Raltegravir pharmacokinetics in neonates following maternal dosing

Diana F. Clarke, Edward P. Acosta, Matthew L. Rizk, Yvonne J. Bryson, Stephen A. Spector, Lynne M. Mofenson, Edward Handelsman, Hedy Teppler, Carolee Welebob, Deborah Persaud, Mae P. Cababasay, Jia Jia Wang, Mark Mirochnick

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)310-315
Number of pages6
JournalJournal of acquired immune deficiency syndromes
Volume67
Issue number3
DOIs
StatePublished - Jan 1 2014

Keywords

  • Neonates
  • Raltegravir pharmacokinetics

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Clarke, D. F., Acosta, E. P., Rizk, M. L., Bryson, Y. J., Spector, S. A., Mofenson, L. M., Handelsman, E., Teppler, H., Welebob, C., Persaud, D., Cababasay, M. P., Wang, J. J., & Mirochnick, M. (2014). Raltegravir pharmacokinetics in neonates following maternal dosing. Journal of acquired immune deficiency syndromes, 67(3), 310-315. https://doi.org/10.1097/QAI.0000000000000316