A Mass Balance-Based Semiparametric Approach to Evaluate Neonatal Erythropoiesis
Journal Title: The AAPS Journal - Year 2016, Vol 18, Issue 1
Abstract
Postnatal hemoglobin (Hb) production in anemic preterm infants is determined by several factors including the endogenous erythropoietin levels, allogeneic RBC transfusions administered to treat anemia, and developmental age. As a result, their postnatal Hb production rate can vary considerably. This work introduces a novel Hb mass balance-based semiparametric approach that utilizes infant blood concentrations of Hb from the first 30 postnatal days to estimate the amount of Hb produced and the erythropoiesis rate in newborn infants. The proposed method has the advantage of not relying on specific structural pharmacodynamic model assumptions to describe the Hb production, but instead utilizes simple mass balance principles and nonparametric regression analysis. The developed method was applied to the Hb data from 79 critically ill anemic very low birth weight preterm infants to evaluate the dynamic changes in erythropoiesis during the first month of life and to determine the inter-subject variability in Hb production. The estimated mean (±SD) cumulative amount of Hb produced by the infants over the first month of life was 6.6 ± 3.4 g (mean body weight, 0.768 kg), and the mean estimated body weight-scaled Hb production rate over the same period was 0.23 ± 0.12 g/day/kg. A significant positive correlation was observed between infant gestational age and the mean body weight-scaled Hb production rate over the first month of life (P < 0.05). We conclude that the proposed mathematical approach and its implementation provide a flexible framework to evaluate postnatal erythropoiesis in newborn infants.
Authors and Affiliations
Denison J. Kuruvilla, John A. Widness, Demet Nalbant, Robert L. Schmidt, Donald M. Mock, Peter Veng-Pedersen
Keywords
Related Articles
- EP ID EP680828
- DOI 10.1208/s12248-015-9831-8
- Views 67
- Downloads 0
Effect of nonionic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems
Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: Preliminary trial in humans
The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH...
Prediction of Hepatic Clearance in Human From In Vitro Data for Successful Drug Development
The in vivo metabolic clearance in human has been successfully predicted by using in vitro data of metabolic stability in cryopreserved preparations of human hepatocytes. In the predictions by human hepatocytes, the syst...
Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin
The aim of the study was to characterize the platelet count (PLT) dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO). Data from pati...
PTD-mediated Loading of Tumor-Seeking Lymphocytes with Prodrug-Activating Enzymes
Using the approach of peptide transduction domain (PTD)-mediated loading of interleukin-2(IL-2)-activated natural killer (A-NK) cells, tumor-seeking lymphocytes, with prodrug-activating enzymes, we primarily aim to gener...