Pharmacokinetics of Oseltamivir in Newborns and Infants
|ClinicalTrials.gov Identifier: NCT01388439|
Recruitment Status : Completed
First Posted : July 6, 2011
Last Update Posted : July 6, 2011
|Condition or disease||Intervention/treatment|
|Prematurity of Fetus||Drug: Oseltamivir|
|Study Type :||Observational|
|Actual Enrollment :||19 participants|
|Official Title:||Pharmacokinetics of Oseltamivir in Newborns and Infants|
|Study Start Date :||January 2011|
|Primary Completion Date :||January 2011|
|Study Completion Date :||January 2011|
One infant in the Neonatal Intensive Care Unit (NICU) at St. Louis Children's Hospital experienced respiratory decompensation and tested positive for influenza virus type A by fluorescent antibody stain performed on a nasopharyngeal swab. This infant received treatment doses of oseltamivir. Subsequently, 27 other infants received oseltamivir prophylaxis for exposure to influenza virus type A. Exposed infants were those who shared a primary medical team, nursing care, respiratory therapist, physical therapist, or occupational therapist with the influenza A positive infant. Prophylaxis was deemed necessary by the attending neonatologist after consultation with the Infectious Diseases Division of the Department of Pediatrics at the Washington University School of Medicine.
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 28 weeks PMA was chosen based on unpublished data from Acosta et al.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.
- Oseltamivir pharmacokinetics in neonates and infants [ Time Frame: 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.
- Oseltamivir target level attainment [ Time Frame: 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.
Biospecimen Retention: Samples With DNA
Two whole blood samples (0.5 mL) were obtained at steady state (day 3 of therapy or later), collected in K3EDTA mini-collection tubes labeled with a sample identification number. Plasma specimens were separated by centrifugation of 1500 g for 10 minutes at 4 degrees Celsius within 60 minutes of sample collection. Plasma supernatant was transferred into a cryovial labeled with the same sample identification number. Cryovials were immediately stored at -70 degrees Celsius. Sample obtainment and processing was directly supervised by the principle investigator.
The blood samples are currently being stored at -70 degrees Celsius in a research laboratory operated by medical faculty of the Washington University School of Medicine Department of Pediatrics Division of Infectious Diseases in the McDonnell Medical Sciences Building.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01388439
|United States, Missouri|
|St. Louis Children's Hosptial|
|St. Louis, Missouri, United States, 63110|