Recent Case Studies of Clinically Significant Drug–Drug Interactions and the Limits ofIn Vitro Prediction Methodology

2007 ◽  
pp. 195-200
Author(s):  
Ren H. Levy ◽  
Isabelle Ragueneau-Majlessi ◽  
Carol Collins
Keyword(s):  
Drug Interactions ◽  
Case Studies ◽  
Recent Case ◽  
Clinically Significant

scholarly journals Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

2020 ◽  
Vol 75 (12) ◽  
pp. 3417-3424 ◽  
Author(s):  
Catherine Hodge ◽  
Fiona Marra ◽  
Catia Marzolini ◽  
Alison Boyle ◽  
Sara Gibbons ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Herbal Medicines ◽  
Qt Prolongation ◽  
Critically Ill Patient ◽  
Experimental Drugs ◽  
Mesh Terms ◽  
Experimental Therapies ◽  
Clinically Significant ◽  
Novel Coronavirus

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

scholarly journals A Note on Distributions of True versus Fabricated Data

1996 ◽  
Vol 83 (3) ◽  
pp. 776-778 ◽  
Author(s):  
Theodore P. Hill
Keyword(s):  
Empirical Evidence ◽  
Case Studies ◽  
Goodness Of Fit ◽  
Recent Case ◽  
Benford’S Law ◽  
Accounting Data ◽  
Goodness Of Fit Tests ◽  
Benford's Law

New empirical evidence and statistical derivations of Benford's Law have led to successful goodness-of-fit tests to detect fraud in accounting data. Several recent case studies support the hypothesis that fabricated data do not conform to expected true digital frequencies.

Human Factors in Architecture: A View from the Field

1982 ◽  
Vol 26 (2) ◽  
pp. 203-203
Author(s):  
James A. Wise
Keyword(s):  
Built Environment ◽  
Human Factors ◽  
Case Studies ◽  
Real World ◽  
Architectural Design ◽  
Recent Case ◽  
Panel Session ◽  
Real World Problems

This is a panel session focused on the applications of Human Factors to real world problems in architectural design. Five representatives from various design & research professions will present recent case studies of theirs, and examine the contribution that Human Factors made to these projects. The diversity of their examples shows the usefulness and importance on integrating concerns for the human user into plans for the built environment.

Setting Boundaries: Lessons on When to Not Make Theatre

2019 ◽  
Author(s):  
Allie Fenwick
Keyword(s):  
Case Studies ◽  
School Board ◽  
Catholic School ◽  
Recent Case ◽  
Open Letter ◽  
Educational Impact ◽  
Proposed Model ◽  
Common Thread ◽  
Artistic Freedom ◽  
Adequate Representation

A common thread throughout much of Canada’s current theatrical output is that it asks audiences to think deeply about themselves and their connection to the material. Working with the idea that theatre has an important social and educational impact, my essay examines the need to set boundaries for theatre content. These boundaries are meant to function as a set of guidelines for managing controversial artistic choices, especially in a culture where artistic freedom and productive controversy are at stake. Some of the criteria I have developed for how to set boundaries include: how the work represents its subjects; what Canadians see as taboo; personal limitations individuals set for themselves; and, contentious timing. My research examines recent case studies, starting with Robert Lepage’s Kanata, which aimed to discuss Canada’s settler history, however, was cancelled in Canada after Indigenous artists and activists wrote an open letter concerning the lack of Indigenous presence in the cast and production team. I then move to an example that challenges my proposed model with Prom Queen: The Musical, a play about an Ontario student and his boyfriend battling the Catholic school board to go to prom together. I argue that although the play may not represent the values of the school board, adequate representation of the board’s ideals should be disregarded due to their anti-LGBTQ2+ beliefs. Through these examples and more, my research found that there are certain boundaries that should not be crossed in theatre. However, determining where these boundaries are situated remains in constant negotiation.

Drug Interactions of Macrolides: Emphasis on Dirithromycin

1997 ◽  
Vol 31 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Vish S Watkins ◽  
Ron E Polk ◽  
Jennifer L Stotka
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Ethinyl Estradiol ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
Kidney Transplant Recipients ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Clinically Significant

Objective To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. Data Sources A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. Data Synthesis Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug–drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug–drug interactions. Conclusions Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

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