The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug-Drug Interactions.

Background And Objectives: Numerous clinical concerns have been expressed regarding the potential worsening of cyclin-dependent kinase 4/6 inhibitor effects in breast cancer patients because of co-administration of proton pump inhibitors. Hence, this study evaluated the effects of proton pump inhibitors on the pharmacokinetics of palbociclib and ribociclib in terms of  cytochrome P450 (CYP) 3A4 and P-glycoprotein involvement.

Methods: The effects of omeprazole and rabeprazole on drug metabolism and efflux of these drugs were investigated using molecular docking, metabolic stability assay in rat liver microsomes, human recombinant CYP3A4 (rCYP3A4) enzymes, and Caco-2 cell monolayers, and in vivo pharmacokinetics with omeprazole and rabeprazole in (5 and 10 mg/kg) 30 min and 7 days before orally dosing palbociclib and ribociclib (10 mg/kg).

Estimation of CDK inhibitors by RP-HPLC: application for pharmacokinetic interactions studies with PPIs.

The study investigated pharmacokinetic interactions between palbociclib and ribociclib with proton pump inhibitors (PPIs) using the reverse-phase high-performance liquid chromatography (RP-HPLC) method. Developed RP-HPLC method quantified palbociclib and ribociclib in biological matrices. metabolic stability assays and studies in rats evaluated effect of omeprazole and esomeprazole on pharmacokinetics of palbociclib and ribociclib.

Relation between Apolipoprotein E in Alzheimer's Disease and SARS-CoV-2 and their Treatment Strategy: A Review.

COVID-19, which primarily affects the pulmonary system, turned out to be a global pandemic, whereas the effects on other systems are still unknown. SARS-CoV-2, binds to angiotensinconverting enzyme 2 (ACE2) receptors in the lungs, causing pneumonia-like symptoms. The same ACE receptors are also present in organs other than the lungs.

Should the Use of Acid Reducing Agents in Conjunction with Ribociclib be Avoided? An Integrated QbD Approach for Assessment of pH-Mediated Interaction.

The objective of the study was to evaluate the possible pH-dependent interaction of ribociclib succinate with acid-reducing agents, which are concomitantly administered as supportive care medicines in cancer. Quality by Design-based analytical method development for a weakly basic drug ribociclib succinate supposedly having the characteristic ability of pH-dependent solubility was carried out for analyzing micro-dissolution experiment samples in biorelevant media to study pH-dependent interaction. An accurate and robust analytical method was developed using a three-level three-factorial box-behnken design for quantification of ribociclib succinate in micro-dissolution samples by the implementation of the Analytical Quality by Design approach.

Inhibition of Cytochrome P450 Enzyme and Drug-Drug Interaction Potential of Acid Reducing Agents Used in Management of CDK Inhibitors for Breast Cancer Chemotherapy.

Background And Objective: Concurrent usage of proton pump inhibitors and their effect on survival and medication termination has been found in individuals receiving protein kinase inhibitor chemotherapy. To investigate the drug-drug interaction mechanism between CDK inhibitors and proton pump inhibitors, the in-silico docking approach was designed by applying computer simulation modules to predict the binding and inhibitory potential.

Methods: The interaction potential of proton pump inhibitors and CDK inhibitors was predicted utilising molecular docking techniques that employed Schrödinger algorithms to capture the dynamics of the CYP450 enzyme-inhibitor interaction between proton pump inhibitors and CDK inhibitors.

Neurodegenerative Pathways in Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a complex neurodegenerative disease that leads to insidious deterioration of brain functions and is considered the sixth leading cause of death in the world. Alzheimer's patients suffer from memory loss, cognitive deficit and behavioral changes; thus, they eventually follow a low-quality life. AD is considered as a multifactorial disorder involving different neuropathological mechanisms.