TY - JOUR
T1 - Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents
AU - Königs, Christoph
AU - Feiterna-Sperling, Cornelia
AU - Esposito, Susanna
AU - Viscoli, Claudio
AU - Rosso, Raffaella
AU - Kakuda, Thomas N.
AU - Leemans, Ruud
AU - Peeters, Monika
AU - MacK, Rebecca
AU - Peeters, Ingeborg
AU - Sinha, Rekha
AU - Boven, Katia
AU - Giaquinto, Carlo
PY - 2012/2/20
Y1 - 2012/2/20
N2 - Objectives: To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents. Design: Phase I, nonrandomized, open-label study in two stages. Methods: Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50copies/ml were enrolled. In both stages, etravirine (4mg/kg twice daily in stage I, 5.2mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200mg twice daily) combination antiretroviral regimen. Results: Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757ng/ml (680), respectively; area under the plasma concentration-time curve over 12h was 4050 (3602) and 6141ngh/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses. CONCLUSION:: Etravirine 5.2mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
AB - Objectives: To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents. Design: Phase I, nonrandomized, open-label study in two stages. Methods: Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50copies/ml were enrolled. In both stages, etravirine (4mg/kg twice daily in stage I, 5.2mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200mg twice daily) combination antiretroviral regimen. Results: Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757ng/ml (680), respectively; area under the plasma concentration-time curve over 12h was 4050 (3602) and 6141ngh/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses. CONCLUSION:: Etravirine 5.2mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
KW - children
KW - etravirine
KW - HIV-1
KW - pediatric
KW - pharmacokinetics
KW - phase I
UR - http://www.scopus.com/inward/record.url?scp=84857037886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857037886&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e32834f30b1
DO - 10.1097/QAD.0b013e32834f30b1
M3 - Article
C2 - 22156961
AN - SCOPUS:84857037886
VL - 26
SP - 447
EP - 455
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 4
ER -