Saturday, February 18, 2017

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!

Wednesday, February 15, 2017

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.

Wednesday, February 8, 2017

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.

Monday, January 23, 2017

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.

Friday, January 20, 2017

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.

Wednesday, December 14, 2016

CPIC Guideline Update: CYP2D6, CYP2C19 and tricyclic antidepressants (TCAs)

The 2016 update of the guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) regarding the use of pharmacogenetic tests for CYP2D6 and CYP2C19 in dosing tricyclic antidepressants (TCAs) have been accepted for publication in Clinical Pharmacology and Therapeutics. The accepted article can currently be viewed on the PharmGKB and CPIC websites. 

TCAs are mixed serotonin and norepinephrine reuptake inhibitors used to treat depression and several other disease states.
The 2016 guideline update provides dosing recommendations:
  • for TCAs based on CYP2D6 phenotype
  • for TCAs based on CYP2C19 phenotype
  • for amitriptyline based on both CYP2D6 and CYP2C19 phenotype.
Amitriptyline and nortriptyline are used as representative TCAs because the majority of pharmacogenomics studies have been published on these drugs. However, TCAs have comparable pharmacokinetic properties and it it may be reasonable to apply the recommendations to other TCAs.

For further details see the guidelines and supplement at PharmGKB and CPIC.

Thursday, December 8, 2016

New CPIC Guideline - CYP2C19 and voriconazole

Guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) regarding the use of pharmacogenetic tests of CYP2C19 for voriconazole prescribing decisions have been accepted for publication in Clinical Pharmacology and Therapeutics. The accepted article can currently be viewed on the PharmGKB or CPIC websites.

Voriconazole is a triazole antifungal agent active against a variety of fungi and molds, such as Candida, Aspergillus, Fusarium and Cryptococcous. However, it is particularly recommended for pulmonary invasive aspergillosis, an infection that primarily occurs in immunocompromised patients. CYP2C19 is the primary enzyme responsible for the metabolism of voriconazole, and variations within the CYP2C19 gene have been shown to affect exposure to voriconazole. CYP2C19 ultrarapid or rapid metabolizers may have decreased voriconazole exposure, affecting the ability to achieve therapeutic concentrations, while poor metabolizers may have increased exposure, affecting the risk for adverse effects.

For therapeutic recommendations and further details, please refer to the CPIC Guideline for CYP2C19 and Voriconazole Therapy on the PharmGKB or CPIC websites.