J Clin Pharmacol
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First published on April 15, 2009, doi:10.1177/0091270009335002

The Journal of Clinical Pharmacology 2009;49:661.

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©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270009335002

Article

Effect of Dietary Purines on the Pharmacokinetics of Orally Administered Ribavirin

Linghui Li 1*, Seok Hwee Koo 1, Lie Michael George Limenta 1, Li Han 2, Khadijah Binte Hashim 2, Hung Hiang Quek 2, and Edmund Jon Deoon Lee 1

1 National Univeristy of Singapore
2 Temasek Polytechnic

* To whom correspondence should be addressed. E-mail: g0403078{at}nus.edu.sg.


  Abstract
Ribavirin is found to be absorbed in the intestine through the human concentrative nucleoside transporter 2 (hCNT2). Cellular uptake of ribavirin was strongly inhibited by purine nucleoside in an in vitro study. This study aims to examine the effects of dietary purine on the pharmacokinetics of orally administered ribavirin in vivo. Twenty healthy participants were enrolled in a randomized, 2-period crossover study. Participants were administered a single 600-mg oral dose of ribavirin after either a high-purine meal or a low-purine meal. Serial blood samples were collected predose and over 144 hours after dosing. Ribavirin concentrations were measured by liquid chromatography/tandem mass spectrometry. In comparison with corresponding plasmavalues of ribavirin following a high-purine meal, Cmax, and AUC0-144 AUC0-{infty} of ribavirin following a low-purine meal were 136% (90% confidence internal [CI]: 120%155%), 134% (90% CI: 118%-153%), and 139% (90% CI: 120%-159%), respectively. This study indicates that dietary purines have an effect on ribavirin absorption. Dosage regimens of ribavirin might need to be adjusted according to the purine content of the meal.
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