J Clin Pharmacol
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0091270009335002v1
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PHARMACOKINETICS

Effect of Dietary Purines on the Pharmacokinetics of Orally Administered Ribavirin

Linghui Li, MD, Seok Hwee Koo, PhD, Lie Michael George Limenta, PhD, Li Han, MSc, Khadijah Binte Hashim, Hung Hiang Quek, PhD and Edmund Jon Deoon Lee, MD, PhD

From the Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Dr Li, Dr Koo, Dr Limenta, Dr Lee) and Temasek Applied Science School, Temasek Polytechnic, Republic of Singapore (Dr Han, Dr Hashim, Dr Quek).

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 plasma values of ribavirin following a high-purine meal, Cmax, AUC0-144 and 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.

Key Words: Ribavirin • pharmacokinetics • dietary purine • hCNT2

Address for reprints: Edmund Jon Deoon Lee, Department of Pharmacology, National University of Singapore, Clinical Research Centre, Blk MD11, #05-9, 10 Medical Drive, Singapore 117597; e-mail: edlee{at}nus.edu.sg.


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