Chronopharmacokinetics of Amlodipine in Rats / 中国药学杂志

OBJECTIVE: To study the influence of circadian dosing time on pharmacokinetics of amlodipine in rats and to assess possible pharmacokinetic interactions. METHODS: Twelve male SD rats were divided into two groups, and a single dose of amlodipine (1 mgkg-1) were given intragastrically at either 8 00 or 20 00, respectively. Plasma samples were collected at 0, 0.33, 0.67, 1, 2, 4, 8, 12 and 24 h after drug administration. A HPLC-MS-MS detection method were developed to determine amlodipine concentrations in plasma. RESULTS: Absorption of amlodipine in rat was very slowly with MRT0-t about 12 h. Dosing time schedule influnced the pharmacokinetics of amlodipine dramatically and showed higher plasma drug levels (P<0.01), larger AUC (P<0.01) and lower CL/F (P<0.01) when dosing at 20 00 compared with that at 8 00 group. The difference of drug use between ρmax, AUC0-t and MRT0-t was statistically significant (P<0.05).The ρmax is three times as large as the morning medicine, AUC is four times as large as the drug in the morning. In the evening, MRT is extended for five hours longer than in the moring. CONCLUSION: The amlodipine plasma drug concentrations are lower, and CL/F, Vd/F are larger when dosing at 8 00 than those at 20 00.The administration of amlodipine at different times of a day shows a certain effect on the pharmacokinetics of amlodipine.

Analysis of vancomycin's blood concentration monitoring and effects of renal functions in critical pa-tients / 中国药学杂志

OBJECTIVE: To study the relativity between patients' blood concentration of vancomycin and renal function, provide references for rational clinical application. METHODS: The blood concentration and renal function of 64 cases of critical patients were monitored after the usage of vancomycin, then retrospectively analyzed combined with clinical date (basic information, bacteriological results, clinical curative effect, etc.). RESULTS: Pathogenic bacteria was detected from 40 of 64 patients, accounting for 62.5%. The effective rate of vancomycin reached 81.25%. The average value of 79 monitered cases of valley concentration was (17.48± 13.22) μg ·mL-1. There was no significant difference of the level of BUN and Scr before and after the treatment of vancomycin, while the level of Ccr had the significant difference. There were significant difference of the level of BUN, Scr, Ccr between the groups of valley concentration 20 μg· mL-1. CONCLUSION: The application of vancomycin in critical patients is relatively cautions. When using the drug, the drug concentration and renal function can be adjusted according to the results of blood concentration and renal function.

Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells.</p><p><b>METHODS</b>CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells.</p><p><b>RESULTS</b>BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy.</p><p><b>CONCLUSION</b>Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.</p>

Role of Wnt Inhibitory Factor-1 in Inhibition of Bisdemethoxycurcumin Mediated Epithelial-to-Mesenchymal Transition in Highly Metastatic Lung Cancer 95D Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bisdemethoxycurcumin (BDMC) is an active component of curcumin and a chemotherapeutic agent, which has been suggested to inhibit tumor growth, invasion and metastasis in multiple cancers. But its contribution and mechanism of action in invasion and metastasis of non-small cell lung cancer (NSCLC) are not very clear. Therefore, we tried to study the effects of BDMC on regulation of epithelial-to-mesenchymal transition (EMT), which is closely linked to tumor cell invasion and metastasis.</p><p><b>METHODS</b>In this study, we first induced transforming growth factor-β1 (TGF-β1) mediated EMT in highly metastatic lung cancer 95D cells. Thereafter, we studied the effects of BDMC on invasion and migration of 95D cells. In addition, EMT markers expressions were also analyzed by western blot and immunofluorescence assays. The contribution of Wnt inhibitory factor-1 (WIF-1) in regulating BDMC effects on TGF-β1 induced EMT were further analyzed by its overexpression and small interfering RNA knockdown studies.</p><p><b>RESULTS</b>It was observed that BDMC inhibited the TGF-β1 induced EMT in 95D cells. Furthermore, it also inhibited the Wnt signaling pathway by upregulating WIF-1 protein expression. In addition, WIF-1 manipulation studies further revealed that WIF-1 is a central molecule mediating BDMC response towards TGF-β1 induced EMT by regulating cell invasion and migration.</p><p><b>CONCLUSIONS</b>Our study concluded that BDMC effects on TGF-β1 induced EMT in NSCLC are mediated through WIF-1 and elucidated a novel mechanism of EMT regulation by BDMC.</p>

Effects of combination of amlodipine and valsartan on in vivo pharmacokinetics of valsartan in rats / 中国药学杂志

OBJECTIVE: To study the phamackinetics of amlodipine and valsartan for valsartan in rats, and to investigate the antihypertensive effect of combined treatment. METHODS Twelve male SD rats were divided into two groups. The valsartan (16 mg��g-1) and Exforge(containing valsartan 16 mg��g-1, amlodipine 1 mg��g-1) were given by using stomach tube respectively to rats. Blood samples were taken for detecting plasma concentration before dosing and at 0, 0.33, 0.67, 1, 2, 4, 8, 12 and 24 h after a single intrauenous administration. A HPLC method was used to assay the valsartan concentration in plasma. RESULTS The plasma concentration-time course showed one compartment model of valsartan plasma in rats, with the increased dose after 2 h, Cmax and AUC has a significant increase(P<0.05), while Vd and CL has a significant decrease(P<0.01). CONCLUSION Combination of valsartan and amlodipine could increase the plasma concentration and AUC, while decrease CLand Vd, higher than single antihypertensive effect.