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Antimicrobial Agents and Chemotherapy, February 2009, p. 646-650, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00905-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of a Single Dose of Ritonavir on the Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered in Healthy Volunteers{triangledown}

Philippe Colucci,1 John C. Pottage,2 Heather Robison,2 Jacques Turgeon,1 and Murray P. Ducharme1,3*

Faculté de Pharmacie, University of Montreal, Montreal, Canada,1 Achillion Pharmaceuticals, Inc., New Haven, Connecticut,2 Cetero Research, Cary, North Carolina3

Received 8 July 2008/ Accepted 8 November 2008

The purpose of this study was to determine the effect of a single dose of 300 mg of ritonavir on the plasma pharmacokinetics (PK) of a single dose of 20 mg of elvucitabine when the two drugs were coadministered in healthy subjects. In a three-way crossover design, 30 subjects received 20 mg of elvucitabine, 300 mg of ritonavir, or 20 mg of elvucitabine coadministered with 300 mg of ritonavir. 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. Comparisons of PK parameters between groups were done with SAS. The pharmacokinetic behavior of elvucitabine was best described by a two-compartment linear model using two absorption rates and a first-order elimination rate. Ritonavir significantly impacted the PK of elvucitabine by reducing elvucitabine's bioavailability, with the most plausible explanation being an inhibition on influx transporters by ritonavir. The decrease in elvucitabine bioavailability when elvucitabine was coadministered with ritonavir may be due to ritonavir's inhibiting influx gut transporters. Continued development of elvucitabine is warranted to better characterize its PK and to determine its in vivo efficacy against human immunodeficiency virus.

* 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. 646-650, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00905-08
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., Schurmann, D., Hoepelman, I. M., Ducharme, M. P. (2009). 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. Antimicrob. Agents Chemother. 53: 662-669 [Abstract] [Full Text]  


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