Open AccessRaltegravir Pharmacokinetics in Neonates Following Maternal Dosing
Author(s) -
Diana F. Clarke,
Edward P. Acosta,
Matthew L. Rizk,
Yvonne J. Bryson,
Stephen A. Spector,
Lynne Mofenson,
Edward Handelsman,
Hedy Teppler,
Carolee Welebob,
Deborah Persaud,
Mae Cababasay,
Jia Jia Wang,
Mark Mirochnick
Publication year - 2014
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - Uncategorized
Resource type - Journals
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/qai.0000000000000316
Subject(s) - raltegravir , medicine , pharmacokinetics , therapeutic drug monitoring , pharmacology , dosing , pediatrics , viral load , human immunodeficiency virus (hiv) , antiretroviral therapy , immunology
: International Maternal Pediatric Adolescent AIDS Clinical Trials P1097 was a multicenter trial to determine washout pharmacokinetics and safety of in utero/intrapartum exposure to raltegravir in infants born to HIV-infected pregnant women receiving raltegravir-based antiretroviral therapy. Twenty-two mother-infant pairs were enrolled; evaluable pharmacokinetic data were available from 19 mother-infant pairs. Raltegravir readily crossed the placenta, with a median cord blood/maternal delivery plasma raltegravir concentration ratio of 1.48 (range, 0.32-4.33). Raltegravir elimination was highly variable and extremely prolonged in some infants; [median t1/2 26.6 (range, 9.3-184) hours]. Prolonged raltegravir elimination likely reflects low neonatal UGT1A1 enzyme activity and enterohepatic recirculation. Excessive raltegravir concentrations must be avoided in the neonate because raltegravir at high plasma concentrations may increase the risk of bilirubin neurotoxicity. Subtherapeutic concentrations, which could lead to inadequate viral suppression and development of raltegravir resistance, must also be avoided. Two ongoing International Maternal Pediatric Adolescent AIDS Clinical Trials studies are further investigating the pharmacology of raltegravir in neonates.