Wednesday, May 28, 2014

Tramadol pathway summary published in PG&G

Tramadol is a centrally acting opioid analgesic used to relieve moderate to severe pain.  It is administered as a racemic mixture of (+) and (-) enantiomers and exerts its analgesic effect via activating the µ-opioid receptor and inhibiting the neurotransmitter reuptake. Tramadol metabolism to its major active metabolite O-desmethyl tramadol (M1) is predominantly mediated via CYP2D6. Genetic variations of CYP2D6 have been shown to affect not only the pharmacokinetics of tramadol and M1, but also the analgesic efficacy as well as pharmacodynamic responses.

We have published the
PharmGKB summary: tramadol pathway in the Pharmacogenetics and Genomics Journal. This review summarizes the metabolism and transport of tramadol and discusses genetic variations affecting the pharmacokinetics, efficacy and toxicity of tramadol and their clinical significance.

Find out more...
View our Tramadol pathway on PharmGKB.

Read our new publication: 
PharmGKB summary:tramadol pathway
Gong L, Stamer UM, Tzvetkov MV, Altman RB, Klein TE.
Pharmacogenet Genomics. 2014 May 20. [Epub ahead of print]
PMID: 24849324

View all pathways on PharmGKB.

Wednesday, May 21, 2014

Big Data Conference 2014

Stanford University are hosting the second Big Data in Biomedicine conference this week, featuring speakers across academia, industry and government.

PharmGKB's Associate Director will be discussing Genomic Medicine on Friday 23rd May with other speakers leading in this field.

Watch the live stream of the Big Data in Biomedicine talks.

Monday, May 12, 2014

Update: CPIC ivacaftor-CFTR guideline

The CPIC guideline for ivacaftor treatment based on CFTR genotype has been updated on PharmGKB, in light of changes to the FDA-approved drug label.

Originally, ivacaftor was indicated only in patients with the G551D variant. This has now been extended to other variants that result in CFTR gating defects:

> View the updated CPIC ivacaftor-CFTR guideline.
Figure 1: Treatment algorithm for clinical use of ivacaftor for cystic fibrosis patients based on CFTR genotype.

Tuesday, May 6, 2014

New CPIC Guideline: G6PD & Rasburicase

CPIC has published therapeutic guidelines for rasburicase based on G6PD genotype.

Rasburicase is a drug that lowers uric acid levels and is used to treat or prevent hyperuricemia in cancer patients undergoing chemotherapy, and in newborns to prevent kidney damage. It is contraindicated for use in patients with G6PD deficiency due to an increased risk of acute hemolytic anemia and possibly also methemoglobinemia. Reduced G6PD enzyme activity is caused by underlying genetic variants in the G6PD gene. There are more than 180 G6PD variants, each categorized class I to V depending on the level of deficiency in red blood cells conferred and the associated resulting clinical manifestations.  

To our knowledge, this is the first published guideline to fully address therapeutic recommendations for patients who have pre-emptive G6PD genotyping or sequencing results in both men and women, for a large collection of variants.

CPIC contraindicate the use of rasburicase in males or females who are hemi/homozygous for class I-III G6PD variants, respectively. For females heterozygous for class I-III G6PD variants, phenotype is variable due to X-linked mosaicism and thus an enzyme test is recommended prior to rasburicase use. An enzyme test to determine G6PD phenotype is also the recommendation for patients who have negative or inconclusive genetic results.

> View the CPIC guidelines for G6PD variants & rasburicase.

> Read the accepted article preview of the guideline manuscript:
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Rasburicase Therapy in the context of G6PD Deficiency Genotype.
Relling MV, McDonagh EM, Chang T, Caudle KE, McLeod HL, Haidar CE, Klein T, Luzzatto L.
Clin Pharmacol Ther. Accepted article preview online 02 May 2014 doi:10.1038/clpt.2014.97.

> Learn more about G6PD and drug response.

> Learn more about the mechanism underlying rasburicase-induced hemolytic anemia.