Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.
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.
Hazra
Rohan
R
HIV and AIDS Malignancy Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland, USA.
Balis
Frank M
FM
Tullio
Antonella N
AN
DeCarlo
Ellen
E
Worrell
Carol J
CJ
Steinberg
Seth M
SM
Flaherty
John F
JF
Yale
Kitty
K
Poblenz
Marianne
M
Kearney
Brian P
BP
Zhong
Lijie
L
Coakley
Dion F
DF
Blanche
Stephane
S
Bresson
Jean Louis
JL
Zuckerman
Judith A
JA
Zeichner
Steven L
SL
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008297:Male; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068698:Tenofovir
D019380:Anti-HIV Agents; D004338:Drug Combinations; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine