Prematurity of Fetus
Conditions
Keywords
oseltamivir, influenza, neonate, premature, pharmacokinetics
Brief summary
Oseltamivir dosing in infants \< 3 months of age is based on a single pharmacokinetic study in 20 infants from a single center. This dataset is limited by a lack of robustness, because only 1 sample was collected from each participant. The investigators obtained two blood samples each from infants receiving oseltamivir after obtaining informed consent from the infant's parents. The investigators propose to analyze the blood samples to determine the amount of oseltamivir in the infant's blood. Measurement of these values will increase the understanding of the absorption and elimination of oseltamivir in preterm and term infants, and improve our ability to provide the correct doses to this high risk population.
Interventions
DRUGOseltamivir
Treatment dose was oseltamivir 3 mg/kg/dose by mouth (PO) twice daily. Prophylactic dose was oseltamivir 1 mg/kg/dose PO once daily to infants \< 28 weeks postmenstrual age (PMA), 1 mg/kg/dose PO twice daily to infants 28 - 38 weeks PMA, and 3 mg/kg/dose PO once daily to infants \> 38 weeks PMA. Dosing in infants \< 28 weeks PMA was chosen based on unpublished data from Acosta et al. This data was obtained from phone contact with Dr. Peter Gal, co-author of the study. Dosing in infants 28 - 38 weeks PMA was chosen based on published data from Acosta et al.1 Dosing in infants \> 38 weeks PMA and less than 3 months postnatal age was chosen based on data from Kimberlin et al. Dosing in infants \> 38 weeks PMA and greater than 3 months postnatal age was per the recommendations of the Advisory Committee on Immunization Practices of the United States Department of Health and Human Services.
Sponsors
Genentech, Inc.
Washington University School of Medicine
St. Louis Children's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
Inclusion criteria
* All neonates and infants in the NICU at St. Louis Children's Hospital who received oseltamivir for treatment of or exposure to influenza virus type A were considered eligible for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oseltamivir pharmacokinetics in neonates and infants | Two sample points, one 0-3 hours (baseline) and one 3-24 hours post dose | Pharmacokinetic parameters calculated for individual subjects will include apparent distribution volume and elimination half-life of oseltamivir (OST) and OST carboxylate (CBX). Area under the plasma concentration versus time curve (AUC) of OST and OST CBX will be determined using the trapezoidal method. A population pharmacokinetic model will be generated based on pooled pharmacokinetic data (2-compartment model for OST and 1-compartment model for OST CBX) utilizing maximum likelihood estimation. A weight-based dosing table will be generated to provide AUC exposures comparable to adults. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oseltamivir target level attainment | Two sample points, one 0-3 hours (baseline) and one 3-24 hours post dose | OST target level attainment of the currently recommended dosing regimen in neonates and infants will be calculated. Currently recommended doses were utilized for all neonates and infants in our cohort. The target level attainment in this cohort will be calculated. |
Countries
United States
Outcome results
None listed