Single-Dose and Steady-State Pharmacokinetics of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Children
AUTOR(ES)
Hazra, Rohan
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=310184Documentos Relacionados
- Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.
- Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients.
- Single-dose and steady-state pharmacokinetics of a novel microfluidized suspension of atovaquone in human immunodeficiency virus-seropositive patients.
- Phase I/II Trial of the Pharmacokinetics, Safety, and Antiretroviral Activity of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Adults
- Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Infected Patients with End-Stage Renal Disease Receiving Chronic Dialysis