Development of method using language processing techniques for extracting information on drug-health food product interactions.

AIMS: Health food products (HFPs) are foods and products related to maintaining and promoting health. HFPs may sometimes cause unforeseen adverse health effects by interacting with drugs. Considering the importance of information on the interactions between HFPs and drugs, this study aimed to establish a workflow to extract information on Drug-HFP Interactions (DHIs) from open resources. METHODS: First, Information on drugs, enzymes, their interactions, and known DHIs was collected from multiple public databases and literature sources. Next, a network consisted of enzymes, HFP, and drugs was constructed, assuming enzymes as candidates for hubs in Drug-HFP interactions (Method 1). Furthermore, we developed methods to analyze the biomedical context of each drug and HFP to predict potential DHIs out of the DHIs obtained in Method 1 by applying BioWordVec, a widely used biomedical terminology quantifier (Method 2-1 and 2-2). RESULTS: 44,965 DHIs (30% known) were identified in Method 1, including 38 metabolic enzymes, 157 HFPs, and 1256 drugs. Method 2-1 selected 7401 DHIs (17% known) from the DHIs of Method 1, while Method 2-2 chose 2819 DHIs (30% known). Based on the different assumptions in these methods where Method 2-1 specifically selects HFPs interacting with specific enzymes and Method 2-2 specifically selects HFPs with similar function with drugs, the propsed methods resulted in extracting a wide variety of DHIs. CONCLUSIONS: By integrating the results of language processing techniques with those of the network analysis, a workflow to efficiently extract unknown and known DHIs was constructed.

Pharmacists' knowledge of drug food administration and their appropriate patient counseling a cross-sectional study from Palestine.

Pharmacists have a responsibility in the treatment of patients. Interactions between food and drugs may lead to a loss of therapeutic effectiveness or drug toxicity. Our study's objectives were to assess pharmacists' knowledge of patient counseling with regard to informing the patient about taking the drug in relation to food, as well as community pharmacists' knowledge of any pharmaceutical instructions that must be given to patients when delivering the drug. The pharmacists were assessed using an interview questionnaire. The results showed a variation in the pharmacist's knowledge about the administration of the drug with food. The chief pharmacists had better knowledge of the proper food administration counseling than that of assistant pharmacists; the percentage of those who did not give the proper food counseling was 24 vs. 58%, respectively (P < 0.05). Only (21%) of pharmacists with more work experience provided proper counseling, while only 18.2 and 18.7% of pharmacists with moderate and low work experience provided proper counseling, respectively. The study showed the pharmacists' limited knowledge of drug administration with food and outdated counseling information. It is highly recommended that a continuous education system be encouraged and enforced by the ministry of health to update pharmacist's knowledge of dispensed drugs.

Development and Validation of an Explainable Machine Learning-Based Prediction Model for Drug-Food Interactions from Chemical Structures.

Possible drug-food constituent interactions (DFIs) could change the intended efficiency of particular therapeutics in medical practice. The increasing number of multiple-drug prescriptions leads to the rise of drug-drug interactions (DDIs) and DFIs. These adverse interactions lead to other implications, e.g., the decline in medicament's effect, the withdrawals of various medications, and harmful impacts on the patients' health. However, the importance of DFIs remains underestimated, as the number of studies on these topics is constrained. Recently, scientists have applied artificial intelligence-based models to study DFIs. However, there were still some limitations in data mining, input, and detailed annotations. This study proposed a novel prediction model to address the limitations of previous studies. In detail, we extracted 70,477 food compounds from the FooDB database and 13,580 drugs from the DrugBank database. We extracted 3780 features from each drug-food compound pair. The optimal model was eXtreme Gradient Boosting (XGBoost). We also validated the performance of our model on one external test set from a previous study which contained 1922 DFIs. Finally, we applied our model to recommend whether a drug should or should not be taken with some food compounds based on their interactions. The model can provide highly accurate and clinically relevant recommendations, especially for DFIs that may cause severe adverse events and even death. Our proposed model can contribute to developing more robust predictive models to help patients, under the supervision and consultants of physicians, avoid DFI adverse effects in combining drugs and foods for therapy.

Pharmacokinetics, Bioavailability, and Swallowing Safety With Riluzole Oral Film.

Dysphagia is highly prevalent in patients with amyotrophic lateral sclerosis (ALS). Riluzole is a US Food and Drug Administration-approved treatment for ALS. Riluzole oral film (ROF; Exservan™) contains riluzole in a polymer-based film matrix. The ROF is administered by placing on the tongue, where it dissolves and the drug is ingested with the saliva. Two clinical trials assessed the safety and tolerability of the ROF. Bioavailability and pharmacokinetics (PK) were evaluated in an open-label, randomized, single-dose, replicate crossover study of 50 mg of ROF and riluzole 50-mg tablets in 32 healthy volunteers. The second study was a videofluoroscopic swallowing examination conducted with nine patients with ALS before and after receiving a single dose of 50 mg of ROF. The primary outcome was change on penetration-aspiration scale (PAS) scores from pre- to post-dose. Overall, the PK parameters for ROF and riluzole tablets were comparable between treatments and administrations when administered under fasting conditions. Administration of ROF with food resulted in a 15% reduction in area under the curve and a 45% reduction in maximum serum concentration. A total of 44 treatment-emergent adverse events (AEs) were reported in the study; all were mild in severity. No serious AEs were observed and no subjects discontinued due to AEs. In the swallowing study, very little numerical or categorical change was observed following the dose of ROF. No evidence of deterioration of swallowing function was observed post-dose. The ROF was bioequivalent to riluzole tablets, was well tolerated, and had no detrimental effect on swallowing.

Update and Application of a Deep Learning Model for the Prediction of Interactions between Drugs Used by Patients with Multiple Sclerosis.

Patients with multiple sclerosis (MS) often take multiple drugs at the same time to modify the course of disease, alleviate neurological symptoms and manage co-existing conditions. A major consequence for a patient taking different medications is a higher risk of treatment failure and side effects. This is because a drug may alter the pharmacokinetic and/or pharmacodynamic properties of another drug, which is referred to as drug-drug interaction (DDI). We aimed to predict interactions of drugs that are used by patients with MS based on a deep neural network (DNN) using structural information as input. We further aimed to identify potential drug-food interactions (DFIs), which can affect drug efficacy and patient safety as well. We used DeepDDI, a multi-label classification model of specific DDI types, to predict changes in pharmacological effects and/or the risk of adverse drug events when two or more drugs are taken together. The original model with ~34 million trainable parameters was updated using >1 million DDIs recorded in the DrugBank database. Structure data of food components were obtained from the FooDB database. The medication plans of patients with MS (n = 627) were then searched for pairwise interactions between drug and food compounds. The updated DeepDDI model achieved accuracies of 92.2% and 92.1% on the validation and testing sets, respectively. The patients with MS used 312 different small molecule drugs as prescription or over-the-counter medications. In the medication plans, we identified 3748 DDIs in DrugBank and 13,365 DDIs using DeepDDI. At least one DDI was found for most patients (n = 509 or 81.2% based on the DNN model). The predictions revealed that many patients would be at increased risk of bleeding and bradycardic complications due to a potential DDI if they were to start a disease-modifying therapy with cladribine (n = 242 or 38.6%) and fingolimod (n = 279 or 44.5%), respectively. We also obtained numerous potential interactions for Bruton's tyrosine kinase inhibitors that are in clinical development for MS, such as evobrutinib (n = 434 DDIs). Food sources most often related to DFIs were corn (n = 5456 DFIs) and cow's milk (n = 4243 DFIs). We demonstrate that deep learning techniques can exploit chemical structure similarity to accurately predict DDIs and DFIs in patients with MS. Our study specifies drug pairs that potentially interact, suggests mechanisms causing adverse drug effects, informs about whether interacting drugs can be replaced with alternative drugs to avoid critical DDIs and provides dietary recommendations for MS patients who are taking certain drugs.

Drug-food Interactions in the Era of Molecular Big Data, Machine Intelligence, and Personalized Health.

The drug-food interaction brings forth changes in the clinical effects of drugs. While favourable interactions bring positive clinical outcomes, unfavourable interactions may lead to toxicity. This article reviews the impact of food intake on drug-food interactions, the clinical effects of drugs, and the effect of drug-food in correlation with diet and precision medicine. Emerging areas in drug-food interactions are the food-genome interface (nutrigenomics) and nutrigenetics. Understanding the molecular basis of food ingredients, including genomic sequencing and pharmacological implications of food molecules, helps to reduce the impact of drug-food interactions. Various strategies are being leveraged to alleviate drug-food interactions; measures including patient engagement, digital health, approaches involving machine intelligence, and big data are a few of them. Furthermore, delineating the molecular communications across dietmicrobiome- drug-food-drug interactions in a pharmacomicrobiome framework may also play a vital role in personalized nutrition. Determining nutrient-gene interactions aids in making nutrition deeply personalized and helps mitigate unwanted drug-food interactions, chronic diseases, and adverse events from their onset. Translational bioinformatics approaches could play an essential role in the next generation of drug-food interaction research. In this landscape review, we discuss important tools, databases, and approaches along with key challenges and opportunities in drug-food interaction and its immediate impact on precision medicine.

Associated factors of potential drug-drug interactions and drug-food interactions in patients with multiple sclerosis.

Background: Multiple sclerosis (MS) is the most common immune-mediated demyelinating disease in younger adults. Patients with MS (PwMS) are vulnerable to the presence of potential drug-drug interactions (pDDIs) and potential drug-food interactions (pDFIs) as they take numerous medications to treat MS, associated symptoms and comorbidities. Knowledge about pDDIs and pDFIs can increase treatment success and reduce side effects. Objective: We aimed at determining the frequency and severity of pDDIs and pDFIs in PwMS, with regard to polypharmacy. Methods: In the cross-sectional study, we analysed pDDIs and pDFIs of 627 PwMS aged ⩾18 years. Data collection was performed through patient record reviews, clinical examinations and structured patient interviews. pDDIs and pDFIs were identified using two DDI databases: Drugs.com Interactions Checker and Stockley's Interactions Checker. Results: We identified 2587 pDDIs (counted with repetitions). Of 627 PwMS, 408 (65.1%) had ⩾ 1 pDDI. Polypharmacy (concomitant use of ⩾ 5 drugs) was found for 334 patients (53.3%). Patients with polypharmacy (Pw/P) were found to have a 15-fold higher likelihood of having ⩾ 1 severe pDDI compared with patients without polypharmacy (Pw/oP) (OR: 14.920, p < 0.001). The most frequently recorded severe pDDI was between citalopram and fingolimod. Regarding pDFIs, ibuprofen and alcohol was the most frequent severe pDFI. Conclusion: Pw/P were particularly at risk of severe pDDIs. Age and educational level were found to be factors associated with the occurrence of pDDIs, independent of the number of medications taken. Screening for pDDIs/pDFIs should be routinely done by the clinical physician to increase drug safety and reduce side effects.

Knowledge, attitudes, and practices towards drug-food interactions among patients at public hospitals in eThekwini, KwaZulu-Natal, South Africa.

Background: Drug-food interactions can lead to adverse drug reactions and therapy failure which can potentially impact patient safety and therapy outcome. Objectives: This study assessed patients' knowledge, attitudes and practices regarding drug-food interactions. Methods: A cross-sectional study was conducted among patients at three public hospitals in eThekwini, KwaZulu-Natal. Statistical analysis was performed using SPSS® version 25. The association between demographic variables and patients' knowledge, attitudes and practices were assessed. Results: Of the 342 patients, 70.5% were female, and the mean age was 42.87±0.89 years. Almost 50% of patients had secondary level education, and 64% were unemployed. About 52% of patients had high knowledge of drug-food interactions; however, only 30-50% of the patients could identify potential drug-food interactions of their drugs. More than half of the patients (51.5%) answered that they took multivitamin pills with medications and 61.7% responded they consulted healthcare professionals for drug-food interactions' information before taking new medications. Few patients (15.2%) had experienced drug-food interactions. Conclusions: Overall, patients had gaps in their knowledge and practices, and positive attitudes towards drug-food interactions. Many patients could not identify food items that can potentially interact with their drugs. It is important that education and medication counselling are provided to patients to prevent drug-food interactions, ensure optimal drug therapy and patient safety.

Pharmacokinetics and Clinical Implications of Two Non-Tablet Oral Formulations of L-Thyroxine in Patients with Hypothyroidism.

BACKGROUND: Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40-45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug-drug and drug-food interactions as well as fasting conditions that are not necessarily respected by patients. RESULTS: In this specific context, the overall information concerning those factors with the potential to affect L-T4 absorption refers only to tablet formulation. Indeed, this is the reason why new non-tablet formulations of L-T4 were introduced some years ago. In this regard, the current literature review was designed to summarize pharmacokinetic, drug and food interactions and clinical data focusing on two new oral L-T4 formulations, i.e., liquid and soft-gel capsule in healthy volunteers and patients with primary hypothyroidism. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. The impact of gastrointestinal conditions and variation of gastric pH was lower with either soft gel/solution than with tablets. In addition, the extent of drug-drug and drug-food interactions remains low and of uncertain clinical relevance. CONCLUSIONS: Pending further studies allowing one to extend the use of soft-gel/solution preparations in unselected patients, non-tablet L-T4 formulations should be considered as a first-line choice, especially in those patients with moderate-to-high potential of suboptimal tablet performance.

A comprehensive evaluation of potentially significant drug-drug, drug-herb, and drug-food interactions among cancer patients receiving anticancer drugs.

INTRODUCTION: During the cancer treatment path, cancer patients use numerous drugs, including anticancer, supportive, and other prescribed medications, along with herbs and certain products. This puts them at risk of significant drug interactions (DIs). This study describes DIs in cancer patients and their prevalence and predictors. METHODS: A cross-sectional study design was used to achieve the study objectives. The study was carried out in two centers in the northern West Bank, Palestine. The Lexicomp® Drug Interactions tool (Lexi-Comp, Hudson OH, USA) was applied to check the potential DIs. In addition, the Statistical Package for the Social Sciences (SPSS) was used to show the results and find the associations. RESULTS: The final analysis included 327 patients. Most of the participants were older than 50 years (61.2%), female (68.5%), and had a solid tumor (74.6%). The total number of potential DIs was 1753, including 1510 drug-drug interactions (DDIs), 24 drug-herb interactions, and 219 drug-food interactions. Importantly, the prevalence of DDIs was 88.1%. In multivariate analysis, the number of potential DDIs significantly decreased with the duration of treatment (p = 0.007), while it increased with the number of comorbidities (p < 0.001) and the number of drugs used (p < 0.001). CONCLUSIONS: We found a high prevalence of DIs among cancer patients. This required health care providers to develop a comprehensive protocol to monitor and evaluate DIs by improving doctor-pharmacist communication and supporting the role of clinical pharmacists.

Interacciones entre antibióticos y alimentos. Riesgo de resistencias antimicrobianas / Antibacterial agents-food interaction. Risk of antimicrobial resistance

Fundamentos: Analizar cuáles son los antibióticos y los alimentos involucrados en las interaccionesfarmacocinéticas de absorción con mayor relevancia clínica y proponer su relación con la resistencia aantibióticos.Métodos: Revisión bibliográfica narrativa basada en la búsqueda bibliográfica de estudios publicados desdeel 1996 en PubMed.Resultados: Los antibióticos más afectados han sido las tetraciclinas, las quinolonas y los antituberculosos y,de los alimentos, la leche y sus derivados. Cuando se toman conjuntamente se produce una interacciónfarmacocinética de absorción que puede comprometer la biodisponibilidad del fármaco y/o de ciertosnutrientes, como el calcio. Este tipo de interacción puede ser un factor de riesgo de las resistencias.Conclusiones: Las interacciones entre los antibióticos y los alimentos existen y pueden ser un factor de riesgode las resistencias antimicrobianas. Para evitarlas se debe separar en el tiempo la administración de estosfármacos y los alimentos. El abuso en el empleo de estos fármacos y su mala utilización durante años haoriginado una fuerte presión selectiva en el mundo microbiano, favoreciendo el incremento de laspoblaciones resistentes y, consecuentemente, más patógenas. Es imprescindible que los profesionalessanitarios tengan formación específica e información actualizada para poder detectarlas y evitarlas. (AU)

Background: Analyze which are the antibiotics and foods involved in the absorption pharmacokineticinteractions with greater clinical relevance and propose their relationship with antibiotic resistance.Methods: Narrative bibliographic review based on the bibliographic search of studies published since 1996 inPubMed.Results: The most affected antibiotics have been tetracyclines, quinolones and antituberculous drugs and,from food, milk and its derivatives. When taken together, an absorption pharmacokinetic interaction occursthat can compromise the bioavailability of the drug and / or of certain nutrients, such as calcium. This type ofinteraction can be a risk factor for resistance.Conclusions: Interactions between antibiotics and food exist and can be a risk factor for antimicrobialresistance. To avoid them, the administration of these drugs and food must be separated in time. The abusein its use and its misuse for years has caused a strong selective pressure in the microbial world, favoring theincrease of resistant populations and, consequently, more pathogenic. It is essential that health professionalshave specific training and updated information to be able to detect and avoid them. (AU)

Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration's Tainted Supplements Database 2007 Through 2021.

The US Food and Drug Administration created the Tainted Dietary Supplement Database in 2007 to identify dietary supplements adulterated with active pharmaceutical ingredients (APIs). This article compares the determination of API adulteration in dietary supplements from the 10-year time period of 2007 through 2016 to the most recent 5-year period of 2017 through 2021. From 2007 through 2021, 1068 unique products were found to be adulterated with APIs. Sexual enhancement and weight loss dietary supplements are the most common products adulterated with APIs. Phosphodiesterase-5 inhibitors are commonly included in sexual enhancement dietary supplements and a single product can include up to 5 APIs. Sibutramine, a drug removed from the market due to cardiovascular adverse events, is the most included adulterant API in weight loss products, although sibutramine analogues, phenolphthalein (which was removed from the US market because of cancer risk), and fluoxetine were also included. While muscle-building dietary supplements were commonly adulterated before 2016, since 2017 no additional adulterated products have been identified. The lack of disclosure of APIs in dietary supplements, circumventing the normal procedure with clinician oversight of prescription drug use, and the use of APIs that are banned by the Food and Drug Administration or used in combinations that were never studied are important health risks for consumers.

Recomendaciones para la administración de antineoplásicos e inmunomoduladores orales por sonda enteral en oncohematología / Recommendations for using oral antineoplastic and immunomodulating agents in oncohematology by enteral tube administration

Introducción y objetivo: en los últimos años, el número de fármacos antineoplásicos e inmunomoduladores orales (ANIOS) ha crecido enormemente. Con frecuencia, estos fármacos deben administrarse por sonda enteral (SE) o a pacientes con problemas de deglución, planteando un problema respecto a su manipulación (muchos pertenecen al grupo de medicamentos peligrosos). Además, también pueden presentar interacciones cuando se administran con la nutrición enteral (NE). El objetivo ha sido analizar y actualizar las recomendaciones de administración y manipulación de los ANIOS. Métodos: se creó un Grupo de Trabajo formado por farmacéuticos del Grupo de Farmacia de la Sociedad Española de Nutrición Clínica y Metabolismo (SENPE) y del Grupo de Nutrición Clínica de la Sociedad Española de Farmacia Hospitalaria (SEFH). Se realizó una revisión bibliográfica entre 2015 y 2020 de las condiciones de manipulación y administración de los ANIOS en oncohematología, elaborando una tabla que recoge especialidades farmacéuticas, dosis, presentación, nombre comercial, instrucciones para la administración oral y por SE, interacciones con la NE, precauciones y observaciones para su manipulación y administración. Resultados: se elaboró una tabla con 77 principios activos y 84 formas farmacéuticas, recogiendo recomendaciones e instrucciones para su administración por vía oral, sonda nasogástrica y gastrostomía, para la correcta manipulación y para la administración junto a la NE. Conclusiones: la información sobre cómo administrar y manipular los ANIOS en personas con accesos enterales o problemas de deglución es escasa. Consideramos importante incluir en los estudios poscomercialización una investigación dirigida a responder a estas cuestiones para garantizar una administración segura y eficaz de los medicamentos a estos pacientes (AU)

Introduction and objective: in recent years, the number of oral antineoplastic and immunomodulating drugs in oncohematology has increased enormously. Often, these drugs must be administered to patients with enteral tube feeding or swallowing disorders, which causes safety problems when handling these drugs (many of them are classified as hazardous drugs). In addition, it is important to note that the administration of these drugs can also interact with enteral nutrition (EN). The objective of this study was to review and update the recommendations for the administration and handling of oral antineoplastic and immunomodulating drugs. Methods: a Working Group made up of pharmacists from the Pharmacy Group of The Spanish Society of Clinical Nutrition and Metabolism (SENPE) and the Clinical Nutrition Group of The Spanish Society of Hospital Pharmacy (SEFH) was created. A bibliographic review was carried out between 2015 and 2020 on the administration and handling of oral antineoplastic and immunomodulating drugs in oncohematology. The information about pharmaceutical specialties, dosage, presentation, brand names, instructions for oral or enteral tube administration, interactions with EN, precautions, and remarks for handling and administration was analyzed. Results: a total of 77 active principles and 84 pharmaceutical forms were included. Recommendations and instructions for oral, nasogastric tube, and gastrostomy administration, handling of the antineoplastic and immunomodulating drugs, and interactions with EN were described. Conclusions: the handling and administration information about the oral antineoplastic and immunomodulating drugs currently used in oncohematology for people with enteral accesses or swallowing disorders is limited. It is important to perform post-marketing studies to ensure a safe and effective administration of these drugs (AU)

Knowledge, attitudes, and practices towards drug-food interactions among patients at public hospitals in eThekwini, KwaZulu-Natal, South Africa

Background: Drug-food interactions can lead to adverse drug reactions and therapy failure which can potentially impact patient safety and therapy outcome. Objectives: This study assessed patients' knowledge, attitudes and practices regarding drug-food interactions. Methods: A cross-sectional study was conducted among patients at three public hospitals in eThekwini, KwaZulu-Natal. Statistical analysis was performed using SPSS® version 25. The association between demographic variables and patients' knowledge, attitudes and practices were assessed. Results: Of the 342 patients, 70.5% were female, and the mean age was 42.87±0.89 years. Almost 50% of patients had secondary level education, and 64% were unemployed. About 52% of patients had high knowledge of drug-food interactions; however, only 30-50% of the patients could identify potential drug-food interactions of their drugs. More than half of the patients (51.5%) answered that they took multivitamin pills with medications and 61.7% responded they consulted healthcare professionals for drug-food interactions' information before taking new medications. Few patients (15.2%) had experienced drug-food interactions. Conclusions: Overall, patients had gaps in their knowledge and practices, and positive attitudes towards drug-food interactions. Many patients could not identify food items that can potentially interact with their drugs. It is important that education and medication counselling are provided to patients to prevent drug-food interactions, ensure optimal drug therapy and patient safety

Cardiovascular Effects of Chocolate and Wine-Narrative Review.

The consumption of food for pleasure is mainly associated with adverse health effects. This review was carried out to verify recent reports on the impact of chocolate and wine consumption on cardiovascular health, with a particular focus on atherosclerosis. On one side, these products have proven adverse effects on the cardiovascular system, but on the other hand, if consumed in optimal amounts, they have cardiovascular benefits. The submitted data suggest that the beneficial doses are 30-50 g and 130/250 mL for chocolate and wine, respectively, for women and men. The accumulated evidence indicates that the active ingredients in the products under consideration in this review are phenolic compounds, characterized by anti-inflammatory, antioxidant, and antiplatelet properties. However, there are also some reports of cardioprotective properties of other compounds such as esters, amines, biogenic amines, amino acids, fatty acids, mineral ingredients, and vitamins. Our narrative review has shown that in meta-analyses of intervention studies, consumption of chocolate and wine was positively associated with the beneficial outcomes associated with the cardiovascular system. In contrast, the assessment with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) scale did not confirm this phenomenon. In addition, mechanisms of action of bioactive compounds present in chocolate and wine depend on some factors, such as age, sex, body weight, and the presence of additional medical conditions. Patients using cardiovascular drugs simultaneously with both products should be alert to the risk of pharmacologically relevant interactions during their use. Our narrative review leads to the conclusion that there is abundant evidence to prove the beneficial impact of consuming both products on cardiovascular health, however some evidence still remains controversial. Many authors of studies included in this review postulated that well-designed, longitudinal studies should be performed to determine the effects of these products and their components on atherosclerosis and other CVD (Cardiovascular Disease) disease.

Knowledge, attitudes and practices of healthcare professionals regarding drug-food interactions: a scoping review.

OBJECTIVES: Drug-food interactions (DFIs) are a problem in clinical practice as they can alter the bioavailability of drugs and nutrients and may lead to various adverse effects. Healthcare professionals (HCPs) play a significant role in counselling patients and preventing these interactions. Knowledge, attitudes and practices (KAPs) regarding DFIs are, therefore, vital to ensure that they carry out their role efficiently. This review maps evidence on KAPs of HCPs regarding DFIs and highlights gaps for further research. METHODS: A systematic literature search for the period from 1990 to 2018 was done using Google Scholar, PubMed and ScienceDirect. Keywords such as 'knowledge, attitudes, practices, healthcare professionals, drug-food interactions' in combination with the Boolean operator (AND) were used. Articles published only in English that described KAPs of HCPs relating to DFIs were included. KEY FINDINGS: Twelve studies were included in this review. Inadequate knowledge was observed among the HCPs as they were unable to identify important DFIs. The HCPs had a positive attitude towards acquiring knowledge, reporting and counselling patients on DFIs. Most of the medical residents felt that they were inadequately trained on DFIs and over half believed that DFIs were only slightly important in clinical practice. CONCLUSION: Deficits exist in the KAPs of HCPs regarding DFIs. An educational intervention targeting HCPs is recommended. Further research assessing the KAPs of the HCPs is required as the small number of studies conducted was a limitation.

Phase 1 Study Evaluating the Effects of the Proton Pump Inhibitor Rabeprazole and Food on the Pharmacokinetics of Lorlatinib in Healthy Participants.

Lorlatinib is approved worldwide as treatment for anaplastic lymphoma kinase-positive and c-ros oncogene 1-positive non-small cell lung cancer. The objectives of this phase 1, open-label crossover study (NCT02569554) in healthy adult participants were to determine (1) the effects of the proton pump inhibitor (PPI) rabeprazole on lorlatinib pharmacokinetics (PK), (2) the effects of a high-fat meal on lorlatinib PK, and (3) the relative bioavailability of an oral solution to tablet formulation of lorlatinib under fasted conditions. Participants were followed on-study for ≥50 days after the first dose of lorlatinib. Participants received treatments over 4 periods, with a washout of ≥10 days between consecutive lorlatinib doses. Twenty-seven participants were enrolled and received lorlatinib, and all were assessed for PK and safety. Results showed no effect of multiple doses of rabeprazole on the total plasma exposure of a single oral dose of lorlatinib 100-mg tablets. The results also indicated that a high-fat meal had no effect on lorlatinib PK after a single 100-mg oral dose. In addition, the relative bioavailability of lorlatinib oral solution compared with lorlatinib tablets was complete (approximately 108%). The safety profile of lorlatinib was consistent with that reported in previous studies, and most treatment-related adverse events were mild to moderate. These data indicate that lorlatinib can be administered with drugs that modify gastric acid, including PPIs, without restriction. These results also confirm that lorlatinib can be administered regardless of food intake.

Prevalence and Clinical Significance of Drug-Drug and Drug-Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece.

BACKGROUND: Drug interactions represent a major issue in clinical settings, especially for critically ill patients such as those with cardiovascular disease (CVD) who require cardiothoracic surgery (CTS) and receive a high number of different medications. METHODS: A cross-sectional study aimed at evaluating the exposure and clinical significance of drug-drug (DDIs) and drug-dietary supplement interactions (DDSIs) in patients admitted for CTS in the University Hospital of Crete Greece. DDIs were evaluated regarding underlying pharmacological mechanisms upon admission, preoperation, postoperation, and discharge from CTS clinic. Additionally, upon admission, the use of dietary supplements (DSs) and if patients had informed their treating physician that they were using these were recorded with subsequent analysis of potential DDSIs with prescribed medications. RESULTS: The study employed 76 patients who were admitted for CTS and accepted to participate. Overall, 166 unique DDIs were identified, with 32% of them being related to pharmacokinetic (PK) processes and the rest (68%) were related to possible alterations of pharmacodynamic (PD) action. CVD medications and drugs for central nervous system disorders were the most frequently interacting medications. In total, 12% of the identified DDIs were of serious clinical significance. The frequency of PK-DDIs was higher during admission and discharge, whereas PD-DDIs were mainly recorded during pre- and postoperation periods. Regarding DS usage, 60% of patients were using DSs and perceived them as safe, and the majority had not informed their treating physician of this or sought out medical advice. Analysis of medical records showed 30 potential combinations with prescribed medications that could lead in DDSIs due to modulation of PK or PD processes, and grapefruit juice consumption was involved in 38% of them. CONCLUSIONS: An increased burden of DDIs and DDSIs was identified mostly upon admission for patients in CTS clinics in Greece. Healthcare providers, especially prescribing physicians in Greece, should always take into consideration the possibility of DDIs and the likely use of DS products by patients to promote their well-being; this should only be undertaken after receiving medical advice and an evidenced-based evaluation.

Drug interactions with Bruton's tyrosine kinase inhibitors: clinical implications and management.

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell development, differentiation and B-cell receptor (BCR) signaling. The use of Bruton's tyrosine kinase inhibitors (BTKi) in the treatment of lymphoid malignancies has dramatically increased, owing to both impressive efficacy and ease of administration. However, BTKi have a range of drug-drug and drug-food interactions, which may alter drug efficacy and/or increase toxicity. Healthcare professionals should be aware of the probability of drug interactions with BTKi and make recommendations accordingly. In this article, we discuss the relevant drug-drug and drug-food interactions associated with ibrutinib, acalabrutinib, and zanubrutinib, and provide clinical practice recommendations for managing these interactions based on the available literature.

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials.

GLPG1690 is a novel autotaxin inhibitor in development for the treatment of idiopathic pulmonary fibrosis (IPF). We report phase 1 studies investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG1690 in healthy subjects. We performed a first-in-human randomized, double-blind, placebo-controlled trial of single (20, 60, 150, 300, 600, 1000, 1500 mg) and multiple (14 days: 150 mg twice daily; 600 and 1000 mg once daily) ascending oral doses of GLPG1690 (NCT02179502), and a randomized, open-label, crossover relative bioavailability study to compare the PK of tablet and capsule formulations of GLPG1690 600 mg and to assess the effect of food on PK of the tablet formulation (NCT03143712). Forty and 13 subjects were randomized in the first-in-human and relative bioavailability studies, respectively. GLPG1690 was well tolerated, with no dose-limiting toxicity at all single and multiple doses. GLPG1690 was rapidly absorbed and eliminated, with a median tmax and mean t1/2 of approximately 2 and 5 hours, respectively. GLPG1690 exposure increased with increasing dose (mean Cmax , 0.09-19.01 µg/mL; mean AUC0-inf , 0.501-168 µg·h/mL, following single doses of GLPG1690 20-1500 mg). PD response, evidenced by rapid reduction in plasma lysophosphatidic acid (LPA) C18:2 levels, increased with increasing GLPG1690 plasma levels, plateauing at approximately 80% reduction in LPA C18:2 at around 0.6 µg/mL GLPG1690. Tablet and capsule formulations had similar PK profiles, and no clinically significant food effect was observed when comparing tablets taken in fed and fasted states. The safety, tolerability, and PK/PD profiles of GLPG1690 support continued clinical development for IPF.