scholarly journals Pharmacogenomic landscape of COVID-19 therapies from Indian population genomes

2021 ◽  
Author(s):  
S Sahana ◽  
Ambily Sivadas ◽  
Mohit Mangla ◽  
Abhinav Jain ◽  
Rahul C Bhoyar ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Safety ◽  
Validation Studies ◽  
Metabolic Disorder ◽  
Indian Population ◽  
Direct Evidence ◽  
Gene Interactions ◽  
Ethnic Populations ◽  
Whole Genomes ◽  
Clinically Significant

Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug–gene (pharmacogenetic), drug–drug and drug–drug–gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug–drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.

Drug-Drug Interaction Signal Detection from Drug Safety Reports

2018 ◽  
Author(s):  
Brian Zylich ◽  
Brian McCarthy ◽  
Andrew Schade ◽  
Huy Tran ◽  
Xiao Qin ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Signal Detection ◽  
Drug Safety ◽  
Drug Drug Interaction

Inhibition of Hepatic Microsomal Drug Metabolism by the Hydrazines Ro 4-4602, MK 486, and Procarbazine Hydrochloride

1972 ◽  
Vol 50 (7) ◽  
pp. 721-724 ◽  
Author(s):  
Norman R. Bade ◽  
Stuart M. MacLeod ◽  
Kenneth W. Renton
Keyword(s):  
Drug Interaction ◽  
Drug Metabolism ◽  
Sleeping Time ◽  
Hydrazine Derivatives ◽  
Significant Drug Interaction ◽  
Microsomal Drug Metabolism ◽  
Clinically Significant ◽  
Hepatic Biotransformation

Preliminary experiments were undertaken to examine the effect of three hydrazine derivatives, viz. Ro 4-4602, MK 486, and procarbazine hydrochloride, on hepatic microsomal drug metabolism in rats. All three compounds when given as pretreatment significantly prolonged pentobarbital sleeping time. In vitro, the hepatic microsomal N-demethylation of aminopyrine was inhibited. It is concluded that all three drugs are possible sources of clinically significant drug interaction when administered in combination with other agents which undergo hepatic biotransformation.

scholarly journals ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Liam K. R. Sharkey ◽  
Thomas A. Edwards ◽  
Alex J. O’Neill
Keyword(s):  
Antibiotic Resistance ◽  
Direct Evidence ◽  
New Drugs ◽  
Bacterial Ribosome ◽  
Broad Array ◽  
Clinically Significant ◽  
Antibiotic Efflux ◽  
Dose Dependent ◽  
Ribosomal Protection

ABSTRACTMembers of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro. To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition.

Lack of a Clinically Significant Pharmacokinetic Drug Interaction Between Tiagabine and Valproate

1998 ◽  
Vol 5 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Linda E. Gustavson ◽  
Kenneth W. Sommerville ◽  
Galen F. Witt ◽  
Helen J. Guenther ◽  
G. Richard Granneman ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Pharmacokinetic Drug Interaction ◽  
Clinically Significant ◽  
Pharmacokinetic Drug

scholarly journals Lack of a clinically significant drug-drug interaction in healthy volunteers between the HCV protease inhibitor boceprevir and the proton pump inhibitor omeprazole

2013 ◽  
Vol 68 (6) ◽  
pp. 1415-1422 ◽  
Author(s):  
C. T. M. M. de Kanter ◽  
A. P. H. Colbers ◽  
M. I. Blonk ◽  
C. P. W. G. M. Verweij-van Wissen ◽  
B. J. J. W. Schouwenberg ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Proton Pump Inhibitor ◽  
Protease Inhibitor ◽  
Healthy Volunteers ◽  
Proton Pump ◽  
Hcv Protease ◽  
Drug Drug Interaction ◽  
Clinically Significant

Enhancement of Warfarin Response in a Patient Receiving Etoposide and Carboplatin Chemotherapy

1997 ◽  
Vol 31 (9) ◽  
pp. 1006-1008 ◽  
Author(s):  
Alyssa T Le ◽  
Noelle K Hasson ◽  
Bert L Lum
Keyword(s):  
Drug Interaction ◽  
Time Course ◽  
International Normalized Ratio ◽  
Average Dose ◽  
Concomitant Disease ◽  
Close Monitoring ◽  
Mixed Germ Cell Tumor ◽  
Monitoring Strategies ◽  
Altered Response ◽  
Clinically Significant

Objective To report a case of a possible drug interaction between warfarin, carboplatin, and etoposide resulting in a marked increase in a patient's response to warfarin, and to outline monitoring strategies for this interaction. Case Summary A 74-year-old white man receiving warfarin (average dose 42.5 mg/wk) for atrial fibrillation was diagnosed with a right testicular non-seminoma mixed germ cell tumor. Mediastinal metastases were subsequently discovered, and the patient was treated with a chemotherapy regimen including carboplatin and etoposide. Sixteen days after the first course of chemotherapy, the international normalized ratio (INR) was increased to 12.6 from a baseline range of 1.15–2.11 that was observed over the previous 8 months of therapy, indicating a clinically significant alteration in the pharmacodynamic response to warfarin. Discussion This patient had no concomitant disease or dietary changes to explain the altered response to warfarin. Carboplatin and etoposide have not been reported to inhibit warfarin metabolism. However, previous reports have suggested that etoposide may displace warfarin from its protein binding sites, resulting in an early elevation in prothrombin time following chemotherapy. The late elevation of INR observed in our patient suggests that his response to warfarin may have been due to the displacement of warfarin by elemental platinum, which has a long plasma half-life. Conclusions This case report suggests a possible drug interaction between carboplatin, etoposide, and warfarin. Because of the risk associated with an increased response to warfarin, we recommend close monitoring of the INR, perhaps twice weekly, early and later in the time course following chemotherapy with these agents. Appropriate dosage adjustments of warfarin should be performed if an altered response to warfarin is observed.

scholarly journals Coccygeal Morphology on Multislice Computed Tomography in a Tertiary Hospital in India

2017 ◽  
Vol 11 (5) ◽  
pp. 694-699 ◽  
Author(s):  
Venkatraman Indiran ◽  
Vadivalagianambi Sivakumar ◽  
Prabakaran Maduraimuthu
Keyword(s):  
Computed Tomography ◽  
Indian Population ◽  
Normal Population ◽  
Tertiary Hospital ◽  
Cross Sectional Study ◽  
Ct Scans ◽  
Type I ◽  
Cross Sectional ◽  
Ethnic Populations ◽  
The Mean

<sec><title>Study Design</title><p>A retrospective, cross-sectional study of 213 patients who presented for abdominal computed tomography (CT) scans to assess coccygeal morphology in the Indian population.</p></sec><sec><title>Purpose</title><p>There have been relatively few studies of coccygeal morphology in the normal population and none in the Indian population. We aimed to estimate coccygeal morphometric parameters in the Indian population.</p></sec><sec><title>Overview of Literature</title><p>Coccygeal morphology has been studied in European, American, Korean, and Egyptian populations, with few differences in morphology among populations.</p></sec><sec><title>Methods</title><p>A retrospective analysis of 213 abdominal CT scans (114 males and 99 females; age, 7–88 years; mean age, 47.3 years) was performed to evaluate the number of coccygeal segments, coccyx type, sacrococcygeal and intercoccygeal fusion and subluxation, coccygeal spicules, sacrococcygeal straight length, and sacrococcygeal and intercoccygeal curvature angles. Results were analyzed for differences in morphology with respect to sex and coccyx type.</p></sec><sec><title>Results</title><p>Types I and II coccyx were the most common. Most subjects had four coccygeal vertebrae; 93 subjects (43.66%) had partial or complete sacrococcygeal fusion. Intercoccygeal fusion was common, occurring in 193 subjects. Eighteen subjects had coccygeal spicules. The mean coccygeal straight length was 33.8 mm in males and 31.5 mm in females; the mean sacrococcygeal curvature angle was 116.6° in males and 111.6° in females; the mean intercoccygeal curvature angle was 140.94° in males and 145.10° in females.</p></sec><sec><title>Conclusions</title><p>Type I was the most common coccyx type in our study, as in Egyptian and Western populations. The number of coccygeal vertebrae and prevalence of sacrococcygeal and intercoccygeal fusion in the Indian population were similar to those in the Western population. The mean coccygeal straight length and mean sacrococcygeal curvature angle were higher in males, whereas the intercoccygeal curvature angle was higher in females. Information on similarities and differences in coccygeal morphology between different ethnic populations could be useful in imaging and treating patients presenting with coccydynia.</p></sec>

MHRA Drug Safety Update: denosumab (Xgeva) and rebound hypercalcaemia

2018 ◽  
Vol 56 (12) ◽  
pp. 142-142 ◽  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Drug Safety ◽  
Regulatory Agency ◽  
Cell Tumor ◽  
Clinically Significant ◽  
Medical And Healthcare

Review of: Medical and Healthcare products Regulatory Agency. Denosumab for giant cell tumor of bone: risk of clinically significant hypercalcaemia following discontinuation. Drug Safety Update 2018;11(11);2.

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