Journal of Pharmacology And Experimental Therapeutics Fast Forward

[Snowy Owl]

Re: Journal of Pharmacology And Experimental Therapeutics Fast Forward

Sorry LMonty my forgoy.

I have inserted the linl in the original post.

http://jpet.aspetjournals.org/cgi/content/abstract/jpet.106.111807v1

[sharon sanders]

Clopidogrel

Description of:

http://www.nlm.nih.gov/medlineplus/d...di/203403.html

[LMonty]

Re: Journal of Pharmacology And Experimental Therapeutics Fast Forward

Snowy, do you have a link or date for this? I want to share it with the pharmacists at work...I'd need the reference for them.

Thanks!

[Mingus]

Re: Journal of Pharmacology And Experimental Therapeutics Fast Forward

This is of premium importance. ( bump! )

[Snowy Owl]

Journal of Pharmacology And Experimental Therapeutics Fast Forward
ANTI-INFLUENZA VIRAL PRODRUG OSELTAMIVIR IS ACTIVATED BY CARBOXYLESTERASE HCE1 AND THE ACTIVATION IS INHIBITED BY ANTI-PLATELET AGENT CLOPIDOGREL

<nobr>Deshi Shi ¹,</nobr> <nobr>Jian Yang ¹,</nobr> <nobr>Dongfang Yang ¹,</nobr> <nobr>Edward L LeCluyse ²,</nobr> <nobr>Chris Black ²,</nobr> <nobr>Li You ¹,</nobr> <nobr>Fatemeh Akhlaghi ¹,</nobr> <nobr>Bingfang Yan ¹^*</nobr>

University of Rhode Island ² CellDirect

http://jpet.aspetjournals.org/cgi/content/abstract/jpet.106.111807v1

Abstract

Oseltamivir is the main medicine recommended by the World HealthOrganization in anticipation of next influenza pandemic. Thisanti-influenza viral agent is an ester prodrug and the anti-viralactivity is achieved by its hydrolytic metabolite: oseltamivircarboxylate.

In this study, we report that the hydrolytic activationis catalyzed by carboxylesterase HCE1. Liver microsomes rapidlyhydrolyzed oseltamivir, but no hydrolysis was detected withintestinal microsomes or plasma.

The overall rate of the hydrolysisvaried among individual liver samples and was correlated wellwith the level of HCE1. Recombinant HCE1 but not HCE2 hydrolyzedthis prodrug and produced similar kinetic parameters as theliver microsomes. Several HCE1 natural variants differed fromthe wild type enzyme on the hydrolysis of oseltamivir.

In thepresence of anti-platelet agent clopidogrel, the hydrolysisof oseltamivir was inhibited by as much as 90% when the equalconcentration was assayed.

Given the fact that hydrolysis ofoseltamivir is required for its therapeutic activity, concurrentuse of both drugs would inhibit the activation of oseltamivir,thus making this anti-viral agent therapeutically inactive.

This is epidemiologically of significance, because people whoreceive oseltamivir and clopidogrel simultaneously may maintainsusceptibility to influenza infection or a source of spreadinginfluenza virus if already infected.