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Antimicrobial Agents and Chemotherapy, December 2001, p. 3663-3668, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3663-3668.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir

Brian M. Sadler,1,dagger Catherine Gillotin,2 Yu Lou,1 Joseph J. Eron,3 William Lang,4 Richard Haubrich,5 and Daniel S. Stein1,3,*

Glaxo Wellcome (now GlaxoSmithKline) Inc., Research Triangle Park,1 and University of North Carolina at Chapel Hill, Chapel Hill,3 North Carolina; Laboratoire Glaxo Wellcome, 781 Marly-le-Roi, France2; and ViRx Inc., San Francisco,4 and University of California, San Diego,5 California

Received 12 March 2001/Returned for modification 19 August 2001/Accepted 16 September 2001

In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUCss] and 37% for peak plasma concentration at steady state [Cmax,ss]) and increased by indinavir (33% for AUCss). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUCss or Cmax,ss. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

* Corresponding author. Mailing address: Clinical Pharmacology, GlaxoSmithKline Inc., Research Triangle Park, NC 27709-3398. Phone: (919) 483-5927. Fax: (919) 483-6380. E-mail: dss94020{at}gsk.com.

dagger Present address: Pharsite Corp., Cary, N.C.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3663-3668, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3663-3668.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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