DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on October 11, 2006; DOI: 10.1124/dmd.106.011973

0090-9556/07/3501-180-184$20.00
DMD 35:180-184, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.106.011973v1
35/1/180    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Krishnan, S.
Right arrow Articles by Moncrief, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Krishnan, S.
Right arrow Articles by Moncrief, S.

An Evaluation of the Cytochrome P450 Inhibition Potential of Lisdexamfetamine in Human Liver Microsomes

Suma Krishnan, and Scott Moncrief

New River Pharmaceuticals, Blacksburg, Virginia

The human cytochrome P450 (P450) system is implicated in many drug interactions. Lisdexamfetamine dimesylate (NRP104), the proposed generic name for a new agent under investigation for treatment of attention deficit hyperactivity disorder, was recently analyzed for inhibitory drug-drug interactions with seven major P450 isoforms using pooled human liver microsomes. Probe substrates were used near the Km concentration values reported in the literature for CYP1A2 (phenacetin), CYP2A6 (coumarin), CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2C19 ([S]-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam and testosterone), and lisdexamfetamine was evaluated at concentrations ranging from 0.01 to 100 µM for its ability to inhibit the activity of these seven P450 isoforms. NADPH was added to one set of samples to initiate metabolic reactions, which were then terminated by adding organic solvent, vortexing the samples, and placing them on ice. The relevant substrates were then introduced to both sets of samples so that the percentage of remaining activity could be measured and compared. In addition, these samples were compared with other samples with the same concentrations of lisdexamfetamine but without preincubation. None of the seven P450 isoforms showed any concentration-dependent inhibition. Comparison of results from microsomes preincubated with and without NADPH showed no mechanism-based inhibition. Neither concentration-dependent nor mechanism-based inhibition caused by time-dependent inactivation of human P450 isoforms was shown for lisdexamfetamine during in vitro testing. The evidence suggests that lisdexamfetamine has a low potential for drug-drug interactions or initiation of drug-drug interactions.

Address correspondence to: Suma Krishnan, 2200 Kraft Drive, Suite 2050, Blacksburg, VA 24060. E-mail: skrishnan{at}nrpharma.com




This article has been cited by other articles:


Home page
 Am J Health Syst PharmHome page
B. Popovic, P. Bhattacharya, and L. Sivaswamy
Lisdexamfetamine: A prodrug for the treatment of attention-deficit/hyperactivity disorder
Am. J. Health Syst. Pharm., November 15, 2009; 66(22): 2005 - 2012.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
B. J Cowles
Lisdexamfetamine for Treatment of Attention-Deficit/Hyperactivity Disorder
Ann. Pharmacother., April 1, 2009; 43(4): 669 - 676.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.