Tenofovir pharmacokinetics in three tenofovir-containing regimens in children and adolescents
Polly Clayden, HIV i-Base
J King and coworkers reported pharmacokinetc (PK) parameters of tenofovir (TDF) tablets received in combination with efavirenz (EFV) or duranavir/ritonavir (DRV/r) or atazanavir/ritonavir (ATV/r) in a group of children and adolescents age 8-18 years.
This study enrolled patients receiving >=2 weeks TDF 300mg in combination with:
Arm 1: EFV 300mg or 600mg once-daily
Arm 2: DRV/ritonavir dosed at 300/100 or 600/100 twice-daily
Arm 3: ATV/ritonavir dosed at 200-400mg/100mg twice-daily
Plasma samples were taken at 0, 1, 2, 4, 6, 8, 12 and 24 hours post dose and plasma concentrations of TDF were measured.
The investigators performed statistical tests to evaluate whether the 90% confidence intervals of the geometric mean (GM) for the PK parameters of TDF were within the target range ie 0.5-2.0 fold of adult values: 2.8 (2.3-3.6) mgxh/L and 0.06 (0.05-0.08) mg/L AUC and Cmin respectively.
They found that among patients receiving EFV (n=15) the TDF GM (90% CI) AUC and Cmin were 2.9 (2.4-3.4) mg.h/L and 0.07 (0.05-0.09) mg/L respectively. AUC and Cmin were 3.1(2.4-4.0) mg.h/L and 0.07 (0.05-0.09) mg/L in patients receiving DRV/r (n=10) and 3.6 (3.0-4.5) mg.h/L and 0.07 (0.06-0.10) mg/L respectively in patients receiving ATZ/r (n=17).
They noted that the TDF Cmin 90% CI included values above the target upper limit of 0.08 mg/L in all three arms and the AUC 90% CI included values above the upper target limit of 3.6 mg.h/L in patients receiving DRV/r or ATV/r.
The investigators concluded: “These data suggest that DRV/r and ATV/r may increase TDF exposure in HIV-infected children and adolescents.”
King J et al. A comparison of tenofovir pharmacokinetics across three tenofovir-based antiretroviral regimens in HIV-infected children and adolescents. 10th International Workshop on Clinical Pharmacology of HIV Therapy, 15-17 April 2009, Amsterdam. Abstract P_53