet effects. Studies have shown that the genetic variation in CYP2C19*2 is associated with an impaired response to clopidogrel. This study was designed to investigate the genetic variants of 21 genes involving in the absorption, metabolism, and pharmacodynamics of clopidogrel. The effects of these genes on the plasma level of clopidogrel and its metabolites (active clopi-H4 and inactive CLPM) and platelet reactivity were also studied.401 acute coronary syndrome (ACS) patients received either a 300 mg loading dose following 75 mg maintenance dose daily or a 75mg maintenance dose daily of clopidogrel. The inhibition of platelets was assessed using light transmittance aggregometry. Plasma concentrations of clopidogrel as well as its active (clopi-H4) and inactive (CLPM) metabolites were measured using HPLC-MS-MS method. Among 21 genes, the carriers of CYP2C19*2 were associated with lower exposure to its active (clopi-H4) and inactive (CLPM) metabolites (both P0.05 vs. non-carriers) and thus decreased platelet inhibition (P0.05 vs. non-carriers). Notably, the carriers of ABCB1 C3435T were associated with lower levels of plasma clopidogrel and its active (clopi-H4) and inactive (CLPM) metabolites (all P0.05 vs. non-carriers) which also correlated with subsequently decreased platelet inhibition (P0.05 vs. non-carriers). There were no obvious effects of other studied genes on clopidogrel.CYP2C19*2 is a determinant for the formation of the active metabolite of clopidogrel and its antiplatelet effects. Meanwhile, ABCB1 C3435T plays an important role in intestinal absorption of clopidogrel which further affects the exposure to the active metabolite of clopidogrel and platelet aggregation.