Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

HIV treatment of neonates requires identifying appropriate antiretroviral dosing regimens. Our aims were to characterize raltegravir elimination kinetics in low birth weight (LBW) neonates after maternal dosing and to develop a pharmacokinetic model to predict raltegravir plasma concentrations for term and preterm neonates. Mothers living with HIV who received raltegravir during pregnancy and their LBW neonates participated in IMPAACT P1097 study. Up to 6 serial plasma samples were collected from each infant over the first 2 postnatal weeks to characterize raltegravir elimination. Safety laboratory evaluations were obtained, and infants were monitored for 6 weeks for signs of raltegravir toxicity. An integrated maternal-neonatal pharmacokinetic model was developed to predict neonatal raltegravir plasma concentrations. Sixteen mothers and their 18 LBW neonates were enrolled. The median (range) raltegravir elimination half-life was 24.4 (10.1-83) hours (N = 17 neonates). No adverse events related to raltegravir in utero exposure were observed. Pharmacokinetic modeling revealed that raltegravir clearance in full-term LBW neonates was well described by allometric scaling but clearance in preterm LBW neonates was better described using slower clearance maturation kinetics. Simulations suggest receipt of the current dosing recommendations in a 34-week gestation neonate would result in plasma concentrations up to 2.5-fold higher than those observed in full-term LBW infants. Modeling suggests that prematurity reduces raltegravir clearance and a modified raltegravir dosing regimen will be necessary to avoid elevated plasma raltegravir concentrations.

Citation

Diana F Clarke, Jos Lommerse, Edward P Acosta, Mae P Cababasay, Jiajia Wang, Stephen A Spector, Anne Chain, Elizabeth Smith, Hedy Teppler, Rohan Hazra, Kat Calabrese, Bobbie Graham, Stephanie Popson, Yvonne Bryson, Mark Mirochnick, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1097 Study Team. Impact of Low Birth Weight and Prematurity on Neonatal Raltegravir Pharmacokinetics: Impaact P1097. Journal of acquired immune deficiency syndromes (1999). 2020 Dec 15;85(5):626-634

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 32925360

View Full Text