We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Population Pharmacokinetics of Darbepoetin Alfa in Conjunction with Hypothermia for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.
- Authors
Roberts, Jessica; Stockmann, Chris; Ward, Robert; Beachy, Joanna; Baserga, Mariana; Spigarelli, Michael; Sherwin, Catherine; Roberts, Jessica K; Ward, Robert M; Baserga, Mariana C; Spigarelli, Michael G; Sherwin, Catherine M T
- Abstract
<bold>Aim: </bold>The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia.<bold>Methods: </bold>Neonates ≥36 weeks gestation and <12 h postpartum with moderate to severe hypoxic-ischemic encephalopathy who were undergoing hypothermia treatment were recruited in this randomized, multicenter, investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa treatment groups were evaluated: 2 and 10 µg/kg. Serum erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay. Monolix 4.3.1 was used to estimate darbepoetin alfa clearance and volume of distribution. Covariates tested included: birthweight, gestational age, postnatal age, postmenstrual age, sex, Sarnat score, and study site.<bold>Results: </bold>Darbepoetin alfa pharmacokinetics were well described by a one-compartment model with exponential error. Clearance and the volume of distribution were scaled by birthweight (centered on the mean) a priori. Additionally, gestational age (also centered on the mean) significantly affected darbepoetin alfa clearance. Clearance and volume of distribution were estimated as 0.0465 L/h (95% confidence interval 0.0392-0.0537) and 1.58 L (95% confidence interval 1.29-1.87), respectively.<bold>Conclusions: </bold>A one-compartment model successfully described the pharmacokinetics of darbepoetin alfa among hypothermic neonates treated for hypoxic-ischemic encephalopathy. Clearance decreased with increasing gestational age.
- Subjects
PHARMACOKINETICS; DARBEPOETIN alfa; HYPOTHERMIA; HYPOXEMIA; NEONATAL diseases; ENZYME-linked immunosorbent assay
- Publication
Clinical Pharmacokinetics, 2015, Vol 54, Issue 12, p1237
- ISSN
0312-5963
- Publication type
journal article
- DOI
10.1007/s40262-015-0286-y