Abstract
Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population.
Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days.
Results: There was a strong relationship between clearance (4.96 ml·min−1·kg−1) and gestational age (r=0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml·min−1·kg−1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l·kg−1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects.
Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.
Article PDF
Similar content being viewed by others
References
Avery GB, Fletcher AB, Kaplan M, Brudno DS (1985) Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia. Pediatrics 75:106–111
Kazzi NJ, Brans YW, Poland RL (1990) Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation. Pediatrics 86:722–727
Cummings JJ, D'Eugenio DB, Gross SJ (1989) A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med 320:1505–1510
Harkavy KL, Scanlon JW, Chowdhry PK, Grylack LJ (1989) Dexamethasone therapy for chronic lung disease in ventilatorand oxygen-dependent infants: A controlled trial. J Pediatr 115:979–983
Ohlsson A, Calvert SA, Hosking M, Shennan AT (1989) Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilatory-dependent chronic lung disease. Ped Res 25:225A
Yeh TF, Torre JA, Rastofi A, Anyebuno MA, Pildes RS (1990) Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: A double-blind, controlled study. J Pediatr 117:273–282
Collaborative Dexamethasone Trial Group (1991) Dexamethasone therapy in neonatal chronic lung disease: An international placebo-controlled trial. Pediatrics 88:421–427
Ariagno RL, Sweeney TJ, Baldwin RB, Inguillo D, Martin D (1987) Dexamethasone effects on lung function in 3 week old ventilator dependent preterm infants. Am Rev Resp Dis 135:A125
Ferrara TB, Couser RJ, Hoekstra RE (1989) Side effects and long-term follow-up of corticosteroid therapy in very low birthweight infants with bronchopulmonary dysplasia. J Perinatol 10:137–142
Wilson DM, Baldwin RB, Ariagno RL (1988) A randomized, placebo-controlled trial of effects of dexamethasone on hypothalamic-pituitary-adrenal axis in preterm infants. J Pediatr 113:764–768
Cronin CMG, Dean H, MacDonald NT, Seshia MMK (1993) Basal and post-ACTH cortisol levels in preterm infants following treatment with dexamethasone. Clin Invest Med 16:8–14
Alkalay AL, Pomerance JJ, Puri AR, et al (1990) Hypothalamic-pituitary-adrenal axis function in very low birth-weight infants treated with dexamethasone. Pediatrics 86:204–210
Rizvi ZB, Aniol HS, Myers TF, Zeller WP, Fisher SG, Anderson CL (1992) Effects of dexamethasone on the hypothalamic-pituitary-adrenal axis in preterm infants. J Pediatr 120:961–965
Sauder SE, Powers WF, Wise JE (1987) Suppression of the pituitary-adrenal axis in very low birth weight infants after dexamethasone therapy for bronchopulmonary dysplasia. Clin Res 35:913A
Ng PC, Blackburn ME, Brownlee KG, Buckler JMH, Dear PRF (1989) Adrenal response in very low birthweight babies after dexamethasone treatment for bronchopulmonary dysplasia. Arch Dis Child 64:1721–1726
MacDonald PD, Galea P, Alroomi LG (1990) A catabolic state in dexamethasone treatment of bronchopulmonary dysplasia. Arch Dis Child 65:560–561
Brownlee KG, Ng PC, Henderson MJ, Smith M, Green JH, Dear PRF (1992) Catabolic effect of dexamethasone in the preterm baby. Arch Dis Child 67:1–4
Williams AF, Jones M (1992) Dexamethasone increases plasma amino acid concentrations in bronchopulmonary dysplasia. Arch Dis Child 67:5–9
Hochhaus G, Hochhaus R, Werber G, Derendorf H (1992) A selective HPLC/RIA for dexamethasone and its prodrug dexamethasone-21-sulphobenzoate sodium in biologic fluids. Biomed Chromatogr 6:283–286
Morselli PL, Morselli RF, Bossi L (1980) Clinical pharmacokinetics in newborns and infants. Clin Pharmacokinet 5:485–527
Tsuei SE, Moore RG, Ashley JJ, McBride WG (1979) Disposition synthetic glucocorticoids. I. Pharmacokinetics of dexamethasone in healthy adults. J Pharmacokinet Biopharm 7:249–264
Eadie MJ, Brophy TR, Ohlrich G, Tyrer JH (1984) Dexamethasone: pharmacokinetics in neurological patients. Clin Exp Neurol 20:107–118
Charles B, Schild P, Steer P, Cartwright D, Donovan T (1993) Pharmacokinetics of dexamethasone following single-dose intravenous administration to extremely low birth weight infants. Dev Pharmacol Ther 20:205–210
Richter O, Reinhardt D, Becker B (1983) Pharmacokinetics of dexamethasone in children. Pediatr Pharmacol 3:329–337
Mammel MC, Johnson DE, Green T, Thompson TR (1983) Controlled trial of dexamethasone in infants with bronchopulmonary dysplasia. Lancet I:1356–1357
Georgieff MK, Mammel MC, Mills MM, Gunter EW, Johnson DE, Thompson TR (1989) Effect of postnatal steroid administration on serum vitamin A concentrations in newborn infants with respiratory compromise. J Pediatr 114:301–304
Britton MG, Collins JV, Brown D, Fairhurst NPA, Lambert RG (1976) High-dose corticosteroids in severe acute asthma. Br Med J 2:73
Ng PC (1993) The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. Arch Dis Child 68:330–336
Meikle AW, Clarke DH, Tyler FH (1976) Cushing syndrome from low doses of dexamethasone. JAMA 235: 1592–1593
Kozower M, Veatch L, Kaplan MM (1974) Decreased clearance of prednisolone, a factor in the development of corticosteroid side effects. J Clin Endocrinol Metab 38:407–411
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lugo, R.A., Nahata, M.C., Menke, J.A. et al. Pharmacokinetics of dexamethasone in premature neonates. Eur J Clin Pharmacol 49, 477–483 (1996). https://doi.org/10.1007/BF00195934
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00195934