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Clinical Trial
. 2004 Jan;48(1):124-9.
doi: 10.1128/AAC.48.1.124-129.2004.

Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children

Rohan Hazra  1 , Frank M Balis, Antonella N Tullio, Ellen DeCarlo, Carol J Worrell, Seth M Steinberg, John F Flaherty, Kitty Yale, Marianne Poblenz, Brian P Kearney, Lijie Zhong, Dion F Coakley, Stephane Blanche, Jean Louis Bresson, Judith A Zuckerman, Steven L Zeichner
Affiliations
Clinical Trial

Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children

Rohan Hazra et al. Antimicrob Agents Chemother. 2004 Jan.

Abstract

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/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) 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 AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) 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, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg.

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Figures

FIG. 1.
FIG. 1.
Diagram outlining the study schema.
FIG. 2.
FIG. 2.
Concentrations of tenofovir in serum after the first dose and at steady state. Data are the mean ± standard deviation for the subjects in the study.
See this image and copyright information in PMC

References

    1. Balis, F. M., P. A. Pizzo, K. M. Butler, M. E. Hawkins, P. Brouwers, R. N. Husson, F. Jacobsen, S. M. Blaney, J. Gress, P. Jarosinski, and D. G. Poplack. 1992. Clinical pharmacology of 2′,3′-dideoxyinosine in human immunodeficiency virus-infected children. J. Infect. Dis. 165:99-104. - PubMed
    1. Balzarini, J., A. Holy, J. Jindrich, L. Naesens, R. Snoeck, D. Schols, and E. De Clercq. 1993. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob. Agents Chemother. 37:332-338. - PMC - PubMed
    1. Barditch-Crovo, P., S. G. Deeks, A. Collier, S. Safrin, D. F. Coakley, M. Miller, B. P. Kearney, R. L. Coleman, P. D. Lamy, J. O. Kahn, I. McGowan, and P. S. Lietman. 2001. Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob. Agents Chemother. 45:2733-2739. - PMC - PubMed
    1. Deeks, S. G., P. Barditch-Crovo, P. S. Lietman, F. Hwang, K. C. Cundy, J. F. Rooney, N. S. Hellmann, S. Safrin, and J. O. Kahn. 1998. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults. Antimicrob. Agents Chemother. 42:2380-2384. - PMC - PubMed
    1. Fox, E., and F. M. Balis. 2001. Drug therapy in neonates and pediatric patients, p. 293-305. In A. J. Atkinson, Jr., C. E. Daniels, R. L. Dedrick, C. V. Grudzinskas, and S. P. Markey (ed.), Principles of clinical pharmacology. Academic Press, San Diego, Calif.

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