Prediction of Transporter ‐Mediated Drug‐Drug Interactions for Baricitinib
Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, undergoes active renal tubular secretion. Baricitinib was not predicted to inhibit hepatic and renal uptake and efflux drug transporters, based on the ratio of the unbound maximum eliminating‐organ inlet concentration and the in vitro half‐maximal inhibitory concentrations (IC50). In vitro, baricitinib was a substrate for organic anion transporter (OAT)3, multidrug and toxin extrusion protein (MATE)2‐K, P‐glycoprotein (P‐gp), and breast cancer resistance protein (BCRP). Probenecid, a strong OAT3 inhibitor, increased the area under the concentration‐...
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: Maria M. Posada, Ellen A. Cannady, Christopher D. Payne, Xin Zhang, James A. Bacon, Y. Anne Pak, J. William Higgins, Nazila Shahri, Stephen D. Hall, Kathleen M. Hillgren Tags: ARTICLE Source Type: research
Leveraging a Clinical Phase Ib Proof ‐of‐Concept Study for the GPR40 Agonist MK‐8666 in Patients With Type 2 Diabetes for Model‐Informed Phase II Dose Selection
In conclusion, MK‐8666 was generally well tolerated with robust glucose‐lowering efficacy. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - July 1, 2017 Category: Biomedical Science Authors: AW Krug, P Vaddady, RA Railkar, BJ Musser, J Cote, AGH Ederveen, DG Krefetz, E DeNoia, AL Free, L Morrow, MV Chakravarthy, E Kauh, DA Tatosian, PA Kothare Tags: ARTICLE Source Type: research
G ‐CSF Indirectly Induces Apoptosis of Osteoblasts During Hematopoietic Stem Cell Mobilization
The objective of this study was to explore the mechanism underlying osteoblast suppression in the process of hematopoietic stem cells mobilization induced by granulocyte colony‐stimulating factor (G‐CSF). The apoptosis of human and mouse osteoblasts was examined by detecting caspase 3. The levels of serum DKK1 and osteocalcin in the supernatant of co‐culture of mouse osteoblasts and mouse bone marrow nucleated cells were measured. The number of mouse osteoblasts co‐cultured with mouse bone marrow nucleated cells was measured and the osteocalcin mRNA level was also measured. The G‐CSF‐induced decrease in osteobl...
Source: Clinical and Translational Science - May 29, 2017 Category: Biomedical Science Authors: S ‐D Li, Y‐B Chen, L‐G Qiu, M‐Q Qin Tags: ARTICLE Source Type: research
Direct Oral Anticoagulants Vs. Enoxaparin for Prevention of Venous Thromboembolism Following Orthopedic Surgery: A Dose –Response Meta‐analysis
We carried out a dose–response model‐based meta‐analysis to assess venous thromboembolism (VTE) and bleeding with factor Xa (FXa) inhibitors (apixaban, edoxaban, rivaroxaban) and a thrombin inhibitor (dabigatran) compared with European (EU) (40 mg q.d.) and North American (NA) (30 mg Q12H) dose regimens of a low molecular weight heparin (enoxaparin) following orthopedic surgery. Statistically significant differences in both VTE and bleeding outcomes were found between the NA and EU doses of enoxaparin, with odds ratios (95% confidence interval) for the NA vs. EU dose of 0.73 (0.71–0.76) and 1.20 (1.14–1.29) for t...
Source: Clinical and Translational Science - May 23, 2017 Category: Biomedical Science Authors: RA Boyd, L DiCarlo, JW Mandema Tags: ARTICLE Source Type: research
Bioinformatics Analysis on Molecular Mechanism of Green tea Compound Epigallocatechin ‐3‐Gallate Against Ovarian Cancer
This article is protected by copyright. All rights reserved (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - May 15, 2017 Category: Biomedical Science Authors: Song Xinqiang, Zhang Mu, Chen Lei, Lee Yew Mun Tags: ARTICLE Source Type: research
