Molecular Insights into the Mechanism of Modulatory Effects of Proton Pump Inhibitors on P-glycoprotein Mediated Drug Transport of Palbociclib and Ribociclib.

Background: Palbociclib and ribociclib are substrates of efflux transporter P-glycoprotein which plays a key role in absorption and transport of these drugs. Proton pump inhibitors, when co-administered with them are known to show inhibitory effect on P-glycoprotein.

Objective: Therefore, this study aims to investigate the role of proton pump inhibitors in inhibition of P-glycoprotein mediated efflux of palbociclib and ribociclib.

Design, Synthesis of Novel, Potent, Selective, Orally Bioavailable Adenosine A Receptor Antagonists and Their Biological Evaluation.

Our initial structure-activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound 25 as a potent and selective A adenosine receptor (AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability.

Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction.

This study evaluated left ventricular diastolic function with Doppler echocardiography before and after statin therapy. Statin therapy worsened diastolic parameters in most patients; coenzyme Q(10) supplementation in patients with worsening diastolic function with statin therapy improved parameters of diastolic function.

Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical protocol.

Unlabelled: Lipid-lowering statins are thought to have a favorable safety profile. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting step of mevalonate synthesis. Mevalonate is the substrate for further synthesis of cholesterol and Co Enzyme Q10 (CoQ10).