A Multi-gene Pharmacogenetic Panel to Prevent Adverse Drug Reactions in Daily Primary Care Practice: Open-label, Mayo Clinic Multisite (Mankato-Rochester Primary Care), Controlled, Implementation Study Taking the Results of the PREPARE Study Into Minnesota (PREPARE-Mayo)

The purpose of this study is to determine whether the implementation of pre-emptive pharmacogenomic (PGx) testing of a panel of clinically relevant PGx markers, to guide the dose and drug selection for 39 commonly prescribed drugs, will result in an overall reduction in the number of clinically relevant drug-genotype associated ADRs which are causally related to the initial drug of inclusion (referred to as 'index drug').

Start Date01 Nov 2024

Sponsor / Collaborator

Mayo Clinic

NCT05981573 / Enrolling by invitationNot Applicable

Assessment of Methadone Dose Taken Using Electrochemistry

Proof of concept: Pilot Study
A Pilot, proof of concept, observational study with a long-term goal to develop a minimally invasive wearable Remote Medication Monitor (RMM) that provides continuous, real-time data on methadone levels in interstitial fluid (ISF). An RMM could be used as a medication adherence monitor and would allow for the physician, counselor, patient, or family member to remotely verify that a physician-prescribed dose has been taken.

Start Date26 Aug 2024

Sponsor / Collaborator

CARI Health, Inc.

NCT06511401 / RecruitingNot ApplicableIIT

C-PAIN: Catalyzing Pharmacogenomic Analysis for Informing Pain Treatment

This is a randomized, prospective study to evaluate the effects of preemptive pharmacogenomic (PGx) testing on opioid dosing decisions/selections and pain score in cancer patients.

Start Date10 Jul 2024

Sponsor / Collaborator

The University of Chicago

[+1]

100 Clinical Results associated with Drug Metabolism, Poor, CYP2D6-Related

100 Translational Medicine associated with Drug Metabolism, Poor, CYP2D6-Related

0 Patents (Medical) associated with Drug Metabolism, Poor, CYP2D6-Related

Literatures (Medical) associated with Drug Metabolism, Poor, CYP2D6-Related

01 Jun 2024·Acta Gastro Enterologica Belgica

CYP2D6 polymorphism may contribute to Trazodone-induced hepatotoxicity: a rare case of drug-drug-gene induced liver injury

Article

Author: Missiaen, L ; Declerck, L ; Seynhaeve, L ; Melis, C ; Ferdinande, K ; Decaestecker, J ; De Vloo, C

A 46-year-old female with a history of type I diabetes, alopecia areata and autoimmune hypothyroidism presented with a significant hepatocellular hepatitis. The top 3 differential diagnoses were drug-induced liver injury, autoimmune hepatitis and drug-induced autoimmune hepatitis. Considering the predisposition for immune-mediated conditions, we performed a liver biopsy to exclude an autoimmune hepatitis. A temporal relationship between the onset of liver injury and the start of Trazodone and Escitalopram was observed. We report a case of Trazodone-induced liver injury in which pharmacogenomic testing identified a CYP2D6 gene polymorphism leading to CYP2D6 dysfunction and accumulation of Trazodone’s potential hepatotoxic metabolite m-CPP, which elucidates the underlying pathogenesis. This case also presents an example of a drug-drug-gene interaction between Trazodone and the not-so-innocent bystander Escitalopram leading to an additional component of CYP2D6 inhibition. This case highlights the potential benefit of targeted pharma-cogenomic testing to minimise the risk of drug-induced liver injury.

01 Dec 2022·Clinical Pharmacology & Therapeutics

Physiologically‐Based Pharmacokinetic Model Development, Validation, and Application for Prediction of Eliglustat Drug–Drug Interactions

Article

Author: Al‐Kofahi, Mahmoud ; Jarnes, Jeanine R. ; Cheng, Shen ; Weinreb, Neal J. ; Kartha, Reena V. ; Sahasrabudhe, Siddhee A.

Eliglustat is a glucosylceramide synthase inhibitor indicated as a long‐term substrate reduction therapy for adults with type 1 Gaucher disease, a lysosomal rare disease. It is primarily metabolized by cytochrome P450 2D6 (CYP2D6), and variants in the gene encoding this enzyme are important determinants of eliglustat pharmacokinetics (PK) and drug–drug interactions (DDIs). The existing drug label addresses the DDIs to some extent but has omitted scenarios where both metabolizing CYPs (2D6 and 3A4) are mildly or moderately inhibited. The objectives of this study were (i) to develop and validate an eliglustat physiologically‐based pharmacokinetic (PBPK) model with and without drug interactions, (ii) to simulate untested DDI scenarios, and (iii) to explore potential dosing flexibility using lower dose strength of eliglustat (commercially not available). PK data from healthy adults receiving eliglustat with or without interacting drugs were obtained from literature and used for the PBPK model development and validation. The model‐predicted single‐dose and steady‐state maximum concentration (Cmax) and area under the concentration‐time curve (AUC) of eliglustat were within 50–150% of the observed values when eliglustat was administered alone or coadministered with ketoconazole or paroxetine. Then as model‐based simulations, we illustrated eliglustat exposure as a victim of interaction when coadministered with fluvoxamine following the US Food and Drug Administration (FDA) dosing recommendations. Second, we showed that with lower eliglustat doses (21 mg, 42 mg once daily) the exposure in participants of intermediate and poor metabolizer phenotypes was within the outlined safety margin (Cmax <250 ng/mL) when eliglustat was administered with ketoconazole, where the current recommendation is a contraindication of coadministration (84 mg). The present study demonstrated that patients with CYP2D6 deficiency may benefit from lower doses of eliglustat.

02 Sep 2019·Clinical ToxicologyQ3 · MEDICINE

Delayed resolution of amitriptyline toxicity secondary to CYP2D6 deficiency

Q3 · MEDICINE

Letter

Author: Greenberg, Michael I. ; Khalid, Muhammad Masood ; Dela Cruz, Maricel ; Vearrier, David

Dear Editor,A 44-year-old female presented to the emergency department after taking 4.5 g of amitriptyline in a suicide attempt. On presentation, the patient was alert and oriented with normal vita...

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