Dale L Phelps1, Robert M Ward2, Rick L Williams3, Kristi L Watterberg4, Abbot R Laptook5, Lisa A Wrage3, Tracy L Nolen3, Timothy R Fennell6, Richard A Ehrenkranz7, Brenda B Poindexter8, C Michael Cotten9, Mikko K Hallman10, Ivan D Frantz11, Roger G Faix2, Kristin M Zaterka-Baxter3, Abhik Das12, M Bethany Ball13, T Michael O'Shea14, Conra Backstrom Lacy4, Michele C Walsh15, Seetha Shankaran16, Pablo J Sánchez17, Edward F Bell18, Rosemary D Higgins19. 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.
RCT Entities:
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.
Authors: C A Friedman; J McVey; M J Borne; M James; W L May; D M Temple; K K Robbins; C J Miller; J E Rawson Journal: J Pediatr Ophthalmol Strabismus Date: 2000 Mar-Apr Impact factor: 1.402
Authors: Karen J Schimpf; Claudia C Meek; Richard D Leff; Dale L Phelps; Daniel J Schmitz; Christopher T Cordle Journal: Biomed Chromatogr Date: 2015-05-26 Impact factor: 1.902
Authors: Dale L Phelps; Kristi L Watterberg; Tracy L Nolen; Carol A Cole; C Michael Cotten; William Oh; Brenda B Poindexter; Kristin M Zaterka-Baxter; Abhik Das; Conra Backstrom Lacy; Ann Marie Scorsone; Michele C Walsh; Edward F Bell; Kathleen A Kennedy; Kurt Schibler; Gregory M Sokol; Matthew M Laughon; Satyanarayana Lakshminrusimha; William E Truog; Meena Garg; Waldemar A Carlo; Abbot R Laptook; Krisa P Van Meurs; David P Carlton; Amanda Graf; Sara B DeMauro; Luc P Brion; Seetha Shankaran; Faruk H Orge; Richard J Olson; Helen Mintz-Hittner; Michael B Yang; Kathryn M Haider; David K Wallace; Mina Chung; Denise Hug; Irena Tsui; Martin S Cogen; John P Donahue; Michael Gaynon; Amy K Hutchinson; Don L Bremer; Graham Quinn; Yu-Guang He; William R Lucas; Timothy W Winter; Stephen D Kicklighter; Kartik Kumar; Patricia R Chess; Tarah T Colaizy; Anna Marie Hibbs; Namasivayam Ambalavanan; Heidi M Harmon; Elisabeth C McGowan; Rosemary D Higgins Journal: JAMA Date: 2018-10-23 Impact factor: 56.272
Authors: Abhik Das; Jon Tyson; Claudia Pedroza; Barbara Schmidt; Marie Gantz; Dennis Wallace; William E Truog; Rosemary D Higgins Journal: Semin Perinatol Date: 2016-06-22 Impact factor: 3.300
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; 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: Pediatr Res Date: 2016-04-13 Impact factor: 3.756
Authors: Leeann R Pavlek; Brian K Rivera; Charles V Smith; Joanie Randle; Cory Hanlon; Kristi Small; Edward F Bell; Matthew A Rysavy; Sara Conroy; Carl H Backes Journal: J Pediatr Date: 2021-04-21 Impact factor: 6.314
Authors: Luc P Brion; Dale L Phelps; Robert M Ward; Tracy L Nolen; N Mikko K Hallman; Abhik Das; Daniel J Zaccaro; M Bethany Ball; Kristi L Watterberg; Ivan D Frantz; C Michael Cotten; Brenda B Poindexter; William Oh; Ralph A Lugo; Krisa P Van Meurs; T Michael O'Shea; Kristin M Zaterka-Baxter; Rosemary D Higgins Journal: J Perinatol Date: 2020-09-15 Impact factor: 2.521
Authors: Jenna E Koschnitzky; Richard F Keep; David D Limbrick; James P McAllister; Jill A Morris; Jennifer Strahle; Yun C Yung Journal: Fluids Barriers CNS Date: 2018-03-27