RESUMO
The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.
RESUMO
Cancer is one of the major harmful diseases threatening human health and life. Development of angiogenesis inhibitors targeting tumor angiogenesis has become an important topic in the field of antitumor. Vascular endothelial growth factor (VEGF), a primary factor in growth and differentiation of vascular endothelial cell, plays an important role in angiogenesis. VEGF receptors include vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. VEGF/VEGFR2 signaling pathway is a critical pathway in regulating tumor angiogenesis. The amount of new blood vessels in tumor could be reduced and the proliferation, invasion, metastasis of tumor could be inhibited by treatment targeting VEGF/VEGFR. Traditional Chinese medicine possesses characteristic in the treatment of cancer, and it has huge potential in screening and developing tumor-angiogenesis inhibitors. Progress in research of natural products targeting VEGF/VEGFR was reviewed in this paper to provide reference for further study and development of these products.
RESUMO
<p><b>BACKGROUND</b>Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.</p><p><b>METHODS</b>Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings.</p><p><b>RESULTS</b>Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120).</p><p><b>CONCLUSION</b>Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.</p>