Wednesday, January 20, 2021

CYP2B6 GeneFocus paper published

The latest paper in the PharmVar GeneFocus series, looking at CYP2B6, has now been published in Clinical Pharmacology and Therapeutics.

CYP2B6 is the only member of the CYP2B subfamily to encode a functional enzyme. Variation in this gene impacts the metabolism of several clinically important drugs, including efavirenz (see the CPIC guideline and annotation on PharmGKB), methadone and bupropion. 

The paper gives an overview of CYP2B6 genetic variation and outlines the gene’s previous nomenclature system prior to being catalogued by PharmVar. Details of CYP2B6 resources on PharmGKB and CPIC as well as reference materials for genetic testing are also provided.

CYP2B6 has now been curated into PharmVar, with some alleles revised to remove SNPs with little or no evidence available to show that they caused a change in CYP2B6 function. Users should also note that the *16 and *18 alleles have been consolidated, with *16 now listed as a suballele of *18. All changes have been recorded and can be found on the PharmVar page for CYP2B6.  PharmGKB and CPIC will be updating CYP2B6 information accordingly.

PharmVar would like to thank all members of the CYP2B6 gene expert panel for their efforts in curating this important gene.

Thursday, January 14, 2021

CPIC opioids guideline now annotated on PharmGKB

The CPIC guideline for opioid therapy and CYP2D6, OPRM1 and COMT was recently published in Clinical Pharmacology and Therapeutics and has now been annotated on PharmGKB. This guideline is an update to the CPIC guideline for codeine and CYP2D6, but now includes information on two other genes, OPRM1 and COMT, and a number of other opioids.

The guideline gives specific dosing recommendations for CYP2D6 and three drugs; codeine, tramadol and hydrocodone. Codeine and tramadol are not recommended for CYP2D6 ultrarapid metabolizers due to an increased risk of toxicity, nor for CYP2D6 poor metabolizers, where there is a risk of insufficient analgesia. The authors also recommend that CYP2D6 intermediate and poor metabolizers be monitored for analgesic response following the initiation of hydrocodone therapy. If patients with either of these metabolizer phenotypes fail to have an analgesic response to hydrocodone, a non-codeine or non-tramadol opioid can be considered.

Studies looking at the effects of variants in OPRM1 and COMT on opioid response were also assessed as part of this guideline update. OPRM1 encodes the mu opioid receptor, which binds to many opioids, while COMT codes for the enzyme Catechol-O-methyltransferase. COMT methlyates catecholamines and is thought to regulate pain perception. Due to the low quantity and/or quality of available evidence, the authors specifically issued no recommendations for opioid dosing based on OPRM1 or COMT variants. This is an important feature of the guideline, as testing for variants in these two genes in relation to opioid response is included in some pharmacogenomic tests.

In order to fully capture the size and complexity of this guideline, it is covered by multiple guideline annotations on PharmGKB, including extended dosing guidelines with genotype pickers for codeine, tramadol and hydrocodone. All guideline annotations can be accessed via the PharmGKB Clinical Guideline Annotations page. The full guideline manuscript, supplement and relevant implementation resources are also freely available on the CPIC website.

Thursday, January 7, 2021

New PharmGKB pathway for Cannabidiol Pharmacokinetics

PharmGKB released a new pharmacokinetics pathway for Cannabidiol, a phytocannabionoid found in the Cannabis sativa plant approved to treat two rare forms of epilepsy. 

The pathway was produced by graduate student Kris Oreschak from the University of Colorado Denver Anschutz Medical Campus with guidance from scientific curator Dr Caroline F. Thorn. While there are currently no published studies documenting the pharmacogenomics of cannabidiol, many pharmacogenes are involved in its metabolism presenting future opportunities to look at variable responses. 

View all pathways at PharmGKB