Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 2
Abstract
Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug–drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and β-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.
Authors and Affiliations
Ai-Ming Yu
Keywords
Related Articles
- EP ID EP681545
- DOI 10.1208/s12248-008-9028-5
- Views 102
- Downloads 0
Multidrug Resistance Proteins (MRPs) and Cancer Therapy
The ATP-binding cassette (ABC) transporters are members of a protein superfamily that are known to translocate various substrates across membranes, including metabolic products, lipids and sterols, and xenobiotic drugs....
Target-Mediated Disposition Model Describing the Dynamics of IL12 and IFNγ after Administration of a Mifepristone-Inducible Adenoviral Vector for IL-12 Expression in Mice
The online version of this article (doi:10.1208/s12248-012-9423-9) contains supplementary material, which is available to authorized users.
An experimental approach for investigating consumers evaluation of pharmacist consultation services
The goal of this study was to investigate factors that influence consumers’ perceptions of service encounter satisfaction, overall service quality, and trust in the service provider for pharmacist consultation se...
AAPS–FIP Summary Workshop Report: Pharmacogenetics in Individualized Medicine: Methods, Regulatory, and Clinical Applications
The workshop “Pharmacogenetics in Individualized Medicine: Methods, Regulatory, and Clinical Applications” was held November 15–16, 2008 in Atlanta, Georgia, USA. This workshop provided an opportu...
In vitro–In Vivo Correlations: Tricks and Traps
In vitro–in vivo correlation (IVIVC) is a biopharmaceutical tool recommended to be used in development of formulation. When validated, it can speed up development of formulation, be used to fix dissolution limits...