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

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.

• Authors: Dale L Phelps, Robert M Ward, Rick L Williams, Tracy L Nolen, Kristi L Watterberg, William Oh, Michael Goedecke, Richard A Ehrenkranz, Timothy Fennell, Brenda B Poindexter, C Michael Cotten, Mikko Hallman, Ivan D Frantz 3rd, Roger G Faix, Kristin M Zaterka-Baxter, Abhik Das, M Bethany Ball, Conra Backstrom Lacy, Michele C Walsh, Waldemar A Carlo, Pablo J Sánchez, Edward F Bell, Seetha Shankaran, David P Carlton, Patricia R Chess, Rosemary D Higgins
• Journal: Pediatric research (Pediatr Res) Vol. 80 Issue 2 Pg. 209-17 (08 2016) ISSN: 1530-0447 [Electronic] United States
• PMID: 27074126 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inositol

Topics

• Bronchopulmonary Dysplasia (complications)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Infant
• Infant, Newborn
• Infant, Premature
• Infusions, Intravenous
• Inositol (administration & dosage, pharmacokinetics)
• Male
• Patient Safety
• Respiratory Distress Syndrome, Newborn (complications, drug therapy)
• Retinopathy of Prematurity (complications)
• Time Factors