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Pediatr Res. 2016 Aug;80(2):209-17. doi: 10.1038/pr.2016.97. Epub 2016 Apr 13.

Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants.

Author information

1
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York.
2
Department of Pediatrics, and Pediatric Pharmacology, University of Utah School of Medicine, Salt Lake City, Utah.
3
Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina.
4
Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
5
Department of Pediatrics, Women & Infants' Hospital Brown University, Providence, Rhode Island.
6
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
7
Pharmacology and Toxicology Division, RTI International, Research Triangle Park, North Carolina.
8
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
9
Department of Pediatrics, Duke University, Durham, North Carolina.
10
PEDEGO Research Center, and MRC Oulu, and Oulu University Hospital, Oulu, Finland.
11
Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts.
12
Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland.
13
Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California.
14
Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
15
Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham, Birmingham, Alabama.
16
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
17
Department of Pediatrics, University of Iowa, Iowa City, Iowa.
18
Department of Pediatrics, Wayne State University, Detroit, Michigan.
19
Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
20
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
27074126
PMCID:
PMC5198845
DOI:
10.1038/pr.2016.97
[Indexed for MEDLINE]
Free PMC Article

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