Journal article
Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants
Pediatric research, Vol.80(2), pp.209-217
08/2016
DOI: 10.1038/pr.2016.97
PMCID: PMC5198845
PMID: 27074126
Abstract
Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization.
Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored.
At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so.
Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial.
Details
- Title: Subtitle
- Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants
- Creators
- Dale L Phelps - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New YorkRobert M Ward - Department of Pediatrics, and Pediatric Pharmacology, University of Utah School of Medicine, Salt Lake City, UtahRick L Williams - Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaTracy L Nolen - Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaKristi L Watterberg - Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New MexicoWilliam Oh - Department of Pediatrics, Women & Infants' Hospital Brown University, Providence, Rhode IslandMichael Goedecke - Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaRichard A Ehrenkranz - Department of Pediatrics, Yale University School of Medicine, New Haven, ConnecticutTimothy Fennell - Pharmacology and Toxicology Division, RTI International, Research Triangle Park, North CarolinaBrenda B Poindexter - Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IndianaC Michael Cotten - Department of Pediatrics, Duke University, Durham, North CarolinaMikko Hallman - PEDEGO Research Center, and MRC Oulu, and Oulu University Hospital, Oulu, FinlandIvan D Frantz III - Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, MassachusettsRoger G Faix - Department of Pediatrics, and Pediatric Pharmacology, University of Utah School of Medicine, Salt Lake City, UtahKristin M Zaterka-Baxter - Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaAbhik Das - Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, MarylandM Bethany Ball - Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CaliforniaConra Backstrom Lacy - Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New MexicoMichele C Walsh - Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioWaldemar A Carlo - Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AlabamaPablo J Sánchez - Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TexasEdward F Bell - Department of Pediatrics, University of Iowa, Iowa City, IowaSeetha Shankaran - Department of Pediatrics, Wayne State University, Detroit, MichiganDavid P Carlton - Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GeorgiaPatricia R Chess - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New YorkRosemary 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.80(2), pp.209-217
- DOI
- 10.1038/pr.2016.97
- PMID
- 27074126
- PMCID
- PMC5198845
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Grant note
- U10 HD053124 / NICHD NIH HHS UG1 HD053089 / NICHD NIH HHS UG1 HD040492 / NICHD NIH HHS UG1 HD027851 / NICHD NIH HHS M01 RR000039 / NCRR NIH HHS UG1 HD027904 / NICHD NIH HHS M01 RR000030 / NCRR NIH HHS U10 HD037261 / NICHD NIH HHS M01 RR000125 / NCRR NIH HHS U10 HD053119 / NICHD NIH HHS U10 HD027871 / NICHD NIH HHS UL1 TR000442 / NCATS NIH HHS M01 RR000054 / NCRR NIH HHS UG1 HD027880 / 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 HD040521 / NICHD NIH HHS M01 RR000044 / NCRR NIH HHS U10 HD053089 / NICHD NIH HHS U10 HD045986 / NICHD NIH HHS U10 HD040689 / NICHD NIH HHS U10 HD027904 / NICHD NIH HHS UG1 HD068263 / NICHD NIH HHS UG1 HD021385 / NICHD NIH HHS U10 HD053109 / NICHD NIH HHS UG1 HD087226 / NICHD NIH HHS M01 RR000032 / NCRR NIH HHS U10 HD027856 / NICHD NIH HHS UL1 TR000454 / NCATS NIH HHS U10 HD027880 / NICHD NIH HHS U10 HD021364 / NICHD NIH HHS U10 HD027851 / NICHD NIH HHS M01 RR000633 / NCRR NIH HHS U10 HD034216 / NICHD NIH HHS M01 RR000750 / NCRR NIH HHS U10 HD021385 / NICHD NIH HHS M01 RR000059 / NCRR NIH HHS UG1 HD034216 / NICHD NIH HHS M01 RR000064 / NCRR NIH HHS UG1 HD027856 / NICHD NIH HHS UG1 HD027853 / NICHD NIH HHS UG1 HD068278 / NICHD NIH HHS
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093221102771
Metrics
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