This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
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
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Colucci, P.
Right arrow Articles by Ducharme, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Colucci, P.
Right arrow Articles by Ducharme, M. P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2009, p. 662-669, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00907-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Multiple-Dose Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered over 21 Days with Lopinavir-Ritonavir in Human Immunodeficiency Virus Type 1-Infected Subjects {triangledown}

Philippe Colucci,1 John C. Pottage,2 Heather Robison,2 Jacques Turgeon,1 Dirk Schürmann,3 I. M. Hoepelman,4 and Murray P. Ducharme1,5*

Faculté de Pharmacie, University of Montreal, Montreal, Canada,1 Achillion Pharmaceuticals, Inc., New Haven, Connecticut,2 Charité-Universitätsmedizin Berlin, Berlin, Germany,3 University Medical Center, Utrecht, The Netherlands,4 Cetero Research, Cary, North Carolina5

Received 8 July 2008/ Accepted 8 November 2008

The purpose of this study was to describe the plasma pharmacokinetics (PK) of elvucitabine at different doses when administered daily or every other day for 21 days with lopinavir-ritonavir (Kaletra) in human immunodeficiency virus (HIV)-infected subjects. Three different dosing regimens of elvucitabine were administered with lopinavir-ritonavir to 24 subjects with moderate levels of HIV. Plasma samples were collected over 35 days. Elvucitabine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK of elvucitabine was determined using both noncompartmental and compartmental analyses. Models were developed and tested using ADAPT II, while a population analysis was performed using IT2S. The PK behavior of elvucitabine was best described by a two-compartment linear model using two absorption rates and an increase in the bioavailability after day 1. The augmentation in the bioavailability after day 1 was variable, with some subjects demonstrating a major increase while others had little or no increase. Elvucitabine has a long half-life of approximately 100 h. The increase in elvucitabine bioavailability may be due to ritonavir inhibiting an efflux gut transporter with activity present in various levels between subjects. The proposed PK model may be utilized and improved further by linking the PK behavior of elvucitabine to various markers of efficacy.

* Corresponding author. Mailing address: Cetero Research, 2000 Regency Parkway, Suite 295, Cary, NC 27518. Phone: (514) 463-4367. E-mail: murray.ducharme{at}cetero.com

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 662-669, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00907-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Colucci, P., Pottage, J. C., Robison, H., Turgeon, J., Ducharme, M. P. (2009). Effect of a Single Dose of Ritonavir on the Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered in Healthy Volunteers. Antimicrob. Agents Chemother. 53: 646-650 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»