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Expert Opinion on Drug Delivery 2023The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These... (Review)
Review
INTRODUCTION
The trillions of microorganisms that comprise the gut microbiome form dynamic bidirectional interactions with orally administered drugs and host health. These relationships can alter all aspects of drug pharmacokinetics and pharmacodynamics (PK/PD); thus, there is a desire to control these interactions to maximize therapeutic efficacy. Attempts to modulate drug-gut microbiome interactions have spurred advancements within the field of 'pharmacomicrobiomics' and are poised to become the next frontier of oral drug delivery.
AREAS COVERED
This review details the bidirectional interactions that exist between oral drugs and the gut microbiome, with clinically relevant case examples outlining a clear motive for controlling pharmacomicrobiomic interactions. Specific focus is attributed to novel and advanced strategies that have demonstrated success in mediating drug-gut microbiome interactions.
EXPERT OPINION
Co-administration of gut-active supplements (e.g. pro- and pre-biotics), innovative drug delivery vehicles, and strategic polypharmacy serve as the most promising and clinically viable approaches for controlling pharmacomicrobiomic interactions. Targeting the gut microbiome through these strategies presents new opportunities for improving therapeutic efficacy by precisely mediating PK/PD, while mitigating metabolic disturbances caused by drug-induced gut dysbiosis. However, successfully translating preclinical potential into clinical outcomes relies on overcoming key challenges related to interindividual variability in microbiome composition and study design parameters.
Topics: Gastrointestinal Microbiome; Pharmaceutical Preparations; Microbiota; Probiotics
PubMed: 37405390
DOI: 10.1080/17425247.2023.2233900 -
Current Pharmaceutical Design 2023The incidences of ocular allergy have been growing with the increase in pollution. Because of challenges in new drug development, there have been efforts to maximize the... (Review)
Review
The incidences of ocular allergy have been growing with the increase in pollution. Because of challenges in new drug development, there have been efforts to maximize the efficacy of existing drugs through drug delivery approaches. The effectiveness of drugs in ophthalmic conditions is primarily determined by permeability across the barrier, corneal retention, and sustained release. Thus, there have been widespread efforts to optimize these parameters to enhance efficacy through novel formulations. This review aims to analyze the approaches to drug delivery systems to encourage further research to optimize effectiveness. With this objective, research on drug delivery aspects of anti-allergy therapeutics was included and analyzed based on formulation/drug delivery technique, Food and Drug Administration approval limits, residence time, compatibility, pre-clinical efficacy, and potential for translational application. Conventional eye drops have concerns such as poor residence time and ocular bioavailability. The novel formulations have the potential to improve residence and bioavailability. However, the use of preservatives and the lack of regulatory approval for polymers limit the translational application. The review may assist readers in identifying novel drug delivery strategies and their limitations for the development of effective ophthalmic formulations for the treatment of ocular allergy.
Topics: Humans; Administration, Ophthalmic; Drug Delivery Systems; Pharmaceutical Preparations; Cornea; Biological Availability; Hypersensitivity; Ophthalmic Solutions
PubMed: 37936454
DOI: 10.2174/0113816128275375231030115828 -
Future Cardiology Mar 2021Endovascular treatment has become first line therapy for the treatment of femoropopliteal disease. Drug-coated devices play a key role in maintaining vessel patency. In... (Review)
Review
Endovascular treatment has become first line therapy for the treatment of femoropopliteal disease. Drug-coated devices play a key role in maintaining vessel patency. In the past antiproliferative coating of drug-coated balloons (DCBs) exclusively consisted of paclitaxel. Use of limus drugs was limited by a short residency time in the vessel wall. Besides the drug, the SELUTION SLR™ drug-eluting balloon system consists of a coating formulation of four excipients. The first excipient is a biodegradable polymer (poly(lactic-co-glycolic acid)) that is intermixed with the sirolimus to form micro-reservoirs and regulates drug release via matrix degradation. This review summarizes the existing pre-clinical and clinical literature on treatment of femoropopliteal artery lesions with the SELUTION SLR DCB.
Topics: Angioplasty, Balloon; Coated Materials, Biocompatible; Drug-Eluting Stents; Humans; Peripheral Arterial Disease; Pharmaceutical Preparations; Popliteal Artery; Treatment Outcome
PubMed: 32815739
DOI: 10.2217/fca-2020-0085 -
Annales D'endocrinologie Sep 2019Adrenal incidentaloma refers to an asymptomatic adrenal mass detected through an imaging procedure performed for reasons unrelated to adrenal dysfunction or suspected... (Review)
Review
Adrenal incidentaloma refers to an asymptomatic adrenal mass detected through an imaging procedure performed for reasons unrelated to adrenal dysfunction or suspected dysfunction. In general, adrenal incidentalomas are non-functioning adrenal adenomas, but in some cases, may require therapeutic intervention: eg., adrenocortical carcinoma, pheochromocytoma, primary aldosteronism, cortisol hypersecretion, or adrenal insufficiency. Hormone assessment is crucial to characterize adrenal incidentaloma. Nowadays, various hormone assay methods are available, such as immunoassay and mass spectrometry. However, there are several pitfalls that should be considered: e.g., circadian rhythm, gender/age dependency, preanalytical and analytical issues, and drug interactions. Pharmacological or analytical interference can lead to false serum concentrations and may result in misinterpretation of results and thus inappropriate treatment. The purpose of this review was to study the main interferences that may be observed in the different tumor types of adrenal incidentalomas in order to help physicians in their clinical decision-making and for the overall benefit of patients.
Topics: Adrenal Gland Neoplasms; Artifacts; Clinical Laboratory Techniques; Diagnostic Techniques, Endocrine; Drug Contamination; Equipment Contamination; Hormones; Humans; Hydrocortisone; Incidental Findings; Pharmaceutical Preparations; Pituitary-Adrenal Function Tests; Pre-Analytical Phase
PubMed: 31445667
DOI: 10.1016/j.ando.2018.11.006 -
Zeitschrift Fur Evidenz, Fortbildung... Nov 2021Hospital stays are often associated with medication changes, which may lead to drug-related problems (DRPs). Medication reconciliation and medication reviews are...
BACKGROUND
Hospital stays are often associated with medication changes, which may lead to drug-related problems (DRPs). Medication reconciliation and medication reviews are strategies to detect and resolve DRPs.
METHODS
A descriptive cohort study was conducted using DRPs collected during routine pharmacist-led medication reconciliation and medication reviews in the hospital's community pharmacy at discharge (Zug Cantonal Hospital, Switzerland). In a simulation experiment, we retrospectively analysed the detection and resolution possibilities of these DRPs and their dependency on different information sources.
RESULTS
Overall, 6,087 prescriptions were filled in the hospital's community pharmacy (between June 2016 and May 2019). Among 1,352 prescriptions (with ≥ 1 documented DRP) a total of 1,876 DRPs were detected. The retrospective assessment showed that 1,115 DRPs could have been detected by performing simple medication reviews (based on the discharge prescription and the medication history), whereas in the remaining cases, additional clinical and/or patient-specific information would have been needed. In 944 (84.7 %) DRPs, which are detectable by simple medication reviews, the pharmacist would need to consult the prescriber for resolution.
CONCLUSION
The detection of DRPs is strongly influenced by the information available. These results support models with pre-discharge medication reconciliation and pharmacist-led medication review procedures enabling both comprehensive detection and facilitated resolution of DRPs.
Topics: Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Germany; Hospitals; Humans; Medication Reconciliation; Patient Discharge; Pharmaceutical Preparations; Retrospective Studies
PubMed: 34538579
DOI: 10.1016/j.zefq.2021.08.004 -
Acta Parasitologica Dec 2022Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess... (Review)
Review
PURPOSE
Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess anti-inflammatory and anti-apoptotic activity, immunomodulatory action, as well as regenerative properties. Since MSCs also have antimicrobial properties, it has been suggested that they should be utilized for treating infectious diseases. In this study, the last pre-clinical advances in the efficacy of MSCs' therapy against parasitic diseases were reviewed.
METHODS
Data about the effects of MSCs' therapy on experimental and pre-clinical parasitic infections were collected by searching relevant articles and reviewing them.
RESULTS
In the present study, empirical findings on the impacts of MSCs' therapy against parasitic diseases were recapitulated. Studies have reported that the administration of MSCs reduces the burden of the parasite and modulates the levels of inflammatory and anti-inflammatory cytokines in parasitic diseases, including schistosomiasis, malaria, cystic echinococcosis, toxocariasis, leishmaniasis, and trypanosomiasis. Also, the administration of MSCs combined with anti-parasitic drugs enhanced anti-parasitic effects and immunomodulatory actions.
CONCLUSION
Based on this review, empirical studies have revealed the beneficial effects of MSCs against some parasitic infections. This new therapeutic strategy showed both anti-parasitic and immunomodulatory effects. Also, the combination of anti-parasitic drugs with MSCs' therapy promoted anti-parasitic and immunomodulatory activities against parasitic infections.
Topics: Animals; Humans; Parasites; Pharmaceutical Preparations; Mesenchymal Stem Cells; Immunomodulation; Parasitic Diseases
PubMed: 36280646
DOI: 10.1007/s11686-022-00620-7 -
Journal of Oncology Pharmacy Practice :... Jan 2022Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to...
Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy - = 4) and drug therapy problems four (dosage too low - = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.
Topics: Brazil; Humans; Iodine Radioisotopes; Pharmaceutical Preparations; Pharmacy; Pharmacy Service, Hospital
PubMed: 34661492
DOI: 10.1177/10781552211045361 -
Clinical Therapeutics Feb 2024Emeritus Editor-in-Chief, Richard Shader, published 2 editorials in 2014 to state that Clinical Therapeutics' would no longer consider simple innovator vs generic...
INTRODUCTION
Emeritus Editor-in-Chief, Richard Shader, published 2 editorials in 2014 to state that Clinical Therapeutics' would no longer consider simple innovator vs generic bioequivalence studies for publication and would require a rationale for the choice of agents when submitting drug-drug interaction studies for consideration. The intervening decade of developments in this field provides an opportunity to comment on these trends. Lewis Scheiner anchors the subsequent discussion in a "Learn and Confirm" super-structure of thinking about the goals of early development of pharmaceutical agents. Subsequent experience with newer agents that are focused on immunological targets has led to a shift from the simple No Observable Effect Level (NOEL) model to the Minimal Anticipated Biological Effect Level (MABEL) model for biologically focused effects to assess pre-clinical data in guiding the selection of a starting dose for First-in-Human studies.
ELEMENTS OF PHASE I STUDIES
The primary tasks of Phase I activities are to describe the pharmacokinetics (determination of absorption, distribution, metabolism, and excretion) and essential pharmacodynamics (the dose correlation with the physiological responses, plus any untoward effects, including idiosyncratic responses) keeping in mind reporting requirements. Other Phase I activities usually conducted later in the development cycle include evaluation of drug interactions with food and other pharmaceutical agents and thorough QT studies.
INNOVATIONS
Phase I studies have been evolving in response to the unrelenting pressures to improve access and efficiencies in time, cost, and effort. Changes have been occurring in the characteristics of the participating populations, the starting dose, and shifts in the enrollment schedule to a more flexible, data-driven, adaptive design.
ISSUES
Additional issues have gained attention in the recent past, including Phase 0/microdosing, use of Phase I studies explicitly for treatment in the case of oncological products, involvement of Data Safety Monitoring Committees especially for first-in-class molecules, and improved means of optimizing selection of candidate agents for advancement to subsequent stages of development. Of final importance is the need for greater transparency of the presently inaccessible, early development study data maintained in commercial corporate legacy databases. Taken together, these developments and innovations by a broad range of stakeholders point to continuing opportunities for clinical investigators to explore the potential of Phase I studies to contribute to their own specialties.
Topics: Humans; Research Design; Therapeutic Equivalency; Pharmaceutical Preparations
PubMed: 38342708
DOI: 10.1016/j.clinthera.2024.01.002 -
Artificial Intelligence in Medicine Sep 2021Drug-Drug Interaction (DDI) extraction is the task of identifying drug entities and the potential interactions between drug pairs from biomedical literature....
Drug-Drug Interaction (DDI) extraction is the task of identifying drug entities and the potential interactions between drug pairs from biomedical literature. Computer-aided extraction of DDIs is vital for drug discovery, as this process remains extremely expensive and time consuming. Therefore, Machine Learning-based approaches can reduce the laborious task during the drug development cycle. Numerous traditional and Neural Network-based approaches for Drug Named Entity Recognition (DNER) and the classification of DDIs have been proposed over the years. However, despite the development of many effective methods, achieving good prediction accuracy is an area where significant improvement can be made. In this article, we present a novel end-to-end approach that tackles the overall DDI extraction task as a pipelined method via the Transformer model architecture and biomedical domain pre-trained weights. In our approach, the tasks of DNER and DDI classification are executed successively to extract the drug entities and to classify their relationship respectively. The proposed approach, TP-DDI, integrates prior knowledge by using pre-trained weights from BioBERT and improves in both the Drug Named Entity Recognition and the overall DDI extraction task over the current state-of-the-art approaches on the DDI Extraction 2013 corpus.
Topics: Data Mining; Drug Interactions; Machine Learning; Neural Networks, Computer; Pharmaceutical Preparations
PubMed: 34531012
DOI: 10.1016/j.artmed.2021.102153 -
Current Pharmaceutical Design 2020Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical... (Review)
Review
Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical properties of existing active pharmaceutic ingredients (APIs) without compromising their therapeutic benefits. Over time, it has become an integral part of the pre-formulation stage of drug development because of its ability to yield cocrystals with improved properties in a way that other traditional methods cannot easily achieve. Cocrystals are solid crystalline materials composed of two or more than two molecules which are non-covalently bonded in the same crystal lattice. Due to the continuous efforts of pharmaceutical scientists and crystal engineers, today cocrystals have emerged as a cutting edge tool to modulate poor physicochemical properties of APIs such as solubility, permeability, bioavailability, improving poor mechanical properties and taste masking. The success of cocrystals can be traced back by looking at the number of products that are getting regulatory approval. At present, many cocrystals have obtained regulatory approval and they successfully made into the market place followed by a fair number of cocrystals that are currently in the clinical phases. Considering all these facts about cocrystals, the formulation scientists have been inspired to undertake more relevant research to extract out maximum benefits. Here in this review cocrystallization technique will be discussed in detail with respect to its background, different synthesis approaches, synthesis mechanism, application and improvements in drug delivery systems and its regulatory perspective.
Topics: Biological Availability; Crystallization; Permeability; Pharmaceutical Preparations; Solubility
PubMed: 32691702
DOI: 10.2174/1381612826666200720114638