Monday, May 18, 2015

PharmGKB efavirenz pharmacokinetic pathway published in Pharmacogenetics and Genomics

The PharmGKB summary describing the efavirenz (EFV) pharmacokinetic pathway, and the pharmacogenetic variants that affect EFV pharmacokinetics has been published by Pharmacogenetics & Genomics

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor that is used as part of a highly active anti-retroviral therapy (ART) regimen (HAART) against HIV-1 infection. The primary route of EFV metabolism is through CYP2B6 to 8-hydroxyefavirenz (8-hydroxy-EFV).  In vitro studies using human liver microsomes show that there is considerable variability in the formation rate of 8-hydroxy-EFV between samples and genetic variants in CYP2B6 are likely major contributors to this variability. There is also evidence that CYP3A4, CYP3A5, CYP1A2 and CYP2A6 also play minor roles in this xenometabolic step. 

View the interactive online version of the PharmGKB summary: Efavirenz pathway, pharmacokinetics (PK) here and on Pubmed.

View all pathways on PharmGKB. 

Monday, May 11, 2015

New CPIC Guideline: CYP2D6 and CYP2C19 and Selective Serotonin Reuptake Inhibitors

Guidelines by the Clinical Pharmacogenetics Implementation Consortium (CPIC) regarding the use of pharmacogenetic tests for CYP2D6 and CYP2C19 in dosing selective serotonin reuptake inhibitors (SSRIs) have been accepted for publication in Clinical Pharmacology and Therapeutics.

SSRIs are used as a first line treatment for major depressive and anxiety disorders, and may be used to treat other psychiatric conditions. Paroxetine and fluvoxamine are extensively metabolized by CYP2D6 and variations in CYP2D6 activity may result in lower or greater exposure to these drugs. While variations in CYP2C19 activity may result in altered drug exposure for citalopram, escitalopram, and sertraline.

For therapeutic recommendations and further details see these guidelines for paroxetine, fluvoxamine, citalopram, escitalopram, and sertraline on PharmGKB.