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.