Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on Small-Molecule Drug Metabolism Through the Cytochrome P450 System

2021 ◽  
pp. 106002802110222
Author(s):  
C. Michael White ◽  
Dakota J. Sicignano ◽  
Kimberly Smith
Keyword(s):  
Cytochrome P450 ◽  
Clinical Practice ◽  
Steady State ◽  
Drug Metabolism ◽  
Small Molecule ◽  
Human Subjects ◽  
Biological Drugs ◽  
Minimal Impact ◽  
Biological Drug ◽  
The Impact

Objective: Assess the impact of interferons and interleukin (IL)-2 and IL-6 inhibitors on cytochrome P450 (CYP) drug metabolism in human subjects. Data Sources: PubMed search from 1980 to March 31, 2021, limited to human subjects and English language via search strategy: (biological drug names) [AND] (cytochrome [OR] CYP metabolism). Study Selection and Data Extraction: Narrative review of human studies assessing biological drugs in select classes that affect CYP drug metabolism. Data Synthesis: Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine). Relevance to Patient Care and Clinical Practice: Patients using interferons, IL-2, or IL-6 blocking drugs at steady state with CYP substrates could have altered drug metabolism and experience adverse events. With interferons and biological anti-inflammatory drugs, some isoenzymes will be inhibited, whereas others will be enhanced, and the magnitude of the effect can sometimes be significant. In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient’s entire disease and medication profile when determining risk/benefit of treatment. Conclusions: Interferon therapy or inflammatory suppression via IL-2 or IL-6 can alter steady-state concentrations of CYP-metabolized small-molecule drugs.

Inflammation Suppresses Patients’ Ability to Metabolize Cytochrome P450 Substrate Drugs

2021 ◽  
pp. 106002802110478
Author(s):  
C. Michael White
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Bacterial Infections ◽  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Therapeutic Index ◽  
Biologic Drugs ◽  
Markers Of Inflammation ◽  
The Impact

Objective: To assess the impact of inflammation on cytochrome P450 (CYP) drug metabolism in human subjects. Data Sources: A PubMed search was done from 1980 to July 2021 limited to human subjects and English language using a search strategy of (((phase I metabolism) OR (CYP) OR (cytochrome P450)) AND (inflammatory OR inflammation)). Study Selection and Data Extraction: Narrative review of human studies assessing the impact of inflammation or inflammatory suppression with biologic drugs on CYP drug metabolism were used. Data Synthesis: Patients with inflammatory conditions ranging from fungal, viral, or bacterial infections to noninfectious causes (critical illness, surgical procedure, cancer, or transplantation of stem cells or organs) have suppressed drug metabolism. Markers of inflammation such as C-reactive protein or α-1-acid glycoprotein are correlated with reduced clearance through CYP3A4, CYP1A2, and CYP2C19. Elevated interleukin-6 concentrations are also associated or correlated with reduced clearance for CYP3A4 and CYP2C-19 isoenzymes. There was insufficient information to properly assess CYP2D6. Relevance to Patient Care and Clinical Practice: Health professionals should appreciate that patients with acute or chronic inflammation from infectious or noninfectious causes could have suppressed drug metabolism through CYP3A4, CYP1A2, and CYP2C19. For narrow therapeutic index drugs, such as many of the drugs assessed in this review, that means more judicious drug monitoring to prevent adverse events. Conclusions: Like other types of drug-drug or drug-disease interactions, inflammation can alter the steady-state concentration of CYP metabolized drugs.

scholarly journals Undertaking Procedure-Based Assessment is Feasible in Clinical Practice

2009 ◽  
Vol 91 (2) ◽  
pp. 110-112 ◽  
Author(s):  
K James ◽  
K Cross ◽  
ME Lucarotti ◽  
AL Fowler ◽  
TA Cook
Keyword(s):  
Clinical Practice ◽  
Pilot Study ◽  
Anterior Resection ◽  
Assessment Tool ◽  
Right Hemicolectomy ◽  
Time Constraints ◽  
Main Study ◽  
Minimal Impact ◽  
The Impact ◽  
Colorectal Procedures

INTRODUCTION With the development of a new curriculum, workplace based assessments such as procedure-based assessment (PBA) are becoming increasingly common within surgical training. However, there have been concerns about the impact of these assessments on clinical practice. This study assessed the time taken to complete PBA forms to determine whether it is feasible in clinical practice. MATERIALS AND METHODS PBAs for three colorectal procedures (anterior resection, right hemicolectomy and anal fistula) were undertaken by various trainers and trainees. A pilot study was performed to identify potential reasons for incomplete forms and procedural modifications subsequently applied in the main study. Times taken to complete the consenting and operative components of the forms were recorded. RESULTS Incomplete forms in the pilot were mainly attributable to time constraints. In the main study, all assessments were completed within 30 min. Assessment times increased with complexity of the procedure. Median times for completing the consenting and operative components in anterior resection were 13 min (range, 8–15 min) and 15 min (range, 10–18 min), respectively. CONCLUSIONS PBAs are feasible in clinical practice and are valued by trainees as a means of enabling focused feedback and targeted training. Commitment from trainers and trainees will be required but, with adequate planning, the assessment tool is effective with minimal impact on clinical practice.

scholarly journals How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

2016 ◽  
Vol 67 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Valon Krasniqi ◽  
Aleksandar Dimovski ◽  
Iva Klarica Domjanović ◽  
Ivan Bilić ◽  
Nada Božina
Keyword(s):  
Cytochrome P450 ◽  
Clinical Practice ◽  
Drug Metabolism ◽  
Metabolic Pathways ◽  
Adverse Reactions ◽  
Interindividual Variability ◽  
Drug Reactions ◽  
Increased Risk ◽  
Cytochrome P450 Genes ◽  
Drug Efficiency

Abstract Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.

scholarly journals Effects of Wine Components in Inflammatory Bowel Diseases

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5891
Author(s):  
Josip Vrdoljak ◽  
Marko Kumric ◽  
Tina Ticinovic Kurir ◽  
Ivan Males ◽  
Dinko Martinovic ◽  
...  
Keyword(s):  
Large Scale ◽  
Human Subjects ◽  
Current Evidence ◽  
Biological Drugs ◽  
Biological Compounds ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Natural Foods ◽  
The Impact

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1–2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.

Translating Principles of Speech Science to Clinical Practice: Current and Future Trends in Craniofacial Disorders

2008 ◽  
Vol 18 (1) ◽  
pp. 31-40 ◽  
Author(s):  
David J. Zajac
Keyword(s):  
Clinical Practice ◽  
Speech Intelligibility ◽  
Current Practice ◽  
Computer Assisted ◽  
Behavioral Management ◽  
Single Word ◽  
Future Directions ◽  
Speech Science ◽  
The Impact ◽  
Opinion Article

Abstract The purpose of this opinion article is to review the impact of the principles and technology of speech science on clinical practice in the area of craniofacial disorders. Current practice relative to (a) speech aerodynamic assessment, (b) computer-assisted single-word speech intelligibility testing, and (c) behavioral management of hypernasal resonance are reviewed. Future directions and/or refinement of each area are also identified. It is suggested that both challenging and rewarding times are in store for clinical researchers in craniofacial disorders.

A Generic Model of Clinical Practice

2003 ◽  
Vol 42 (03) ◽  
pp. 203-211 ◽  
Author(s):  
J. L. G. Dietz ◽  
A. Hasman ◽  
P. F. de Vries Robbé ◽  
H. J. Tange
Keyword(s):  
Clinical Practice ◽  
Theoretical Model ◽  
Action Theory ◽  
Human Subjects ◽  
Shared Care ◽  
Patient Record ◽  
Generic Model ◽  
Problem Solver ◽  
Record Keeping ◽  
Process View

Summary Objectives: Many shared-care projects feel the need for electronic patient-record (EPR) systems. In absence of practical experiences from paper record keeping, a theoretical model is the only reference for the design of these systems. In this article, we review existing models of individual clinical practice and integrate their useful elements. We then present a generic model of clinical practice that is applicable to both individual and collaborative clinical practice. Methods: We followed the principles of the conversation-for-action theory and the DEMO method. According to these principles, information can only be generated by a conversation between two actors. An actor is a role that can be played by one or more human subjects, so the model does not distinguish between inter-individual and intra-individual conversations. Results: Clinical practice has been divided into four actors: service provider, problem solver, coordinator, and worker. Each actor represents a level of clinical responsibility. Any information in the patient record is the result of a conversation between two of these actors. Connecting different conversations to one another can create a process view with meta-information about the rationale of clinical practice. Such process view can be implemented as an extension to the EPR. Conclusions: The model has the potential to cover all professional activities, but needs to be further validated. The model can serve as a theoretical basis for the design of EPR-systems for shared care, but a successful EPR-system needs more than just a theoretical model.

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