NIGMS Director’s Early Career Investigator Lecture on antiretrovirals, PGx

On Wednesday, April 5th at 2:00 PM EST the National Institute of General Medical Sciences (NIGMS) will broadcast the NIGMS Director’s Early Career Investigator Lecture featuring a talk by Dr. Namandjé N. Bumpus entitled “Drug Metabolism, Pharmacogenetics and the Quest to Personalize HIV Treatment and Prevention”. In it, she will discuss her work on the factors that impact metabolism and distribution of antiretrovirals and their effect on outcomes in HIV-positive individuals. Dr. Bumpus’ research attempts to integrate a mechanistic understanding of the metabolism and distribution of antiretrovirals in cells and tissues in order to enable the prediction of patient response. Dr. Bumpus is an Associate Professor of Medicine at Johns Hopkins University School of Medicine, as well as an associate editor of the journal Drug Metabolism and Disposition. 

The video cast of the lecture may be accessed below:

https://www.nigms.nih.gov/News/meetings/Pages/2017-eci.aspx

Variant and clinical annotations for antiretrovirals used in HIV treatment are available at PharmGKB. Curated pathways are also available for the following: 

• efavirenz 
• tenofovir 
• lamivudine 
• nevirapine 
• zidovudine 
• abacavir 
• nevirapine

Pharmacogenetically-guided dosing and prescribing guidelines for abacavir and atazanavir are both available at cpicpgx.org and PharmGKB.

New Paper shows pharmacogenetic testing drastically reduces ER visits and Readmissions

A new paper published in PLOSOne (Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial by Lindsay S. Elliott et al.) shows the effectiveness of precision medicine. For a year the authors followed a set of eligible patients aged 50 and over to see whether genetic testing was able to reduce hospital visits and readmissions. The testing looked at variants affecting drug responses in several pharmacogenomic genes such as CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and VKORC1, and monitored the patients phenotypes and medications. Recommendations were made to clinicians with the YouScript Clinical Decision Support Tool, and prescriptions were then altered at clinician’s discretion. The study showed a dramatic reduction; ER visits were reduced by 71%, while readmissions were reduced by 39%, when compared to a control group. This shows the usefulness of pharmacogenetics in a clinical setting.


You can read more about the genes listed above on PharmGKB (https://www.pharmgkb.org/) and the CPIC guidelines cited by this article at the CPIC website (cpicpgx.org).

Congratulations to Dr. Teri Klein!

PharmGKB is pleased to announce that the Stanford Provost has approved Dr. Teri Klein’s appointment as a Professor of Biomedical Data Science! This appointment is effective March 1 and represents a great acknowledgement of Teri’s academic contributions and leadership in data science and pharmacogenomics.  Teri and Russ Altman will remain CoPIs of PharmGKB and continue to collaborate closely on that and related projects.  Please join us in congratulating Teri!

CPIC Guideline Update: CYP2C9/VKORC1/CYP4F2 and Warfarin

The 2017 update of CPIC guideline for pharmacogenetics-guided warfarin dosing has been accepted for publication in Clinical Pharmacology and Therapeutics. CPIC extensively reviewed the literature up to Dec 2016. Both the dosing recommendations and supplemental information were updated. The accepted article can currently be viewed on the PharmGKB and CPIC websites.

The 2017 update includes the following updates and additions:

• Updated dosing recommendations based on genotypes from CYP2C9, VKORC1, CYP4F2 and rs12777823 (Fig 2)
• Added recommendation for pediatric patients (Fig 3)
• Updated evidence linking CYP2C9/VKORC1/CYP4F2 genotype to warfarin phenotype (Supplemental Table S1, S2, S3)
• Added evidence comparing pharmacogenetics warfarin dosing algorithms to standard of care dosing or clinical algorithms (Supplemental Table S4)
• Added information regarding warfarin dosing algorithms used in prospective clinical trials (Supplemental Table S5)
• Added evidence linking CYP2C9/VKORC1/CYP4F2 genotype to warfarin phenotype in pediatric patients (Supplemental Table S7)

For further details, see CPIC with further content at PharmGKB.

New PharmGKB pathway: macrolide antibiotics pharmacokinetics/pharmacodynamics

The PharmGKB summary of the pharmacokinetics and pharmacodynamics of macrolide antibiotics has been published in Pharmacogenetics and Genomics. This summary introduces the candidate genes involved in the pharmacokinetic and pharmacodynamic pathways of macrolide antibiotics, focusing on erythromycin, clarithromycin, and azithromycin. We present the uptake, transport, metabolism and clearance of the 3 macrolide antibiotics, and discuss their mechanisms of action: blocking protein translation in bacterial cells. 

A stylized illustration of the PK/PD pathways of these macrolide antibiotics accompanies the publication, using erythromycin, clarithromycin, and azithromycin to illustrate the different interactions and properties of macrolides with different chemical structures. The pathway and accompanying text can be viewed on the PharmGKB website at https://www.pharmgkb.org/pathway/PA166160731.

CPIC Guideline Summary Videos Available on PharmGKB

A new resource is available on PharmGKB to help researchers and clinicians more easily and quickly understand CPIC recommendations and how to find supporting information on the PharmGKB website. Short ~5 minute videos describe the role of the gene(s) and the impact of genetic variation on drug response, provide an overview of the genotype-phenotype terminology and classification, and summarize the CPIC recommendations for changing drug dose or drug choice based on patient diplotypes. By distilling information from the guidelines themselves and by integrating the illustrated pathways and extended dosing guidelines that are available on the PharmGKB website, these videos communicate the important relationships between each gene/drug combination. We hope the videos will help CPIC guidelines reach new audiences by providing information in a new format and that, ultimately, they will increase the use of pharmacogenetics in the clinic.

The first videos have been released and can be found on the CPIC guideline pages for codeine, clopidogrel, simvastatin, phenytoin, carbamazepine, allopurinol, and abacavir on the PharmGKB website. Over the coming weeks, summary videos describing each of the CPIC guidelines will be available through the PharmGKB YouTube channel and on each CPIC guideline page on the PharmGKB website.  We encourage you to watch and share them.

Early Registration for Precision Medicine Conference ends Sunday

Early registration for the University of Florida Precision Medicine Conference, held from March 8-10 in Orlando, Florida, ends this Sunday, January 22 at midnight. Earn continuing education credit and learn how to translate pharmacogenomics into practice. The program, which includes speakers, case studies, and participant genotyping, will provide practical information on how to individualize drug therapy, how to perform genetic testing, and how to navigate reimbursement, in addition to providing information about other emerging topics in precision medicine. The conference is open to practitioners, faculty, students, residents, and fellows.