Raltegravir Pharmacokinetics in Neonates Following Maternal Dosing

被引：37

作者：

Clarke, Diana F. ^{[1
]}

Acosta, Edward P. ^{[2
]}

Rizk, Matthew L. ^{[3
]}

Bryson, Yvonne J. ^{[4
]}

Spector, Stephen A. ^{[5
,6
]}

Mofenson, Lynne M. ^{[7
]}

Handelsman, Edward ^{[8
]}

Teppler, Hedy ^{[3
]}

Welebob, Carolee ^{[3
]}

Persaud, Deborah ^{[9
]}

Cababasay, Mae P. ^{[10
]}

Wang, JiaJia ^{[10
]}

Mirochnick, Mark ^{[11
]}

机构：

[1] Boston Med Ctr, Sect Pediat Infect Dis, Boston, MA USA

[2] Univ Alabama Birmingham, Div Clin Pharmacol, Birmingham, AL 35294 USA

[3] Merck & Co Inc, Whitehouse Stn, NJ USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat Infect Dis, Los Angeles, CA 90095 USA

[5] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[6] Rady Childrens Hosp San Diego, La Jolla, CA USA

[7] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA

[8] NIH, Div AIDS, Bethesda, MD 20892 USA

[9] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[10] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA

[11] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA

来源：

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES | 2014年 / 67卷 / 03期

关键词：

raltegravir pharmacokinetics; neonates; TRANSPLACENTAL TRANSFER; BILIRUBIN;

D O I：

10.1097/QAI.0000000000000316

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 t(1/2) 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.

引用

页码：310 / 315

页数：6

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