Use of Modeling and Simulations to Determine Raltegravir Dosing in Neonates: A Model for Safely and Efficiently Determining Appropriate Neonatal Dosing Regimens: IMPAACT P1110.
J Acquir Immune Defic Syndr
; 82(4): 392-398, 2019 12 01.
Article
en En
| MEDLINE
| ID: mdl-31658182
ABSTRACT
BACKGROUND:
Population modeling and simulations can be used to facilitate the conduct of phase I studies to develop safe and effective dosing regimens in neonates.SETTING:
P1110 is an international, multicenter trial to determine safe and effective raltegravir doses in neonates at risk for HIV infection.METHODS:
P1110 used a 2-cohort adaptive design incorporating population pharmacokinetic modeling and simulations. An initial cohort of neonates received 2 single oral doses of raltegravir with standard-of-care therapy for prevention of perinatal transmission-one within 48 hours of birth and a second at 7-10 days of life. Raltegravir concentration data after administration of these doses were combined with data from a previous study of infants aged 4 weeks to 2 years. The combined database was used for population pharmacokinetic modeling and simulations to select a daily dosing regimen for investigation in a second cohort of neonates.RESULTS:
Raltegravir concentration data from 6 neonates were combined with data from infants aged 4 weeks to 2 years receiving raltegravir twice daily. The combined data set allowed for successful development of a population pharmacokinetic model with reasonable precision of parameter estimates. Monte Carlo simulations were run to evaluate potential daily dosing regimens from birth to 6 weeks of age, allowing for selection of a regimen to be evaluated in a subsequent cohort of neonates receiving chronic raltegravir dosing.CONCLUSIONS:
An adaptive design incorporating population pharmacokinetic modeling and simulations was used to select a developmentally appropriate neonatal raltegravir dosing regimen in the first 6 weeks of life.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
Fármacos Anti-VIH
/
Raltegravir Potásico
Tipo de estudio:
Clinical_trials
/
Health_economic_evaluation
Idioma:
En
Revista:
J Acquir Immune Defic Syndr
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2019
Tipo del documento:
Article