Journal article
Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk
Pediatric research, Vol.74(6), pp.721-729
12/2013
DOI: 10.1038/pr.2013.162
PMCID: PMC3962781
PMID: 24067395
Abstract
Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia, and reduced severe retinopathy of prematurity in two randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed before efficacy trials.
Infants born in 23-29 wk of gestation were randomized to a single intravenous (i.v.) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed-effects approach. Safety outcomes were recorded.
A single-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age strata, and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance was 0.0679 l/kg/h, endogenous production was 2.67 mg/kg/h, and the half-life was 5.22 h when modeled without the covariates. During the first 12 h, renal inositol excretion quadrupled in the 120 mg/kg group, returning to near-baseline value after 48 h. There was no diuretic side effect. No significant differences in adverse events occurred among the three groups (P > 0.05).
A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v. inositol.
Details
- Title: Subtitle
- Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk
- Creators
- Dale L Phelps - The School of Medicine and Dentistry, University of Rochester, Rochester, New YorkRobert M Ward - Department of Pediatrics, Division of Neonatology, School of Medicine, University of Utah, Salt Lake City, UtahRick L Williams - Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North CarolinaKristi L Watterberg - University of New Mexico Health Sciences Center, Albuquerque, New MexicoAbbot R Laptook - Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode IslandLisa A Wrage - Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North CarolinaTracy L Nolen - Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North CarolinaTimothy R Fennell - Pharmacology and Toxicology Division, RTI International, Research Triangle Park, North CarolinaRichard A Ehrenkranz - Department of Pediatrics, Yale University School of Medicine, New Haven, ConnecticutBrenda B Poindexter - Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IndianaC Michael Cotten - Department of Pediatrics, Duke University, Durham, North CarolinaMikko K Hallman - 1] Department of Pediatrics, University of Oulu, Oulu, Finland Oulu University Hospital, Oulu, FinlandIvan D Frantz III - Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MassachusettsRoger G Faix - Department of Pediatrics, Division of Neonatology, School of Medicine, University of Utah, Salt Lake City, UtahKristin M Zaterka-Baxter - Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North CarolinaAbhik Das - Statistics and Epidemiology Unit, RTI International, Rockville, MarylandM Bethany Ball - Division of Neonatal and Developmental Medicine, Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CaliforniaT Michael O'Shea - Wake Forest University School of Medicine, Winston-Salem, North CarolinaConra Backstrom Lacy - University of New Mexico Health Sciences Center, Albuquerque, New MexicoMichele C Walsh - Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OhioSeetha Shankaran - Department of Pediatrics, Wayne State University, Detroit, MichiganPablo J Sánchez - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TexasEdward F Bell - Department of Pediatrics, University of Iowa, Iowa City, IowaRosemary D Higgins - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.74(6), pp.721-729
- DOI
- 10.1038/pr.2013.162
- PMID
- 24067395
- PMCID
- PMC3962781
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Grant note
- U10 HD053124 / NICHD NIH HHS UG1 HD053089 / NICHD NIH HHS UL1 TR000041 / NCATS NIH HHS M01 RR000030 / NCRR NIH HHS U10 HD037261 / NICHD NIH HHS UL1 RR024160 / NCRR NIH HHS M01 RR000125 / NCRR NIH HHS U10 HD053119 / NICHD NIH HHS U10 HD027871 / NICHD NIH HHS M01 RR000054 / NCRR NIH HHS U10 HD040498 / NICHD NIH HHS UG1 HD053109 / NICHD NIH HHS M01 RR000080 / NCRR NIH HHS M01 RR000997 / NCRR NIH HHS U10 HD040492 / NICHD NIH HHS U10 HD036790 / NICHD NIH HHS UL1 RR024139 / NCRR NIH HHS U10 HD037249 / NICHD NIH HHS U10 HD040521 / NICHD NIH HHS U10 HD053089 / NICHD NIH HHS U10 HD040689 / NICHD NIH HHS U10 HD027904 / NICHD NIH HHS U10 HD053109 / NICHD NIH HHS UL1 TR001449 / NCATS NIH HHS U10 HD027856 / NICHD NIH HHS U10 HD027880 / NICHD NIH HHS U10 HD021364 / NICHD NIH HHS U10 HD068278 / NICHD NIH HHS M01 RR000633 / NCRR NIH HHS U10 HD045993 / NICHD NIH HHS U10 HD046000 / NICHD NIH HHS M01 RR000750 / NCRR NIH HHS U10 HD021385 / NICHD NIH HHS M01 RR000059 / NCRR NIH HHS M01 RR000064 / NCRR NIH HHS UG1 HD068278 / NICHD NIH HHS
- Language
- English
- Date published
- 12/2013
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093482402771
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