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Antimicrobial Agents and Chemotherapy, January 2004, p. 124-129, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.124-129.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Single-Dose and Steady-State Pharmacokinetics of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Children

Rohan Hazra,1 Frank M. Balis,2 Antonella N. Tullio,1 Ellen DeCarlo,1 Carol J. Worrell,1 Seth M. Steinberg,3 John F. Flaherty,4 Kitty Yale,4 Marianne Poblenz,4 Brian P. Kearney,4 Lijie Zhong,4 Dion F. Coakley,4 Stephane Blanche,5 Jean Louis Bresson,5 Judith A. Zuckerman,1 and Steven L. Zeichner1*

HIV and AIDS Malignancy Branch,1 Pediatric Oncology Branch,2 Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland,3 Gilead Sciences, Foster City, California,4 Hopital Necker Enfants Malades, Paris, France5

Received 23 May 2003/ Returned for modification 21 July 2003/ Accepted 23 September 2003

Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m2; the median administered dose was 208 mg/m2. Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to {infty} (AUC0-{infty}) was 2,150 ng · h/ml and the geometric mean maximum concentration (Cmax) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng · h/ml and was significantly higher than the AUC0-{infty} after the first dose (P = 0.0004). The geometric mean Cmax at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, ~3,000 ng · h/ml; Cmax, ~300 ng/ml) treated with tenofovir DF at 300 mg.

* Corresponding author. Mailing address: Building 10, Room 10S255, MSC 1868, Bethesda, MD 20892-1868. Phone: (301) 402-3637. Fax: (301) 480-8250. E-mail: zeichner{at}nih.gov.

Antimicrobial Agents and Chemotherapy, January 2004, p. 124-129, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.124-129.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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