Understanding Of Drug-drug Interactions Research Articles

Drug-Drug Interaction Knowledge among Healthcare Professionals

Background: The healthcare professionals who are closest to patients receiving medication include medical doctors, nurse practitioners, and pharmacists. To develop new strategies to lower drug drug interactions (DDIs), it is crucial to comprehend the extent to which these providers can recognize an interaction and identify a suitable management strategy. The scant information that is currently available suggests that there is little DDIs understanding of medical doctors, nurse practitioners, and pharmacists. Aim of the study: It's critical to evaluate healthcare providers' understanding of drug-drug interactions and common sources of information on these interactions in order to increase patient medication safety. Method: A cross-sectional study design will be applied. More than twenty drug combinations will be given to participants, and they must categorize them as "no interaction," "may be used together with monitoring," "contraindication," or "not sure." The study will be carried out in the King Hussein Medical Center at the Royal Medical Services for two months after obtaining the ethical approval. The target population will be all physicians, nurses, and pharmacists working at KHMC whereas the sample will be all physicians, nurses, and pharmacists who agree to participate in the study and provide a consent form. Utilizing SPSS for Windows version 24 statistical software, data will be analyzed. Means will be used to describe continuous variables in descriptive analysis, whereas frequency distributions (such as percentages) will be used to describe categorical variables. For categorical variables, Fisher's exact test will be applied, and for continuous variables, Student's t-test will be employed. To describe the results of possible drug/drug interaction questions, the mean will be computed. Results: The study was done by enrolling 350 healthcare professionals among whom 60 were Physician, 40 Pharmacist, 200 Nurses and 50 allied healthcare providers. ..........

Assessment of community pharmacists' knowledge about drug-drug interactions in Jeddah, Saudi Arabia.

Background: Drug-drug interactions (DDIs) have the potential to result in severe adverse drug events and profoundly affect patient outcomes. The pivotal role community pharmacists assume in recognizing and effectively managing these interactions necessitates a comprehensive understanding and heightened awareness of their implications. Such knowledge and awareness among community pharmacists are fundamental for ensuring the delivery of safe and efficacious care to patients. Aim: This study aimed to assess the knowledge of community pharmacists in Jeddah, Saudi Arabia, regarding drug-drug interactions (DDIs). Method: A cross-sectional survey was administered to a cohort of 147 community pharmacists through the utilization of a self-administered questionnaire. The questionnaire encompassed a comprehensive range of 30 multiple-choice questions, encompassing various facets pertaining to drug-drug interactions (DDIs). Results: A total of 147 community pharmacists working in Jeddah City, Saudi Arabia, completed the survey. The majority of them were male (89.1%, n = 131), and had bachelor's degrees in pharmacy. Results showed that the lowest correct response of DDIs was between Theophylline/Omeprazole, while the highest was between amoxicillin and acetaminophen. Results revealed that among the 28 drug pairs, only six pairs were determined correctly by most participants. The study found that majority of the studied community pharmacist could not determine the correct answer on drug-drug interaction knowledge, as also seen with the measured below half mean DDIs knowledge of 38.22 ± 22.0 (min = 0, max = 89.29, median = 35.71). Conclusion: The study highlights the need for ongoing training and education programs for community pharmacists in Saudi Arabia to enhance their knowledge and understanding of DDIs, ultimately leading to improved patient care and safety.

Misunderstanding of dosing regimen instructions among patients with chronic diseases receiving polypharmacy at the University of Gondar comprehensive specialized hospital.

Misunderstanding dosage instructions in terms of dose, frequency, duration, or any other instruction with patients on polypharmacy is a common problem that leads to the irrational use of medications. This study aimed to assess the level of misunderstanding of dosing instructions among patients with chronic diseases receiving polypharmacy at the chronic outpatient pharmacy of the University of Gondar Compressive Specialized Hospital (UoGCSH). An institutional-based cross-sectional survey was conducted from September to November 2021 at the UoGCSH chronic outpatient pharmacy in Northwest Ethiopia. Study subjects were selected by a systematic random sampling method. Drug-drug and drug-food interactions were also checked by Medscape and drug.com to evaluate the significance of interactions. Frequency, percentage, and mean standard deviation (SD) were used to describe the distributions of variables. With a statistical significance level of p < 0.05, the Chi-square test was used to assess the association of variables with the primary outcome. From a total of 400 participants, more than half (59%) were females, with a mean (SD) age of 57 (±16.3) years old. The study revealed that almost half (50.8%) of the participants misunderstood at least one dosage instruction, and around two-fifths (38.5%) misunderstood the frequency of drug administration. More than 90% of patients had no understanding of drug-drug interactions (DDIs). Sex (X2 = 16.837; P<0.0001), educational level (X2 = 50.251; P < 0.0001), residence (X2 = 5.164; P < 0.023) and duration of stay on medication (X2 = 13.806; P < 0.0003) were significantly associated with misunderstanding of dosage regimen instructions. The study showed that a significant number of patients did not understand their medication dosage regimen instructions. To address these significant drug-related issues, healthcare providers could effectively engage in interventions such as written instructions accompanying patients and additional counseling.

Interactions of heparin derivatives with recombinant human keratinocyte growth factor: Structural stability and bioactivity effect study.

Heparin and heparan sulfate are important glycosaminoglycans that can regulate the activities of many vital proteins, especially the fibroblast growth factor (FGF) family. Because FGF7 (KGF) has an important role in tissue repair and maintaining the integrity of the mucosal barrier, recombinant human keratinocyte growth factor (rhKGF, palifermin) has been approved for the treatment of wound healing and oral cavity. Due to heparin plays an important role in the KGF signaling pathway, a more detailed study of the drug-drug interactions (DDIs) between rhKGF and heparin at the atomic level and investigating their synergistic effect on each other in terms of biology, especially in silico, is necessary for a better understanding of DDIs. In this study, DDIs between rhKGF and low-molecular weight heparin types (LMWH) were investigated. In this regard, scrutiny of the influence of the synergistic heparin types on the structure and biostability of rhKGF is accomplished using computational methods such as molecular docking and molecular dynamic simulations (MDs). Subsequently, the motion behavior of rhKGF in interaction with LMWHs was evaluated based on eigenvectors by using principal component analysis (PCA). Also, the binding free energies of rhKGF-LMWH complexes were calculated by the molecular mechanics/Poisson-Boltzmann surface area (MM-BPSA) method. The result showed that rhKGF-idraparinux (-6.9kcal/mol) and rhKGF-heparin (-6.0kcal/mol) complexes had significant binding affinity as well as they had a more stable binding to rhKGF than to other LMWH during 100 ns simulation. However, in order to confirm the curative effect of these drugs, clinical trials must be done.

Current use and future potential of (physiologically based) pharmacokinetic modelling of radiopharmaceuticals: a review.

Rationale: Physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PK) modelling approaches are widely accepted in non-radiopharmaceutical drug development and research, while there is no major role for these approaches in radiopharmaceutical development yet. In this review, a literature search was performed to specify different research purposes and questions that have previously been answered using both PBPK and population PK modelling for radiopharmaceuticals. Methods: The literature search was performed using the databases PubMed and Embase. Wide search terms included radiopharmaceutical, tracer, radioactivity, physiologically based pharmacokinetic model, PBPK, population pharmacokinetic model and nonlinear mixed-effects model. Results: Eight articles and twenty articles were included for this review based on this literature search for population PK modelling and PBPK modelling, respectively. Included population PK analyses showed to have an added value to develop predictive models for a population and to describe individual variability sources. Main purposes of PBPK models appeared related to optimizing treatment (planning), or more specifically: to find the optimal combination of peptide amount and radioactivity, to optimize treatment planning by reducing the number of measurements, to individualize treatment, to get insights in differences between pre-therapeutic and therapeutic scans or to understand inter-patient differences. Other main research subjects were regarding radiopharmaceutical comparisons, selecting ligands based on their peptide characteristics and gaining a better understanding of drug-drug interactions. Conclusions: The use of PK modelling approaches in radiopharmaceutical research remains scarce, but can be expanded to obtain a better understanding of PK and whole-body distribution of radiopharmaceuticals in general. PK modelling of radiopharmaceuticals has great potential for the nearby future and could contribute to the evolving research of radiopharmaceuticals.

S11.2 - Elagolix: A mechanistic understanding of drug-drug interactions

S11.2 - Elagolix: A mechanistic understanding of drug-drug interactions

Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions.

ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many therapeutic compounds, including anticancer drugs. The ABC transporters are also recognized as important contributors to pharmacokinetics, especially in drug-drug interactions and adverse drug effects. Drugs and xenobiotics, as well as pathologic conditions, can influence the transcription of ABC transporters, or modify their activity or intracellular localization. Kinases can affect the aforementioned processes for ABC transporters as do protein interactions. In this review, we focus on the ABC transporters ABCB1, ABCB11, ABCC1, ABCC4, and ABCG2 and illustrate how kinases and protein-protein interactions affect these transporters. The clinical relevance of these factors is currently unknown; however, these examples suggest that our understanding of drug-drug interactions will benefit from further knowledge of how kinases and protein-protein interactions affect ABC transporters.

Computerized techniques pave the way for drug-drug interaction prediction and interpretation.

Introduction: Health care industry also patients penalized by medical errors that are inevitable but highly preventable. Vast majority of medical errors are related to adverse drug reactions, while drug-drug interactions (DDIs) are the main cause of adverse drug reactions (ADRs). DDIs and ADRs have mainly been reported by haphazard case studies. Experimental in vivo and in vitro researches also reveals DDI pairs. Laboratory and experimental researches are valuable but also expensive and in some cases researchers may suffer from limitations. Methods: In the current investigation, the latest published works were studied to analyze the trend and pattern of the DDI modelling and the impacts of machine learning methods. Applications of computerized techniques were also investigated for the prediction and interpretation of DDIs. Results: Computerized data-mining in pharmaceutical sciences and related databases provide new key transformative paradigms that can revolutionize the treatment of diseases and hence medical care. Given that various aspects of drug discovery and pharmacotherapy are closely related to the clinical and molecular/biological information, the scientifically sound databases (e.g., DDIs, ADRs) can be of importance for the success of pharmacotherapy modalities. Conclusion: A better understanding of DDIs not only provides a robust means for designing more effective medicines but also grantees patient safety.

Animal Models for Evaluation of Drug-Drug Interaction Potential of Biotherapeutics

The increased development and availability of therapeutic proteins (TP) requires a greater understanding of drug-drug interactions (DDI) in a poly-pharmacy environment. Medications that are likely co-administered in various patient populations have to be considered in the context of direct pharmacokinetic properties of co-administered drugs as well as indirect effects due to disease modification. Anticipating and managing drug-drug interactions are an important part of the clinical development of both small and large molecules. Animal models may provide useful information in this regard with respect to human translatability. However, very limited work has been done to better understand the value of animal models for predicting the potential for TP DDI. Potential DDI mechanisms of TPs, with the exception of cytokine-mediated alteration of drug metabolizing enzymes and transporters, are less well known. This review discusses the potential value and specific challenges in the use of animal models for TP DDI evaluation.

Combination Drug Therapy

Caring for the elderly nursing home patient has never been more clinically complex or administratively more troublesome. Patients carry with them a greater burden of disease with increasing frailty and vulnerability. More drugs are being used for more problems. Combination drug therapy (and by this we mean 2 or more drugs in the same pill or capsule) was not common or recommended even just a few years ago. Acceptable combinations for a long time were limited and they were represented by drugs such as hydrochlorothiazide/triamterene (Dyazide; GlaxoSmithKline, Research Triangle Park, NC) and carbidopa/levodopa (Sinemet; Merck & Co, Inc, Whitehouse Station, NJ). Other fixed combinations were generally unavailable because of the significant side effect profiles of individual agents and a relatively poor understanding of drug-drug interactions. A lot has changed in a very short period of time. In an effort to extend patent protection, drug manufacturers are offering a wider array of products in combination dosage forms. Now we have available to us amlodipine/atorvastatin (Caduet; Pfizer US Pharmaceuticals, New York, NY) and ezetimibe/simvastatin (Vytorin; Merck & Co, Inc, and Schering Plough, Kenilworth, NJ) to really push the envelope on the management of cardiovascular disease, affecting blood pressure/angina and lipids at the same time. As we have come to understand the physiologic changes that come with aging (more fat, less muscle mass, and decreased albumin), today’s drugs are designed to be excreted unchanged and with mixed metabolic pathways to avoid total dependence on 1 route of elimination. Ideal pharmacokinetic characteristics of drugs in the elderly are water soluble for ease in absorption, short to intermediate half-life for once daily administration, moderate protein binding, and combined elimination by hepatic and renal routes with an emphasis on glucuronidation and sulfation, rather than oxidative metabolism. Where possible, drug manufacturers are bringing new chemical entities to market that maximize safety and efficacy. Combination drug therapy now offers physicians the opportunity to better comply with OBRA ‘87 and the 9-drug

Pharmacokinetic drug interactions with nevirapine.

Treatment of HIV infection is a multi-drug issue. Not only are there drugs for the treatment of HIV but also concomitant drugs for opportunistic infections, complications arising from the anti-retroviral therapy and other conditions related to a chronic disease. To have any understanding of drug-drug interactions in HIV treatment we need to appreciate the importance of key pharmacological areas including: 1) how each drug in a regimen is eliminated; 2) the potential for a drug to either induce or inhibit metabolic enzymes and/or transporters; 3) the therapeutic index of each drug. It is impossible to memorise all the possible drug-drug interactions in HIV, therefore understanding how drugs are metabolised/eliminated and the potential for a particular drug to modify the pharmacokinetics of another has predictive value even when substantive data are unavailable. NNRTIs interact with cytochrome P450 (CYP450) enzymes both as substrates and inducers. Because of the inductive effects caution must be exercised when using with protease inhibitors (either boosted or un-boosted with ritonavir). In this situation therapeutic drug monitoring may play a role in optimising response. There needs to be care when using many drugs with NNRTIs e.g. methadone, oral contraceptives, rifampicin, and there are some definite contraindications. By understanding pharmacological principles, it is possible to optimise use of multi-drug regimens.