دورية أكاديمية
أعرض في EDS

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Relationships of Etravirine in HIV-1-Infected, Treatment-Experienced Children and Adolescents in PIANO.

التفاصيل البيبلوغرافية
العنوان: Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Relationships of Etravirine in HIV-1-Infected, Treatment-Experienced Children and Adolescents in PIANO.
المؤلفون: Kakuda TN; Janssen Research & Development LLC, Titusville, NJ, USA. tkakuda@its.jnj.com., Brochot A; Janssen Research & Development, Beerse, Belgium., Green B; Model Answers Pty Ltd, Brisbane, Australia., Nijs S; Janssen Infectious Diseases BVBA, Beerse, Belgium., Vis P; LAP&P Consultants BV, Leiden, The Netherlands., Opsomer M; Janssen Infectious Diseases BVBA, Beerse, Belgium., Tomaka FL; Janssen Research & Development LLC, Titusville, NJ, USA., Hoetelmans RM; Janssen Infectious Diseases BVBA, Beerse, Belgium.
المصدر: Journal of clinical pharmacology [J Clin Pharmacol] 2016 Nov; Vol. 56 (11), pp. 1395-1405.
نوع المنشور: Clinical Trial, Phase II; Journal Article; Multicenter Study
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: England NLM ID: 0366372 Publication Model: Print Cited Medium: Internet ISSN: 1552-4604 (Electronic) Linking ISSN: 00912700 NLM ISO Abbreviation: J Clin Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2013- : Oxford : Wiley
Original Publication: Stamford, Conn., Hall Associates.
مواضيع طبية MeSH: HIV Infections/*blood , HIV-1/*drug effects , Pyridazines/*administration & dosage , Pyridazines/*blood , Reverse Transcriptase Inhibitors/*administration & dosage , Reverse Transcriptase Inhibitors/*blood, Adolescent ; Adult ; Child ; Drug Administration Schedule ; Female ; HIV Infections/drug therapy ; HIV Protease Inhibitors/administration & dosage ; HIV Protease Inhibitors/blood ; HIV Protease Inhibitors/pharmacokinetics ; Humans ; Male ; Nitriles ; Pyridazines/pharmacokinetics ; Pyrimidines ; Reverse Transcriptase Inhibitors/pharmacokinetics ; Treatment Outcome
مستخلص: PIANO (NCT00665847) investigated etravirine pharmacokinetics, efficacy, and safety in children and adolescents. Treatment-experienced, HIV-1-infected patients (≥6 to <18 years) received etravirine 5.2 mg/kg twice daily (maximum 200 mg twice daily) plus background antiretrovirals. A population pharmacokinetic model was developed, and etravirine C 0h and AUC 0-12h were estimated. Relationships among intrinsic/extrinsic factors and etravirine pharmacokinetics and pharmacokinetics with pharmacodynamics were assessed. The best model describing etravirine pharmacokinetics consisted of a single compartment with sequential zero- and first-order absorption following a lag time. Interindividual variability terms were included on clearance (CL/F) and the first-order input rate constant (KA). The final model estimates (coefficient of variation, %) for CL/F and KA were 46.3 (11) L/h and 1.07 (34) h -1 , respectively. Overall, median (range) estimated etravirine C 0h and AUC 0-12h were 287 (2-2276) ng/mL and 4560 (62-28,865) ng · h/mL, respectively. Exposure was slightly lower in adolescents vs children. Sex and adherence did not affect etravirine pharmacokinetics. Factors significantly affecting etravirine exposure were body weight (higher with lower weight), race (lower in Asians than in white or black patients), and the use of certain HIV protease inhibitors. Virologic response (<50 copies/mL at week 48) was lower in the lowest etravirine AUC 0-12h quartile vs the upper 3 quartiles (41% vs 67% to 76%). Rash occurred more frequently in the highest quartile than in the lower 3 quartiles (52% versus 8% to 20%). Etravirine 5.2 mg/kg twice daily in treatment-experienced, HIV-1-infected children and adolescents provides comparable exposure to that in adults receiving etravirine 200 mg twice daily and is the recommended dose for children and adolescents.
(© 2016, The American College of Clinical Pharmacology.)
فهرسة مساهمة: Keywords: HIV/AIDS; etravirine; pediatrics; pharmacodynamics; pharmacokinetics
المشرفين على المادة: 0 (HIV Protease Inhibitors)
0 (Nitriles)
0 (Pyridazines)
0 (Pyrimidines)
0 (Reverse Transcriptase Inhibitors)
0C50HW4FO1 (etravirine)
تواريخ الأحداث: Date Created: 20160410 Date Completed: 20170815 Latest Revision: 20201209
رمز التحديث: 20240829
DOI: 10.1002/jcph.746
PMID: 27060341
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-4604
DOI:10.1002/jcph.746