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Clinical Trial
. 2014 Nov 1;67(3):310-5.
doi: 10.1097/QAI.0000000000000316.

Raltegravir pharmacokinetics in neonates following maternal dosing

Diana F Clarke  1 , 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, JiaJia Wang, Mark Mirochnick; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1097 Study Team
Collaborators, Affiliations
Clinical Trial

Raltegravir pharmacokinetics in neonates following maternal dosing

Diana F Clarke et al. J Acquir Immune Defic Syndr. .

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.

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Conflict of interest statement

Conflicts of Interest

All other authors report no potential conflicts.

All authors have submitted the ICMJE form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1
Figure 1
Figure 1A. Raltegravir concentrations in cord blood (crosses) and maternal plasma at delivery (open diamonds). Figure 1B. Ratio of cord blood to maternal plasma delivery concentration (open triangles) plotted against time between maternal dosing and delivery.
Figure 2
Figure 2
Individual plots of raltegravir concentration vs. time after birth. Heavy dashed line represents median concentration at each sampling time point. Light dashed line represents the raltegravir IC95 for wild type virus of 14 ng/mL.
See this image and copyright information in PMC

References

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