Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants

Title Page Differences in methadone metabolism by CYP2B6 variants

Abstract Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. Cytochrome P4502B6 (CYP2B6) mediates clinical methadone clearance and metabolic inactivation via N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Retrospective studies suggest that individuals with the CYP2B6*6 allelic variant have higher methadone plasma concentrations. Catalytic activities of CYP2B6 variants are highly substrate-and expression-system dependent. This investigation evaluated methadone N-demethylation by expressed human CYP2B6 allelic variants in an insect cell co-expression system containing P450 reductase. Additionally, the influence of co-expressing cytochrome b 5 , whose role in metabolism can be inhibitory or stimulatory, and dependent on the CYP isoform and substrate, on methadone metabolism was evaluated

Two novel biomarkers for early diagnosis of renal cell carcinoma [abstract]

Urinary aquaporin-I (AQP-1) and adipose differentiation-related protein (ADFP) as biomarkers of kidney cancer. This is a new process, applicable to humans, for 1) early and noninvasive detection of renal cancer, 2) population screening for renal cancer, 3) post-treatment surveillance for recurrence of renal cancer, 4) progression, regression or time-course of disease in untreated, partially treated, and definitively treated patients with renal cancer. The process is noninvasive, using readily available biological fluids such as urine and possibly blood. The proteins AQP-2 and ADFP are over-expressed in renal cancer tissue. These proteins may be shed into urine. The invention, per se, is a method (Western blot analysis or ELISA) for the sensitive detection and quantification of AQP-2 and ADFP in human urine, a readily available biological fluid, and the application of this assay for the detection and diagnosis of renal cancer, population screening for kidney cancer, surveillance for recurrence following or during treatment, and determining success of treatment and assessment of prognosis. Potential Areas of Applications: * Oncology * Markers Patent Status: Pending Inventor(s): Evan Kharasch, MD, PhD Contact Info: Jon Kratochvil, Esq. [email protected] (314) 747-092