A Literature Review of the Pharmacokinetics and Pharmacodynamics of Dobutamine in Neonates
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Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review of pharmacokinetic and pharmacodynamic data for dobutamine in the pediatric population. Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria. Where possible, results for the pharmacodynamic and pharmacokinetic effect of dobutamine were reported as pooled data. Forty-six papers met the inclusion criteria. With regard to pharmacodynamic data a number of studies reported significant increases in a number of clinical parameters such as heart rate, blood pressure, cardiac output across a wide range of pediatric populations. With regard to pharmacokinetic data studies reported that the infusion rate was positively correlated to plasma dobutamine concentration. There was great variability with regard to dobutamine clearance between individuals and as to whether it followed first- or zero-order elimination kinetics. While the pharmacodynamic effects of dobutamine appear to reflect the pharmacological profile of the drug, the pharmacokinetic data are difficult to interpret due to inhomogeneity between study populations ages, comorbidities, dobutamine dosages and methodologies. High-quality prospective pharmacokinetic and pharmacodynamic data especially in newborns are urgently required prior to a large randomized study.
KeywordsDobutamine Neonate Hypotension Pediatric Pharmacodynamic Pharmacokinetic
A special thanks to Tom Roper and Sarah Butler, Clinical librarians at The Brighton and Sussex University Hospitals NHS Trust, for their help with searching strategies for this review. This literature review will be presented to the European Medicines Agency as part of a Pediatric Investigations Plan for the Neo-Circulation Project. The members of the consortium are outlined below: Chief Investigator: Adelina Pellicer, Madrid, Spain. Principal Project Coordinator: Heike Rabe, Brighton, UK. Local Investigators: Philip Amess, Neil Aiton, David Crook, Ramon Fernandez, Liam Mahoney, Heike Rabe, Hector Rojas-Anaya, Brighton, UK; Vincent Jullien, Thomas Le Saux, Gerard Pons, Paris, France; Frank Biertz, Wolfgang Büter, Armin Koch, Hannover, Germany; Victoria Mielgo, Adolf Valls-i-Soler (in memoriam), Bizkaia, Spain; Wolfgang Göpel, Christoph Härtel, Lübeck, Germany; Haris Kotidis, Mark Turner, Michael Weindling, Liverpool, UK; Claudia Roll, Datteln, Germany; Maria Carmen Bravo, Fernando Cabanas, Madrid, Spain; Simon Bryson, Chesire, UK; Alexandrina Tatu, Adrian Toma, Bucharest, Romania; Gabriela Zaharie, Cluj-Napoca , Romania; Géza Bokodi, Miklós Szabó, Budapest, Hungary; Tibor Ertl, Simone Funke, Pécs, Hungary; Ebru Ergenekon, Kivilcim Gücüyener, Şebnem Soysal, Ankara, Turkey; Christiane Dammann, Olaf Dammann, Jennifer Lee, Boston, US; Neo-Circulation Expert Advisory Board: Tonse N. K. Raju, Bethesda, USA; Nicholas Evans, Sydney, Australia; Stephanie Läer, Düsseldorf, Germany; Silke Mader, Karlsfeld, Germany; Monika Seibert-Grafe, Mainz, Germany. Neo-Circulation Ethics Advisory and Data Monitoring Board: Gorm Greisen, Copenhagen, Denmark; Lena Hellström-Westas, Uppsala, Sweden; Josef Högel, Ulm, Germany.
Conflict of interest
The authors declare that they have no conflict of interest.
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