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Pediatr Res. 2013 Dec;74(6):721-9. doi: 10.1038/pr.2013.162. Epub 2013 Sep 4.

Pharmacokinetics and safety of a single intravenous dose of myo-inositol in preterm infants of 23-29 wk.

Author information

1
The School of Medicine and Dentistry, University of Rochester, Rochester, New York.
2
Department of Pediatrics, Division of Neonatology, School of Medicine, University of Utah, Salt Lake City, Utah.
3
Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina.
4
University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
5
Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island.
6
Pharmacology and Toxicology Division, RTI International, Research Triangle Park, North Carolina.
7
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
8
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
9
Department of Pediatrics, Duke University, Durham, North Carolina.
10
1] Department of Pediatrics, University of Oulu, Oulu, Finland [2] Oulu University Hospital, Oulu, Finland.
11
Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts.
12
Statistics and Epidemiology Unit, RTI International, Rockville, Maryland.
13
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California.
14
Wake Forest University School of Medicine, Winston-Salem, North Carolina.
15
Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
16
Department of Pediatrics, Wayne State University, Detroit, Michigan.
17
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
18
Department of Pediatrics, University of Iowa, Iowa City, Iowa.
19
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v. inositol.

PMID:
24067395
PMCID:
PMC3962781
DOI:
10.1038/pr.2013.162
[Indexed for MEDLINE]
Free PMC Article

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