Maternal Betamethasone for Prevention of Respiratory Distress Syndrome in Neonates: Population Pharmacokinetic and Pharmacodynamic Approach.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Adolescent
Adult
Amniotic Fluid
/ metabolism
Betamethasone
/ administration & dosage
Drug Dosage Calculations
Drug Monitoring
Female
Fetal Blood
/ metabolism
France
Gestational Age
Glucocorticoids
/ administration & dosage
Humans
Infant, Newborn
Injections, Intramuscular
Male
Maternal-Fetal Exchange
Models, Biological
Pharmacogenetics
Pharmacogenomic Variants
Polymorphism, Single Nucleotide
Pregnancy
Prospective Studies
Respiratory Distress Syndrome, Newborn
/ diagnosis
Young Adult
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
04
03
2020
accepted:
25
04
2020
pubmed:
13
5
2020
medline:
26
5
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women > 27 weeks' gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood, and amniotic fluid betamethasone time-courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood, and 26 amniotic fluid samples were described by a two-compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70 kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal-to-mother exposure ratio, the median (95% confidence interval (CI)) transplacental transfer of betamethasone was estimated to 35% (95% CI 0.11-0.67). After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent in utero below quantifiable concentrations (i.e., < 1 ng/mL): odds ratio of 1.10 (95% CI 1.01-1.19) per day increase (P < 0.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1 ng/mL without exceeding the total standard dose.
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Glucocorticoids
0
betamethasone sodium phosphate
7BK02SCL3W
Betamethasone
9842X06Q6M
betamethasone acetate
TI05AO53L7
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1026-1035Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
Roberts, D., Brown, J., Medley, N. & Dalziel, S.R. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst. Rev. 3, CD004454 (2017).
Kemp, M.W., Newnham, J.P., Challis, J.G., Jobe, A.H. & Stock, S.J. The clinical use of corticosteroids in pregnancy. Hum. Reprod. Update 22, 240-259 (2016).
Angus, D.C., Linde-Zwirble, W.T., Clermont, G., Griffin, M.F. & Clark, R.H. Epidemiology of neonatal respiratory failure in the United States: projections from California and New York. Am. J. Respir. Crit. Care Med. 164, 1154-1160 (2001).
Crowther, C.A. et al. Repeat prenatal corticosteroid prior to preterm birth: a systematic review and individual participant data meta-analysis for the PRECISE study group (prenatal repeat corticosteroid international IPD study group: assessing the effects using the best level of evidence) - study protocol. Syst. Rev. 1, 12 (2012).
Crowther, C.A., McKinlay, C.J.D., Middleton, P. & Harding, J.E. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst. Rev. 7, CD003935 (2015).
Elimian, A. et al. Antenatal corticosteroids: are incomplete courses beneficial? Obstet. Gynecol. 102, 352-355 (2003).
Kuk, J.-Y. et al. Optimal time interval between a single course of antenatal corticosteroids and delivery for reduction of respiratory distress syndrome in preterm twins. Am. J. Obstet. Gynecol. 209, 256.e1-256.e7 (2013).
Ballard, P.L., Granberg, P. & Ballard, R.A. Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. J. Clin. Invest. 56, 1548-1554 (1975).
Anderson, A.B. et al. Placental transfer and metabolism of betamethasone in human pregnancy. Obstet. Gynecol. 49, 471-474 (1977).
Petersen, M.C., Nation, R.L., Ashley, J.J. & McBride, W.G. The placental transfer of betamethasone. Eur. J. Clin. Pharmacol. 18, 245-247 (1980).
Ballabh, P. et al. Pharmacokinetics of betamethasone in twin and singleton pregnancy. Clin. Pharmacol. Ther. 71, 39-45 (2002).
Gyamfi, C. et al. The effect of plurality and obesity on betamethasone concentrations in women at risk for preterm delivery. Am. J. Obstet. Gynecol. 203, 219.e1-219.e5 (2010).
Benaboud, S. et al. Pregnancy-related effects on lamivudine pharmacokinetics in a population study with 228 women. Antimicrob. Agents Chemother. 56, 776-782 (2012).
Benaboud, S. et al. Population pharmacokinetics of nevirapine in HIV-1-infected pregnant women and their neonates. Antimicrob. Agents Chemother. 55, 331-337 (2011).
Bouazza, N. et al. Methodological approaches to evaluate fetal drug exposure. Curr. Pharm. Des. 25, 496-504 (2019).
World Health Organization (WHO). WHO Recommendations on Interventions to Improve Preterm Birth Outcomes. p. 20-28 (World Health Organization, Geneva, 2015) <http://www.ncbi.nlm.nih.gov/books/NBK321160/>.
Hoffmeyer, S. et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. 97, 3473-3478 (2000).
Extension of the SAEM algorithm to left-censored data in nonlinear mixed-effects model: Application to HIV dynamics model - ScienceDirect <https://www.sciencedirect.com/science/article/abs/pii/S0167947306001393>.
Della Torre, M., Hibbard, J.U., Jeong, H. & Fischer, J.H. Betamethasone in pregnancy: influence of maternal body weight and multiple gestation on pharmacokinetics. Am. J. Obstet. Gynecol. 203, 254.e1-254.e12 (2010).
Brendel, K., Comets, E., Laffont, C., Laveille, C. & Mentré, F. Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide. Pharm. Res. 23, 2036-2049 (2006).
Bergstrand, M., Hooker, A.C., Wallin, J.E. & Karlsson, M.O. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 13, 143-151 (2011).
Sweet, D.G. et al. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants-2013 update. Neonatology 103, 353-368 (2013).
Liggins, G.C. & Howie, R.N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 50, 515-525 (1972).
Bonanno, C. & Wapner, R.J. Antenatal corticosteroids in the management of preterm birth: are we back where we started? Obstet. Gynecol. Clin. North Am. 39, 47-63 (2012).
Halekoh, U., Højsgaard, S. & Yan, J. The R package geepack for generalized estimating equations. J. Stat. Softw. 15, 1-11 (2006).
Pan, W. Akaike's information criterion in generalized estimating equations. Biometrics 57, 120-125 (2001).
Soetaert, K. plot3D: Plotting Multi-Dimensional Data <https://CRAN.R-project.org/package=plot3D> (2019).
Salem, I.I. & Najib, N.M. Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects. Clin. Ther. 34, 214-220 (2012).
Giuffrè, M., Piro, E. & Corsello, G. Prematurity and twinning. J. Matern. Fetal Neonatal Med. 25 (suppl. 3), 6-10 (2012).
Heino, A. et al. Variations in multiple birth rates and impact on perinatal outcomes in Europe. PLoS One 11, e0149252 (2016).
Toutain, P.L. & Bousquet-Mélou, A. Plasma terminal half-life. J. Vet. Pharmacol. Ther. 27, 427-439 (2004).
Jobe, A.H. et al. Betamethasone for lung maturation: testing dose and formulation in fetal sheep. Am. J. Obstet. Gynecol. 197, 523.e1-523.e6 (2007).
Schmidt, A.F. et al. Low-dose betamethasone-acetate for fetal lung maturation in preterm sheep. Am. J. Obstet. Gynecol. 218, 132.e1-132.e9 (2018).
Loehle, M. et al. Dose-response effects of betamethasone on maturation of the fetal sheep lung. Am. J. Obstet. Gynecol. 202, 186.e1-186.e7 (2010).
Kemp, M.W. et al. The efficacy of antenatal steroid therapy is dependent on the duration of low-concentration fetal exposure: evidence from a sheep model of pregnancy. Am. J. Obstet. Gynecol. 219, 301.e1-301.e16 (2018).
Kemp, M.W. et al. The duration of fetal antenatal steroid exposure determines the durability of preterm ovine lung maturation. Am. J. Obstet. Gynecol. 222, 183.e1-183.e9 (2019).
Ballard, P.L. & Ballard, R.A. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am. J. Obstet. Gynecol. 173, 254-262 (1995).
Norman, M. et al. Association of short antenatal corticosteroid administration-to-birth intervals with survival and morbidity among very preterm infants: results from the EPICE cohort. JAMA Pediatr. 171, 678-686 (2017).
Liggins, G.C. Premature delivery of foetal lambs infused with glucocorticoids. J. Endocrinol. 45, 515-523 (1969).
Jobe, A.H. & Soll, R.F. Choice and dose of corticosteroid for antenatal treatments. Am. J. Obstet. Gynecol. 190, 878-881 (2004).
Ikegami, M. et al. Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs. Am. J. Respir. Crit. Care Med. 156, 178-184 (1997).
Johnson, J.W. et al. Long-term effects of betamethasone on fetal development. Am. J. Obstet. Gynecol. 141, 1053-1064 (1981).
Crowther, C.A. et al. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet Lond. Engl. 367, 1913-1919 (2006).
Wapner, R.J. et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am. J. Obstet. Gynecol. 195, 633-642 (2006).