Article

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

HIV and AIDS Malignancy Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 02/2004; 48(1):124-9. DOI: 10.1128/AAC.48.1.124-129.2004
Source: PubMed

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/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 ∞ (AUC0-∞) 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-∞ 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.

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