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

Pellicer, Adelina, Fernández, Ramón, Jullien, Vincent, Gleeson, Clare, Bravo, María Carmen, Ortego, Paloma López, Sánchez, Laura, Ybarra, Marta, Rojas-Anaya, Héctor, Cabañas, Fernando, Koch, Armin, Smith, Andrea, Rabe, Heike, Neocirculation Consortium, and others, (2021) Pharmacokinetic study (phase I−II) of a new dobutamine formulation in preterm infants immediately after birth. Pediatric Research, 89. pp. 981-986. ISSN 0031-3998

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Abstract

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 Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h).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:
- Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth.
- Age-related differences in drug pharmacokinetics may result in suboptimal treatments.
- The lack of formal studies in preterms results in inadequate data on efficacy and safety.
- This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation.
- There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated.
- This information is crucial for planning future trials on cardiovascular support.

Item Type: Article
Keywords: Chromatography, High Pressure Liquid, Dobutamine, Electrochemistry, Heart Diseases, Hemodynamics, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Myocardium, Patient Safety, Time Factors, Vascular Resistance
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 16 Jun 2022 15:34
Last Modified: 21 Jul 2022 16:38
URI: http://sro.sussex.ac.uk/id/eprint/106424

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