Rhabdomyolysis risk from the use of two‐drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis

Q3 · MEDICINE

Article

Author: Gosho, Masahiko

AbstractRhabdomyolysis is one of the most concerning complications of antidyslipidemic drugs. Most patients with dyslipidemia take multiple medications. Our objective was to explore which two‐drug combinations lead to a higher risk of rhabdomyolysis. We analyzed data from the Japanese Adverse Drug Event Report (JADER) database between April 2004 and September 2017. The primary outcome was the report of rhabdomyolysis. We assessed the risk of rhabdomyolysis for the two‐drug concomitant use of antidyslipidemic drugs (statin, fibrate, and ezetimibe) with antihypertensive and antidiabetic medications. The Norén and Gosho methods were used for detecting two‐drug interactions. The JADER contained 468 292 records for patient characteristics, 2 973 172 drug information records, and 741 016 adverse reactions records. Rhabdomyolysis was reported in 5 017 patients. Concomitant use of pravastatin/fenofibrate, simvastatin/mefruside, fluvastatin/temocapril, bezafibrate/temocapril, bezafibrate/spironolactone, bezafibrate/metoprolol, bezafibrate/losartan, fluvastatin/mitiglinide, or fenofibrate/glibenclamide was detected as the signal of rhabdomyolysis in this analysis. Combination therapy with the drugs listed above has the potential of drug–drug interactions that could result in rhabdomyolysis in patients with dyslipidemia.

01 Jul 2014·SLAS Discovery

SEC-TID: A Label-Free Method for Small-Molecule Target Identification

Article

Author: Bauer, Andras J ; Jahnke, Wolfgang ; Michaud, Gregory A ; Tutter, Antonin ; Tallarico, John ; Raphael, Jacob ; Li, Shu ; Bourgier, Emmanuelle ; Salcius, Michael ; Rondeau, Jean-Michel ; Hao, Qin

Bioactive small molecules are an invaluable source of therapeutics and chemical probes for exploring biological pathways. Yet, significant hurdles in drug discovery often come from lacking a comprehensive view of the target(s) for both early tool molecules and even late-stage drugs. To address this challenge, a method is provided that allows for assessing the interactions of small molecules with thousands of targets without any need to modify the small molecule of interest or attach any component to a surface. We describe size-exclusion chromatography for target identification (SEC-TID), a method for accurately and reproducibly detecting ligand-macromolecular interactions for small molecules targeting nucleic acid and several protein classes. We report the use of SEC-TID, with a library consisting of approximately 1000 purified proteins derived from the protein databank (PDB), to identify the efficacy targets tankyrase 1 and 2 for the Wnt inhibitor XAV939. In addition, we report novel interactions for the tumor-vascular disrupting agent vadimezan/ASA404 (interacting with farnesyl pyrophosphate synthase) and the diuretic mefruside (interacting with carbonic anhydrase XIII). We believe this method can dramatically enhance our understanding of the mechanism of action and potential liabilities for small molecules in drug discovery pipelines through comprehensive profiling of candidate druggable targets.

01 Feb 2012·Journal of Mass SpectrometryQ4 · CHEMISTRY

On the inter‐instrument and the inter‐laboratory transferability of a tandem mass spectral reference library. 3. Focus on ion trap and upfront CID

Q4 · CHEMISTRY

Article

Author: Josephs, Jonathan L. ; Pitterl, Florian ; Siapi, Eleni ; Grosse, Sylvia ; Chacko, Silvi A. ; Letzel, Thomas ; Poschner, Bernhard ; Oberacher, Herbert ; Steele, Barry R. ; Tagliaro, Franco ; Gottardo, Rossella

Mass spectral libraries represent versatile tools for the identification of small bioorganic molecules. Libraries based on electron impact spectra are rated robust and transferable. Tandem mass spectral libraries are often considered to work properly only on the instrument that has been used to build the library. An exception from that rule is the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’. In various studies with data sets from different kinds of tandem mass spectrometric instruments, the outstanding sensitivity and robustness of this tandem mass spectral library search approach was demonstrated. The instrumental platforms tested, however, mainly included various tandem‐in‐space instruments. Herein, the results of a multicenter study with a focus on upfront and tandem‐in‐time fragmentation are presented. Five laboratories participated and provided fragment ion mass spectra from the following types of mass spectrometers: time‐of‐flight (TOF), quadrupole–hexapole–TOF, linear ion trap (LIT), 3‐D ion trap and LIT–Orbitrap. A total number of 1231 fragment ion mass spectra were collected from 20 test compounds (amiloride, buphenin, cinchocaine, cyclizine, desipramine, dihydroergotamine, dyxirazine, dosulepin, ergotamine, ethambutol, etofylline, mefruside, metoclopramide, phenazone, phentermine, phenytoin, sulfamethoxazole, sulfamoxole, sulthiame and tetracycline) on seven electrospray ionization instruments using 18 different instrumental configurations for fragmentation. For 1222 spectra (99.3%), the correct compound was retrieved as the best matching compound. Classified matches (matches with ‘relative average match probability’ >40.0) were obtained for 1207 spectra (98.1%). This high percentage of correct identifications clearly supports the hypothesis that the tandem mass spectral library approach tested is a robust and universal identification tool. Copyright © 2012 John Wiley & Sons, Ltd.

100 Deals associated with Mefruside

External Link

KEGG	Wiki	ATC	Drug Bank
D01877	Mefruside	C03BA05	DB13405

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Essential Hypertension	JP	Mitsubishi Tanabe Pharma Corp.	27 Nov 1976
Hypertension, Renal	JP	Mitsubishi Tanabe Pharma Corp.	27 Nov 1976
Edema	JP	Mitsubishi Tanabe Pharma Corp.	20 Jan 1975

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis