Pharmacokinetics of Efavirenz at a High Dose of 25 Milligrams per Kilogram per Day in Children 2 to 3 Years Old
| Autor: | Karen Malateste, Madeleine Amorissani-Folquet, Naïm Bouazza, Déborah Hirt, Stéphane Blanche, Gabrielle Lui, Jean-Marc Tréluyer, Caroline Yonaba, Sylvie Ouédraogo, François Tanoh Eboua, Frantz Foissac, Désiré Lucien Dahourou, Valériane Leroy, Claire Pressiat, Véronique Mea-Assande |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyclopropanes Male medicine.medical_specialty Efavirenz Anti-HIV Agents Gastroenterology Drug Administration Schedule Lopinavir 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Therapeutic index Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) 030212 general & internal medicine Pharmacology business.industry Liter Bayes Theorem 030112 virology NONMEM Benzoxazines Infectious Diseases chemistry Alkynes Child Preschool Toxicity Female business medicine.drug Blood sampling |
| Popis: | The MONOD ANRS 12206 trial was designated to assess simplification of a successful lopinavir (LPV)-based antiretroviral treatment in HIV-infected children younger than 3 years of age using efavirenz (EFV; 25 mg/kg of body weight/day) to preserve the class of protease inhibitors for children in that age group. In this substudy, EFV concentrations were measured to check the consistency of an EFV dose of 25 mg/kg and to compare it with the 2016 FDA recommended dose. Fifty-two children underwent blood sampling for pharmacokinetic study at 6 months and 12 months after switching to EFV. We applied a Bayesian approach to derive EFV pharmacokinetic parameters using the nonlinear mixed-effect modeling (NONMEM) program. The proportion of midinterval concentrations 12 h after drug intake (C12 h) corresponding to the EFV therapeutic pharmacokinetic thresholds (1 to 4 mg/liter) was assessed according to different dose regimens (25 mg/kg in the MONOD study versus the 2016 FDA recommended dose). With both the 25 mg/kg/day dose and the 2016 FDA recommended EFV dose, simulations showed that the majority ofC12 hvalues were within the therapeutic range (62.6% versus 62.8%). However, there were more children underexposed with the 2016 FDA recommended dose (11.6% versus 1.2%). Conversely, there were more concentrations above the threshold of toxicity with the 25 mg/kg dose (36.2% versus 25.6%), withC12 hvalues of up to 15 mg/liter. Only 1 of 52 children was switched back to LPV because of persistent sleeping disorders, but hisC12 hvalue was within therapeutic ranges. A high EFV dose of 25 mg/kg per day in children under 3 years old achieved satisfactory therapeutic effective levels. However, the 2016 FDA recommended EFV dose appeared to provide more acceptable safe therapeutic profiles. (This study has been registered at ClinicalTrials.gov under identifier NCT01127204.) |
| Databáze: | OpenAIRE |
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