Pharmacokinetics of Dexamethasone following Single-Dose Intravenous Administration to Extremely Low Birth Weight Infants

Abstract

The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low birth weight infants of mean (± SD) gestational age 25.6 ±0.5 weeks suffering bronchopulmonary dysplasia. A mean peak dexamethasone concentration of 250.5 ± 70.7 ng/ml was obtained following an intravenous bolus dose (0.369 ± 0.04 mg/kg dexamethasone) of dexamethasone sodium phosphate. Dexamethasone was measured in plasma by HPLC. Mean clearance (0.143 ± 0.028 litres/kg/h) was approximately half that reported previously in children and adults, while the half-life (9.26 ± 3.34 h) was 2- to 3-fold longer than in these patients. The volume of distribution (1.9 ± 0.483 litres/kg) was larger than reported in a previous study in adults, but was similar to that determined in pediatric and adult patients in another study.

Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

“…Nevertheless, in undifferentiated PC12 cells undergoing active mitosis, we obtained clear inhibition of cell replication at DEX concentrations as low as 0.01 mM, more than an order of magnitude below the concentrations expected from typical therapy (Charles et al, 1993;Gilstrap et al, 1995;Osathanondh et al, 1977). The effect did not wane with prolonged exposure, in keeping with the situation in the developing fetus, where glucocorticoid receptors typically do not downregulate or desensitize, whereas they do in the adult (Ghosh et al, 2000).…”

“…Accordingly, the present study utilized DEX concentrations as low as 0.01 mM and up to 10 mM. In humans, the typical levels after administration of a relatively low dose of 0.1-0.15 mg/kg is about 0.6 mM when given directly to a preterm infant, or 0.06 mM in the fetus when DEX is given to the mother (Charles et al, 1993;Osathanondh et al, 1977); as the recommended dose in preterm delivery is about three times higher (Gilstrap et al, 1995), our chosen dose range clearly spans the subtherapeutic to supratherapeutic range. We evaluated three different critical neurodevelopmental stages: undifferentiated cells that are undergoing active mitosis, early stages of differentiation in which cells are still dividing but are undergoing the transition to neuritic development and phenotypic specialization, and mid-differentiation in which the same processes are further developed.…”

Dexamethasone Increases Hippocampal Neuronal Apoptosis in a Rabbit Model of Escherichia coli Meningitis

“…Dexamethasone (Ratiopharm, Ulm, Germany) was administered in a dose of 1 mg/kg body weight to compensate different clearance rates between rabbits and infants (usual dose in children: 0.15 mg/kg body weight). In humans, pharmacokinetic data are available for doses of 0.10 -0.37 mg/kg body weight [clearance of healthy adult men: 0.189 L/h/kg (24); clearance in neonates: 0.143 L/h/kg (25)]. In rabbits, the dexamethasone clearance was determined after intravenous application of 2 or 10 mg/kg body weight: The clearance decreased with higher doses, suggesting nonlinear pharmacokinetics (26).…”

Postnatal betamethasone vs dexamethasone in premature infants with bronchopulmonary dysplasia: a pilot study

“…18,19 Furthermore, these effects may arise from betamethasone's preferred pharmacological profile and the method we used for administration, which should produce a more stable and sustained release, a longer half-life and slower clearance due to intramuscularly administered betamethasone rather than intravenous dexamethasone treatment. 27,28 In the United States, about 5000 to 12 000 newborns develop BPD every year which is associated with an increased risk of cerebral palsy and neurodevelopmental delay. 29,30 In addition, every 10 days of ventilator therapy is associated with a 20% increase in the incidence of cerebral palsy.…”