Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent.

Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent.

PLoS One. 2013; 8(5): e64114
Lee JW, Kang HJ, Choi JY, Kim NH, Jang MK, Yeo CW, Lee SS, Kim H, Park JD, Park KD, Shin HY, Shin JG, Ahn HS

Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing -1774 del and/or -24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR?=?7.17, 95% CI?=?1.79-28.67, P?=?0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ?40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR?=?8.48, 95% CI?=?1.7-43.57, P?=?0.010 and OR?=?14.17, 95% CI?=?1.34-150.35, P?=?0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox. HubMed – drug


Predictors of diffuse-type in-stent restenosis following drug-eluting stent implantation.

Exp Ther Med. 2013 May; 5(5): 1486-1490
Park CB, Park HK

Diffuse-type in-stent restenosis (ISR) is known to be associated with a higher rate of restenosis than focal-type ISR. Therefore, it is clinically important to identify the determinants of diffuse-type ISR following drug-eluting stent (DES) implantation. We investigated the clinical, procedural and angiographic variables for predicting diffuse-type ISR following DES implantation. A total of 173 ISR lesions in 159 patients (diffuse-type: 61 lesions, focal-type: 112 lesions) following DES implantation from February 2003 to May 2008 were included in this study. Clinical, procedural and quantitative coronary angiographic variables were analyzed to determine predictors of diffuse-type ISR following DES implantation. Univariate analysis showed that the absence of hypertension [odds ratio (OR), 0.493; 95% confidence interval (CI), 1.025-4.103, P=0.042], use of a paclitaxel-eluting stent (PES) (OR, 3.318; 95% CI, 1.730-6.365, P<0.001) and smaller post-stenting minimal luminal diameter (MLD; OR, 0.368, 95% CI, 0.168-0.808, P=0.013) were significantly associated with diffuse-type ISR. However, use of a PES (OR, 3.957; 95% CI, 1.977-7.922, P<0.001) and smaller post-stenting MLD (OR, 0.320; CI, 0.140-0.731, P=0.007) were only independent predictors of diffuse-type ISR by multivariate analysis. Diabetes was not a predictor of diffuse-type ISR. The use of a PES and the post-stenting MLD were related to diffuse-type ISR following DES implantation. HubMed – drug


A network pharmacology approach to evaluating the efficacy of chinese medicine using genome-wide transcriptional expression data.

Evid Based Complement Alternat Med. 2013; 2013: 915343
Wu L, Wang Y, Nie J, Fan X, Cheng Y

The research of multicomponent drugs, such as in Chinese Medicine, on both mechanism dissection and drug discovery is challenging, especially the approaches to systematically evaluating the efficacy at a molecular level. Here, we presented a network pharmacology-based approach to evaluating the efficacy of multicomponent drugs by genome-wide transcriptional expression data and applied it to Shenmai injection (SHENMAI), a widely used Chinese Medicine composed of red ginseng (RG) and Radix Ophiopogonis (RO) in clinically treating myocardial ischemia (MI) diseases. The disease network, MI network in this case, was constructed by combining the protein-protein interactions (PPI) involved in the MI enriched pathways. The therapeutic efficacy of SHENMAI, RG, and RO was therefore evaluated by a network parameter, namely, network recovery index (NRI), which quantitatively evaluates the overall recovery rate in MI network. The NRI of SHENMAI, RG, and RO were 0.876, 0.494, and 0.269 respectively, which indicated SHENMAI exerts protective effects and the synergistic effect of RG and RO on treating myocardial ischemia disease. The successful application of SHENMAI implied that the proposed network pharmacology-based approach could help researchers to better evaluate a multicomponent drug on a systematic and molecular level. HubMed – drug