title: Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.
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.
authors.affiliation: HIV and AIDS Malignancy Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Frank M
authors.initials: FM
authors.lastname: Balis
authors.forename: Antonella N
authors.initials: AN
authors.lastname: Tullio
authors.forename: Ellen
authors.initials: E
authors.lastname: DeCarlo
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Worrell
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.forename: Kitty
authors.initials: K
authors.lastname: Yale
authors.forename: Marianne
authors.initials: M
authors.lastname: Poblenz
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Dion F
authors.initials: DF
authors.lastname: Coakley
authors.forename: Stephane
authors.initials: S
authors.lastname: Blanche
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Bresson
authors.forename: Judith A
authors.initials: JA
authors.lastname: Zuckerman
authors.forename: Steven L
authors.initials: SL
authors.lastname: Zeichner
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine