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Antimicrobial Agents and Chemotherapy, March 2004, p. 918-923, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.918-923.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of Indinavir and Nelfinavir in Treatment-Naive, Human Immunodeficiency Virus-Infected Subjects

Robert DiCenzo,1 Alan Forrest,1 Margaret A. Fischl,2 Ann Collier,3 Judith Feinberg,4 Heather Ribaudo,5 Robin DiFrancecso,1 Gene D. Morse,1* and the AIDS Clinical Trials Group 388/733/5060 Study Team{dagger}

University at Buffalo, Buffalo, New York,1 University of Miami, Miami, Florida,2 University of Washington, Seattle, Washington,3 University of Cincinnati, Cincinnati, Ohio,4 Harvard University, Boston, Massachusetts5

Received 22 July 2003/ Returned for modification 23 September 2003/ Accepted 4 November 2003

AIDS Clinical Trials Group protocol 388 was designed to compare a three-drug regimen (indinavir with dual nucleosides) to a four-drug regimen (indinavir plus nelfinavir or indinavir plus efavirenz with dual nucleosides). Blood samples from patients taking indinavir and nelfinavir were collected over 8 to 12 h following a specified dose and were analyzed with high-performance liquid chromatography. Pharmacokinetic data were derived by using noncompartmental analysis. Following administration of indinavir every 8 h in the absence of nelfinavir (n = 8), the median predose indinavir concentration (C0) was 369 ng/ml (range, <10 to 949 ng/ml; one subject had a concentration of <10 ng/ml), and the concentration 8 h after administration of the study dose was 159 ng/ml (range, 85 to 506 ng/ml). In the group receiving 1,000 mg of indinavir every 12 h with nelfinavir (n = 10), the median indinavir C0 was <10 ng/ml (range, <10 to 3,740 ng/ml; six subjects had a value of <10 ng/ml), and the C12 h was 44 ng/ml (range, <10 to 4,236 ng/ml; five subjects had a value of <10 ng/ml), while the subjects who received 1,200 mg of indinavir every 12 h with nelfinavir (n = 7) had a C0 of 146 ng/ml (range, 58 to 5,215 ng/ml) and a C12 h of 95 ng/ml (range, 12 to 954 ng/ml). Indinavir clearance was significantly lower in the presence of nelfinavir (median [interquartile range], 34.1 liters/h [range, 22.6 to 45.8 liters/h] versus 47.9 liters/h [range, 42.7 to 70.3 liters/h]; P < 0.017). For subjects receiving 1,000 mg of indinavir every 12 h, the median C0 value for nelfinavir (n = 9) was 1,779 ng/ml (range, <187.5 to 4,579 ng/ml), and the C12 h was 1,554 ng/ml (range, <187.5 to 5,540 ng/ml). Due to the unacceptable number of undetectable indinavir trough concentrations, 1,200 mg of indinavir appears to be the preferred dose in a twice-daily regimen that includes nelfinavir.

* Corresponding author. Mailing address: AACTG Pharmacology Support Laboratory, 317 Hochstetter Hall, University at Buffalo, Amherst, NY 14260. Phone: (716) 645-2828, ext. 252. Fax: (716) 645-2001. E-mail: emorse{at}acsu.buffalo.edu.

{dagger} Contributing members of the ACTG 388/733/5060 Study Team are listed in Acknowledgments.

Antimicrobial Agents and Chemotherapy, March 2004, p. 918-923, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.918-923.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Smith, P. F., Robbins, G. K., Shafer, R. W., Wu, H., Yu, S., Hirsch, M. S., Merigan, T. C., Park, J.-G., Forrest, A., Fischl, M. A., Morse, G. D., the ACTG 384-5006 Team, (2005). Pharmacokinetics of Nelfinavir and Efavirenz in Antiretroviral-Naive, Human Immunodeficiency Virus-Infected Subjects when Administered Alone or in Combination with Nucleoside Analog Reverse Transcriptase Inhibitors. Antimicrob. Agents Chemother. 49: 3558-3561 [Abstract] [Full Text]  


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