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 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/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 (200 mg 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 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/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 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.

Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents / C., Königs; C., Feiterna Sperling; Esposito, Susanna Maria Roberta; C., Viscoli; R., Rosso; T. N., Kakuda; R., Leemans; M., Peeters; R., Mack; I., Peeters; R., Sinha; K., Boven; C., Giaquinto. - In: AIDS. - ISSN 0269-9370. - 26:4(2012), pp. 447-455. [10.1097/QAD.0b013e32834f30b1]

Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents

Esposito, Susanna Maria Roberta;
2012-01-01

Abstract

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 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/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 (200 mg 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 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/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 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
2012
Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents / C., Königs; C., Feiterna Sperling; Esposito, Susanna Maria Roberta; C., Viscoli; R., Rosso; T. N., Kakuda; R., Leemans; M., Peeters; R., Mack; I., Peeters; R., Sinha; K., Boven; C., Giaquinto. - In: AIDS. - ISSN 0269-9370. - 26:4(2012), pp. 447-455. [10.1097/QAD.0b013e32834f30b1]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2864447
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