Pharmacokinetics of dexamethasone in premature neonates

Ra, Lugo; Mc, Nahata; Ja, Menke; Re, McClead

doi:10.1007/bf00195934

Cited by 30 publications

(15 citation statements)

References 25 publications

(41 reference statements)

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“…[19][20][21] Because of the concerns about side effects, routine use of postnatal DX is not indicated. 22,23 Watterberg et al 24 demonstrated a significant increase in survival without BPD in a pilot study using low-dose hydrocortisone (HC; ie, dosage approaching cortisol levels reached in stress) given shortly after birth.Based on the promising early results of the pilot study by others, 24 we conducted a randomized, placebo-controlled trial of early HC treatment beginning within 36 hours after birth. The aims were to investigate whether HC treatment improves the survival without BPD in VLBW infants and whether pretreatment serum cortisol concentrations predict the therapeutic response.…”

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confidence: 99%

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Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants

Peltoniemi¹,

Kari²,

Heinonen³

et al. 2005

The Journal of Pediatrics

126

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confidence: 99%

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confidence: 99%

Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants

Peltoniemi¹,

Kari²,

Heinonen³

et al. 2005

The Journal of Pediatrics

126

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“…Under the same experimental conditions, we previously found that this level of IL-10 or DEX produced a marked inhibition of LPS-induced IL-8 release from PMNs of the newborn (10, 14). Furthermore, DEX at 10 −8 M is in the therapeutic range of DEX levels measured in plasma from infants treated for BPD (15, 16). In the present study, we measured the pro-inflammatory mediators TNFα and IL-1β, as well as the anti-inflammatory mediators IL-4 and IL-1 receptor antagonist (IL-1ra), using commercially available ELISA kits (R&D Systems).…”

Section: Methodsmentioning

confidence: 89%

“…The aim of the present study was to compare the effect of IL-10 versus DEX on important PMN innate immune functions of the newborn. The plasma levels of DEX known to be associated with a reduction in BPD have been previously described and are in the range of 10 −8 M (15, 16). In previous work, we demonstrated that endotoxin-stimulated release of IL-8 from PMNs of the newborn was markedly inhibited by equimolar levels (10 −8 M) of DEX or IL-10 (10).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 Versus Dexamethasone: Effects on Polymorphonuclear Leukocyte Functions of the Newborn

et al. 2009

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Interleukin-10 (IL-10), an anti-inflammatory cytokine, may have therapeutic potential in the fetal inflammatory response syndrome and its sequelae such as bronchopulmonary dysplasia (BPD). Our aim was to compare the effects of IL-10 versus dexamethasone (DEX) on important PMN functions of the newborn. PMNs were isolated into culture medium from cord blood after elective cesarean section deliveries. IL-10 and DEX were compared on an equimolar basis corresponding to previously measured plasma levels of DEX from infants treated for BPD. The endotoxin (LPS)-stimulated release of the pro-inflammatory cytokines, tumor necrosis factor (TNFα) and IL-1β, were markedly inhibited equally by IL-10 and DEX; the anti-inflammatory cytokine IL-4 was not released and IL-1 receptor antagonist (IL-1ra) was released less with DEX compared to IL-10. PMNs exposed to LPS, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), or S. aureus did not show a significant difference between control, DEX and IL-10 for apoptosis, respiratory burst, phagocytosis or killing respectively. Chemotaxis to fMLP or IL-8 was unaffected by DEX or IL-10. The principal effects of both IL-10 and DEX, on the PMN functions studied, are related to the control of pro- and anti-inflammatory cytokine release.

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“…However, this dose resulted in short term adverse effects, such as hypertension and hyperglycemia, similar to those observed with higher doses (1,2). The limited pharmacokinetic data available indicate that the half-life of dexamethasone is prolonged in ELBW infants compared to children and adults (24,25). Accumulation of the drug may have contributed to high levels of dexamethasone that increased the rate of early adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Death or Neurodevelopmental Impairment at 18 to 22 Months Corrected Age in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants

Stark

Carlo

Vohr

et al. 2014

The Journal of Pediatrics

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Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. Methods Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment. Results Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.

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Pharmacokinetics of dexamethasone in premature neonates

Abstract: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.

Cited by 30 publications

References 25 publications

Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants

Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants

Interleukin-10 Versus Dexamethasone: Effects on Polymorphonuclear Leukocyte Functions of the Newborn

Death or Neurodevelopmental Impairment at 18 to 22 Months Corrected Age in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants

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