Pharmacokinetic study (phase I-II) of a new dobutamine formulation in preterm infants immediately after birth

Pellicer A., Fernandez R., Jullien V., Gleeson C., Bravo M. C., Ortego P. L., ...More

PEDIATRIC RESEARCH, vol.89, no.4, pp.981-986, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 89 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.1038/s41390-020-1009-0
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.981-986
  • Gazi University Affiliated: Yes


Background Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. Methods Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. Results Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. Conclusions The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. Impact