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Current Neuropharmacology Aug 2022The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common... (Review)
Review
The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common among patients taking prescription neuropsychiatric drugs. Herb-drug interaction, a clinical consequence of this practice, may jeopardize the success of pharmacotherapy in neuropsychiatry. Besides the wellknown ability of phytochemicals to inhibit and/or induce drug-metabolizing enzymes and transport proteins, several phytoconstituents are capable of exerting pharmacological effects on the central nervous system. This study reviewed the relevant literature and identified 13 commonly used herbal products - celery, echinacea, ginkgo, ginseng, hydroxycut, kava, kratom, moringa, piperine, rhodiola, St. John's wort, terminalia/commiphora ayurvedic mixture and valerian - which have shown clinically relevant interactions with prescription drugs used in the management of neuropsychiatric disorders. The consequent pharmacokinetic and pharmacodynamic interactions with orthodox medications often result in deleterious clinical consequences. This underscores the importance of caution in herb-drug co-medication.
Topics: Ginkgo biloba; Herb-Drug Interactions; Humans; Hypericum
PubMed: 34370637
DOI: 10.2174/1570159X19666210809100357 -
Yakugaku Zasshi : Journal of the... 2018Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems... (Review)
Review
Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.
Topics: Alleles; Cytochrome P-450 CYP2D6; Drug Interactions; Flurbiprofen; Humans; Pharmaceutical Preparations; Pharmacogenetics; Polymorphism, Genetic; Pyrrolidines
PubMed: 29503430
DOI: 10.1248/yakushi.17-00191-5 -
Application of Caco-2 cell line in herb-drug interaction studies: current approaches and challenges.Journal of Pharmacy & Pharmaceutical... 2014The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes,... (Review)
Review
The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions.
Topics: Biological Availability; Caco-2 Cells; Cell Survival; Drug Evaluation, Preclinical; Herb-Drug Interactions; Humans; Intestinal Absorption
PubMed: 24735758
DOI: 10.18433/j30k63 -
Deutsches Arzteblatt International Aug 2012Drug interactions can have desired, reduced or unwanted effects. The probability of interactions increases with the number of drugs taken. The high rate of prescribed... (Review)
Review
BACKGROUND
Drug interactions can have desired, reduced or unwanted effects. The probability of interactions increases with the number of drugs taken. The high rate of prescribed drugs in elderly patients (65-year-old patients take an average of 5 drugs) increases the likelihood of drug interactions and thus the risk that drugs themselves can be the cause of hospitalization. According to meta-analyses, up to 7% of hospitalizations are drug-related.
METHODS
Selective literature review.
RESULTS
Drug interactions occur on pharmacodynamic and pharmacokinetic levels. Examples of pharmacodynamic interactions are simultaneous administration of a NSAID and phenprocoumon (additive interaction), or of aspirin and ibuprofen (antagonistic interaction). Pharmacokinetic interactions occur at the levels of absorption (e.g., levothyroxine and neutralizing antacids), elimination (e.g., digoxin and macrolides), and metabolism, as in the competition for cytochrome P450 enzymes (e.g., SSRIs and certain beta-blockers).
CONCLUSION
The systematic knowledge of drug interaction, in particular on the level of absorption, elimination, transport and drug metabolism may help to prevent adverse effects. Predicting pharmacodynamic interactions often demands a deeper understanding of the mechanisms of effect. Electronic prescribing systems are helpful.
Topics: Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Prevalence
PubMed: 23152742
DOI: 10.3238/arztebl.2012.0546 -
Expert Opinion on Drug Metabolism &... Feb 2014Non-aspirin antiplatelet agents (e.g., clopidogrel, prasugrel, ticagrelor) are commonly prescribed for the prevention of recurrent cardiovascular events among patients... (Review)
Review
INTRODUCTION
Non-aspirin antiplatelet agents (e.g., clopidogrel, prasugrel, ticagrelor) are commonly prescribed for the prevention of recurrent cardiovascular events among patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI). In addition, combination therapy with proton pump inhibitors (PPIs) is often recommended to attenuate gastrointestinal bleeding risk, particularly during dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Importantly, a pharmacological interaction between clopidogrel and some PPIs has been proposed based on mutual CYP450-dependent metabolism, but available evidence is inconsistent.
AREAS COVERED
This article provides an overview of the currently approved antiplatelet agents and PPIs, including their metabolic pathways. Additionally, the CYP450 isoenzyme at the center of the drug interaction, CYP2C19, is described in detail, and the available evidence on both the potential pharmacological interaction and influence on clinical outcomes are summarized and evaluated.
EXPERT OPINION
Although concomitant DAPT and PPI use reduces clopidogrel active metabolite levels and ex vivo-measured platelet inhibition, the influence of the drug interaction on clinical outcomes has been conflicting and largely reported from non-randomized observational studies. Despite this inconsistency, a clinically important interaction cannot be definitively excluded, particularly among patient subgroups with higher overall cardiovascular risk and potentially among CYP2C19 loss-of-function allele carriers.
Topics: Acute Coronary Syndrome; Animals; Drug Interactions; Humans; Platelet Aggregation Inhibitors; Proton Pump Inhibitors
PubMed: 24205916
DOI: 10.1517/17425255.2014.856883 -
International Journal of Molecular... Feb 2023A norm in modern medicine is to prescribe polypharmacy to treat disease. The core concern with the co-administration of drugs is that it may produce adverse drug-drug...
A norm in modern medicine is to prescribe polypharmacy to treat disease. The core concern with the co-administration of drugs is that it may produce adverse drug-drug interaction (DDI), which can cause unexpected bodily injury. Therefore, it is essential to identify potential DDI. Most existing methods in silico only judge whether two drugs interact, ignoring the importance of interaction events to study the mechanism implied in combination drugs. In this work, we propose a deep learning framework named MSEDDI that comprehensively considers multi-scale embedding representations of the drug for predicting drug-drug interaction events. In MSEDDI, we design three-channel networks to process biomedical network-based knowledge graph embedding, SMILES sequence-based notation embedding, and molecular graph-based chemical structure embedding, respectively. Finally, we fuse three heterogeneous features from channel outputs through a self-attention mechanism and feed them to the linear layer predictor. In the experimental section, we evaluate the performance of all methods on two different prediction tasks on two datasets. The results show that MSEDDI outperforms other state-of-the-art baselines. Moreover, we also reveal the stable performance of our model in a broader sample set via case studies.
Topics: Humans; Drug Interactions; Knowledge Bases; Polypharmacy
PubMed: 36901929
DOI: 10.3390/ijms24054500 -
European Journal of Medical Research Jun 2023Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In... (Review)
Review
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug-drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient's everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities.
Topics: Female; Humans; Aged; Everolimus; Drug Monitoring; Cytochrome P-450 CYP3A; Drug Interactions; Kidney Neoplasms
PubMed: 37381038
DOI: 10.1186/s40001-023-01172-w -
Pharmacological Reviews Apr 2021The popularity of botanical and other purported medicinal natural products (NPs) continues to grow, especially among patients with chronic illnesses and patients managed... (Review)
Review
The popularity of botanical and other purported medicinal natural products (NPs) continues to grow, especially among patients with chronic illnesses and patients managed on complex prescription drug regimens. With few exceptions, the risk of a given NP to precipitate a clinically significant pharmacokinetic NP-drug interaction (NPDI) remains understudied or unknown. Application of static or dynamic mathematical models to predict and/or simulate NPDIs can provide critical information about the potential clinical significance of these complex interactions. However, methods used to conduct such predictions or simulations are highly variable. Additionally, published reports using mathematical models to interrogate NPDIs are not always sufficiently detailed to ensure reproducibility. Consequently, guidelines are needed to inform the conduct and reporting of these modeling efforts. This recommended approach from the Center of Excellence for Natural Product Drug Interaction Research describes a systematic method for using mathematical models to interpret the interaction risk of NPs as precipitants of potential clinically significant pharmacokinetic NPDIs. A framework for developing and applying pharmacokinetic NPDI models is presented with the aim of promoting accuracy, reproducibility, and generalizability in the literature. SIGNIFICANCE STATEMENT: Many natural products (NPs) contain phytoconstituents that can increase or decrease systemic or tissue exposure to, and potentially the efficacy of, a pharmaceutical drug; however, no regulatory agency guidelines exist to assist in predicting the risk of these complex interactions. This recommended approach from a multi-institutional consortium designated by National Institutes of Health as the Center of Excellence for Natural Product Drug Interaction Research provides a framework for modeling pharmacokinetic NP-drug interactions.
Topics: Biological Products; Drug Interactions; Humans; Pharmaceutical Preparations; Reproducibility of Results
PubMed: 33712517
DOI: 10.1124/pharmrev.120.000106 -
Clinical and Translational Science Oct 2023Ciprofol (also known as HSK3486) is a promising intravenous anesthetic candidate derived from propofol and independently developed by Haisco Pharmaceutical Group Co.,...
Ciprofol (also known as HSK3486) is a promising intravenous anesthetic candidate derived from propofol and independently developed by Haisco Pharmaceutical Group Co., Ltd. (Chengdu, China). Compared with propofol, ciprofol has the potential to reduce the dose required and the associated risks. Ciprofol is extensively metabolized in vivo, and its interaction with other concurrently administered drugs during clinical application is worthy of attention. Therefore, an open-label, two-stage sequential study was performed in healthy subjects who received either a single administration of ciprofol injection or ciprofol injection after oral administration of sodium divalproex. The aim of the study was to evaluate the effects of sodium divalproex on ciprofol with respect to pharmacokinetics, pharmacodynamics, and safety, thus providing a basis for the rational clinical use of ciprofol and sodium divalproex.
Topics: Humans; Drug Interactions; East Asian People; Healthy Volunteers; Propofol; Valproic Acid
PubMed: 37537949
DOI: 10.1111/cts.13605 -
Journal of Clinical Pharmacy and... Apr 2017There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of...
WHAT IS KNOWN AND OBJECTIVE
There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults.
METHODS
This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use.
RESULTS
Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84).
WHAT IS NEW AND CONCLUSION
Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Drug Interactions; Female; Humans; Male
PubMed: 28111765
DOI: 10.1111/jcpt.12502