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

Pellicer, Adelina; Fernández, R. Hernando; 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

doi:10.1038/s41390-020-1009-0

Cited by 6 publications

(6 citation statements)

References 24 publications

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“…Dobutamine could be more effective than dopamine in preterm infants accompanied by low systemic blood flow due to immature myocardiac contractility during the early neonatal period because dobutamine has been shown to be more effective than dopamine at increasing systemic blood flow [19]. However, dobutamine has a weak effect on increasing blood pressure, which is the major circulatory parameter in NICUs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial

Ishiguro,

Kabe

2023

Neonatology

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Introduction: This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. Methods: This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. Results: Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). Conclusions: Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation.

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Section: Discussionmentioning

confidence: 99%

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial

Ishiguro,

Kabe

2023

Neonatology

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“…Following continuous intravenous infusion, the distribution half-life is 3.01 min, the elimination half-life is 25.8 min, and the distribution volume is 1.13 L/kg, suggesting that dobutamine is rapidly distributed, is rapidly eliminated, and the distribution volume is similar to the water volume [20]. The treatment on infants and children with dobutamine has been studied [21][22][23][24][25][26]. Dobutamine is used in the treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in preterm infants [21].…”

Section: Discussionmentioning

confidence: 99%

“…The treatment on infants and children with dobutamine has been studied [21][22][23][24][25][26]. Dobutamine is used in the treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in preterm infants [21]. The prevalence of dopamine or dobutamine use is 4.9% in preterm infants and 21.1% in very-low-birth-weight infants [22].…”

Section: Discussionmentioning

confidence: 99%

Clinical Pharmacology Of Dobutamine In Infants And Children

Maria Pacifici

2022

CRN

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Dobutamine resembles dopamine structurally but possess a bulky aromatic substituent on the amino group. The pharmacological effects of dobutamine are due to direct interaction with α and β receptors. Dobutamine possess a centre of asymmetry, the (-) isomer of dobutamine is a potent α1 agonist and can cause marked pressor response. In contrast, (+) dobutamine is a potent α1 receptor antagonist which can block the effect of (-) dobutamine. Both isomers are full agonist at β receptors; the (+) isomer is a more potent β agonist than the (-) isomer by about 10-fold. Dobutamine is indicated for the short-term treatment of cardiac decompensation that may occur after cardiac surgery and dobutamine is used in the treatment of hypotension especially if related to myocardial dysfunction. Dobutamine is administered by continuous intravenous infusion and the initial dose is 5 µg/kg per min in infants and children. Some authors stated that dopamine is more effective than dobutamine in increasing blood pressure whereas other authors observed that dobutamine and dopamine produce similar pressure response. Dobutamine is methylated and is also conjugated with glucuronic acid. The elimination half-life of dobutamine is 25.6 min in infants and children but it ranges in a wide interval. The treatment of infants and children with dobutamine has been extensively studied and some authors observed that dobutamine increase the blood pressure and decreases vascular resistance. The aim of this study is to review the dobutamine dosing, effects, metabolism, pharmacokinetics, and treatment.

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“…Two recent studies assessed the pharmacokinetics and/or pharmacodynamics of DOB during the transitional period. It was found that the pharmacokinetics followed a onecompartmental linear model and that clearance correlated with postmenstrual age and birth weight [14,121]. Moreover, plasma levels were related with hemodynamic parameters, including right ventricular output, left ventricular ejection fraction (linear model), left ventricular output, HR, and mean AP (sigmoidal E max model) [63,64,121].…”

Section: Dobutaminementioning

confidence: 98%

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication

Agakidou,

Chatziioannidis,

Kontou

et al. 2024

Children

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Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed.

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

Cited by 6 publications

References 24 publications

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial

Clinical Pharmacology Of Dobutamine In Infants And Children

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication

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