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Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions.

Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN. Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the fir

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… interaction signal. … study to assess the drug interactions between PI and FXaI on PN. …

Drug-Drug Interactions in Patients with COVID-19: A Retrospective Study at a Tertiary Care Hospital in Eastern India.

Introduction: Concomitant atrial fibrillation (AF) in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients complicates the decision-making process regarding short- and long-term antithrombotic strategies. Patient profiles and usage rates of different antithrombotic combinations in this patient subgroup in Romania are poorly described. Introduction: Coronavirus disease 2019 (COVID-19) is an emerging viral infection without any approved treatment. Investigational therapies for COVID-19 may cause clinically important drug-drug interactions (DDIs). We aimed to study drug-drug inter…

A Translational Physiologically Based Pharmacokinetics/Pharmacodynamics Framework of Target-Mediated Disposition, Target Inhibition and Drug-Drug Interactions of Bortezomib.

Bortezomib is a potent 20S proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma. Despite the extensive clinical use of bortezomib, the mechanism of the complex time-dependent pharmacokinetics of bortezomib has not been fully investigated in context of its pharmacodynamics (PD) and drug-drug interaction (DDI) profiles. Here, we aimed to develop a mechanistic physiologically based (PB) PK/PD model to project PK, blood target inhibition and DDI of bortezomib in patients. A minimal PBPK/PD model consisting of six compartments was constructed using a bottom-u

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantri…

Potential Drug-Drug Interactions with Combination Volasertib + Itraconazole: A Phase I, Fixed-sequence Study in Patients with Solid Tumors.

PURPOSE: This drug-drug interaction study determined whether the metabolism and distribution of the Polo-like kinase 1 inhibitor, volasertib, is affected by co-administration of the P-glycoprotein and cytochrome P-450 3A4 inhibitor, itraconazole. METHODS: This was an uncontrolled, open-label, fixed-sequence trial of two 21-day treatment cycles in patients with various solid tumors. In cycle 1 (test), eligible patients were administered volasertib (day 1) plus itraconazole (days -3 to 15). In cycle 2 (reference), patients received volasertib monotherapy. The primary end point was the influence

Negligible impact of highly patient-specific decision support for potassium-increasing drug-drug interactions - a cluster-randomised controlled trial.

BACKGROUND AND OBJECTIVE: Clinical decision support (CDS) might improve management of potassium-increasing drug-drug interactions (DDI). We studied CDS with five features intended to increase effectiveness: (i) focus on serious DDIs, (ii) fewer notifications, (iii) presentation of current laboratory results, (iv) timing (when adverse event becomes likelier), (v) removal of notification when appropriate. METHODS: We conducted a 1-year, hospital-wide, cluster-randomised controlled trial in the inpatient setting at a large tertiary-care academic medical centre. Three CDS types were implemented: …

Lamotrigine drug interactions in combination therapy and the influence of therapeutic drug monitoring on clinical outcomes in paediatric patients.

The aim was to study the impact of therapeutic drug monitoring (TDM) on paediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. During the period of 2001-2015, 1308 pre-dose samples were taken from 430 patients <15 years of age as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Valproic acid decreased lamotrigine clearance by 54% in bitherapy, and by 21% in triple therapy with carbamazepine. Carbamazepine increased lamotrigine clearance by 191% in bithera…

Preferences of Patients and Pharmacists with Regard to the Management of Drug-Drug Interactions: A Choice-Based Conjoint Analysis.

INTRODUCTION: The management of drug-drug interactions (DDIs) is a complex process in which risk-benefit assessments should be combined with the patient's perspective. OBJECTIVE: The aim of this study was to determine patients' and pharmacists' preferences regarding DDI management. METHODS: We conducted a choice-based conjoint survey about a fictitious DDI concerning the combination of a cardiovascular drug and an antibiotic for pneumonia. Patients and pharmacists had to choose 12 times between two management options. The options were described by five attributes, including risk, benefit and…

Contraindicated drug-drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States.

OBJECTIVES: Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. METHODS: This cross-sectional study included multiple year pooled data (2003-2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral an

Lamotrigine Drug Interactions in Combination Therapy and the Influence of Therapeutic Drug Monitoring on Clinical Outcomes of Adult Patients.

BACKGROUND: The aim was to study the impact of therapeutic drug monitoring (TDM) on patients on lamotrigine (LTG) therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. METHODS: During the period of 2001-2014, 3118 predose samples were taken from 1137 patients >15 years of age as part of their routine TDM. Drug interactions were evaluated using calculation of LTG clearance (CL). RESULTS: Valproic acid (VPA) decreased LTG CL by 66% in bitherapy, and by 35% and 31% in triple therapy with carbamazepine (CBZ) and phenytoin (PHT), respectiv…

Effect of multiple pharmacy use on medication adherence and drug-drug interactions in older adults with Medicare Part D.

OBJECTIVES: To assess the association between multiple pharmacy use and medication adherence and potential drug-drug interactions (DDIs) in older adults. DESIGN: Cross-sectional propensity score-weighted analysis. SETTING: 2009 claims data. PARTICIPANTS: A nationally representative sample of 926,956 Medicare Part D beneficiaries aged 65 and older continuously enrolled in fee-for-service Medicare and Part D that year who filled one or more prescriptions at a community retail or mail order pharmacy. MEASUREMENTS: Multiple pharmacy use was defined as concurrent (overlapping time periods) or s…

Skin and Brain in Bipolar Disorder: A Review of Dermatologic-Psychotropic Drug Interactions.

Importance: Dermatologic and psychotropic therapies intersect frequently in patients with bipolar disorder, in whom systemic dermatologic me … rativa, and severe cutaneous adverse reactions. Conclusions and Relevance: Dermatologic-psychiatric drug interactions can be clinically significant and require careful screening, counseling, and longitudinal monitoring. Dermatologists, psychiatrists, and primary care clinicians should collaborate when initiating or modifying high-risk therapies, especially when psy …

Gut Microbiota and Hypertension: Mechanisms, Drug Interactions, and Translational Directions for Individualized Therapy.

Hypertension remains a major global health challenge, with suboptimal treatment and blood pressure (BP) control rates and apparent or confirmed resistant hypertension (RHT) affecting approximately 10-20% of treated patients. Increasing evidence suggests that the gut microbiota may contribute to BP regulation through interconnected metabolic, immune-inflammatory, intestinal barrier, gut-brain, and gut-kidney pathways. Short-chain fatty acids (SCFAs) may support vasodilation, renal sodium handling, epithelial barrier integrity, and anti-inflammatory signaling through receptor- and tissue-specifi

Indole Scaffolds in Neurological Therapeutics: Synthesis, Structure- Activity Relationships and Drug-Receptor Interactions.

INTRODUCTION: Indole is a privileged heterocyclic scaffold that plays a crucial role in medicinal chemistry due to its strong ability to bind to various biological receptors and interact with diverse molecular targets. Indole exhibits both biological and chemical significance. Its structural versatility allows for precise chemical modifications, making it an essential framework in drug discovery. This review discusses the structure-activity relationships, synthesis, and interactions of indole derivatives, particularly in relation to targets within the central nervous system. METHODS: A detail

Dual-granularity feature learning reveals static and dynamic mechanisms of ncRNA-drug interactions.

Accurately identifying interactions between non-coding RNAs (ncRNAs) and drugs is crucial for elucidating drug mechanisms and advancing drug repositioning. Existing deep learning-based methods for ncRNA-drug association prediction typically leverage multi-source biological information to learn informative representations, thereby alleviating the cold-start issue arising from the scarcity of experimentally validated associations. However, the direct fusion of multi-source features often introduces feature redundancy, semantic conflicts, and high-dimensional feature sparsity, thereby hindering m

Assessment of Potential Drug Interactions in Patients With Chronic Kidney Disease Undergoing Hemodialysis.

Background: Patients with chronic kidney disease (CKD) undergoing hemodialysis commonly present multiple comorbidities and require complex medication regimens. Polypharmacy increases the risk of clinically relevant drug interactions that may compromise treatment safety and effectiveness. Objective: To estimate the prevalence of potential drug interactions among patients with CKD undergoing hemodialysis and classify these interactions according to clinical risk and mechanism of action. Methods: A cross-sectional study was conducted with patients undergoing hemodialysis at a dialysis clinic in S…

Mechanistic modeling of FcRn-dependent IgG drug interactions: Clinical applications and dosing implications.

Concomitant use of intravenous immunoglobulin (IVIG) with monoclonal antibodies (mAbs) or bispecific T-cell engagers (TCEs) is routinely encountered across autoimmune diseases, B-cell malignancies, immunodeficiencies, and transplantation. These therapies share a key salvage pathway through the neonatal Fc receptor (FcRn), raising the potential for pharmacokinetic (PK) and pharmacodynamic (PD) interactions. A mechanistic model of IgG disposition originally developed in mice was extended and revalidated with an array of human datasets to investigate how IVIG dose, timing, and IgG pool dynamics i

The Review on Adverse Effects of Energy Drinks and Their Potential Drug Interactions.

Background: Energy drinks (EDs) are non-alcoholic, functional beverages sold worldwide in more than 165 countries. These products are very p … literature associated with the consumption of EDs, and briefly characterize the possible ED-related drug interactions. Methods: Scientific evidence was extracted by searching the databases PubMed and Google Scholar. In addition, the reference lists of the retrieved papers were reviewed and cross-referenced to reveal additional relevant scientific evidence. Results: …

Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo.

PURPOSE: The purpose of this study was to establish an in vitro incubation system and an in vivo model to investigate the potential kinetic interactions of macitentan with imperatorin and curcumin, and to validate the potential inhibitory mechanisms using molecular docking. METHODS: In vitro, the enzyme kinetic profile of macitentan was explored in rat liver microsomes (RLM) and human liver microsomes (HLM). Furthermore, molecular docking technique was used to study the sites of action of macitentan, imperatorin, and curcumin with CYP 3A4. In vivo, the pharmacokinetic parameters of macitentan