Maturation, pharmacogenomics and metabolomics as factors determining pharmacokinetic  and pharmacodynamics profile of alpha-agonist  in pediatric intensive care unit patients

Joanna Bartkowiak-Wieczorek; Justyna Mocarska; Alicja Bartkowska-Śniatkowska; Jan Matysiak; Agnieszka Klupczyńska; Zenon J. Kokot; Paweł Wiczling; Edmund Grześkowiak; Agnieszka Bienert

doi:10.20883/jms.2016.147

Authors

Joanna Bartkowiak-Wieczorek Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland
Justyna Mocarska Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland
Alicja Bartkowska-Śniatkowska Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland
Jan Matysiak Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland
Agnieszka Klupczyńska Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland
Zenon J. Kokot Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland
Paweł Wiczling Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland
Edmund Grześkowiak Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland
Agnieszka Bienert Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland

DOI:

https://doi.org/10.20883/jms.2016.147

Keywords:

pharmacogenomics, metabolomics, pharmacokinetic, pharmacodynamics, dexmedetomidine, clonidine

Abstract

Research Project Objectives. Project entitled “Maturation, pharmacogenomics, and metabolomics as factors determining pharmacokinetic and pharmacodynamic profile of alpha-agonist in pediatric intensive care unit patients” was founded by the Polish National Science Center (NCN) under project number: 2015/17/B/NZ7/03032. The duration of the grant is 36 months, and the total grant value is 688800 PLN. The project is run by the Medical University of Gdansk and Poznan University of Medical Sciences. The aim of this grant is to examine the influence of maturation, pharmacogenetics, metabolomics and physiological (or pathophysiological) status of the patients on the pharmacokinetics and pharmacodynamics (PK/PD) of ?2-adrenergic drugs (dexmedetomidine and clonidine) in pediatric population. The project was proposed to explain the unusual PK of dexmedetomidine reported in literature and in our preliminary experiments, in which a two-fold increase in dexmedetomidine clearance was observed during prolonged (lasting more than 24 hr) infusions in the intensive care unit patients.
General information. Project entitled “Maturation, pharmacogenomics, and metabolomics as factors determining pharmacokinetic and pharmacodynamics profile of alpha-agonist in pediatric intensive care unit patients” was founded by the Polish National Science Center (NCN) under project number: 2015/17/B/NZ7/03032. The duration of the grant is 36 months, from 2016-04-27 to 2019-04-26 and the total grant value is 688800 PLN. The project is run by the Medical University of Gdansk and Poznan University of Medical Sciences. The research group consists of: principal investigator dr hab. Paweł Wiczling and co-investigators: dr hab. Agnieszka Bienert, dr Alicja Bartkowska-Śniatkowska, dr Joanna Bartkowiak-Wieczorek, mgr Justyna Mocarska, prof. Edmund Grześkowiak, dr Jan Matysiak, mgr Agnieszka Klupczyńska, dr Danuta Siluk, mgr Agnieszka Borsuk and prof. dr hab. Zenon J. Kokot. The Ethical Committee permission number is 261/15.

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References

Clayton TA, Lindon JC, Cloarec O, Antti H, Charuel C, Hanton G, Provost JP, Le Net JL, Baker D, Walley RJ, Everett JR, Nicholson JK. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 2006 Apr;440(7087):1073–1077.

Nebert DW, Vesell ES. Advances in pharmacogenomics and individualized drug therapy: exciting challenges that lie ahead. Eur J Pharmacol. 2004;500(1–3):267–280.

Iirola T, Ihmsen H, Laitio R, Kentala E, Aantaa R, Kurvinen JP, Scheinin M, Schwilden H, Schüttler J, Olkkola KT. Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients. Br J Anaesth. 2012 Mar;108(3):460–468.

Struck W, Wiczling P, Waszczuk-Jankowska M, Kaliszan R, Markuszewski MJ. New supervised alignment method as a preprocessing tool for chromatographic data in metabolomic studies. J Chromatogr A. 2012 Sep;1256:150–159.

Struck W, Siluk D, Yumba-Mpanga A, Markuszewski M, Kaliszan R, Markuszewski MJ. Liquid chromatography tandem mass spectrometry study of urinary nucleosides as potential cancer markers. J Chromatogr A. 2013 Mar;1283:122–131.

Struck W, Waszczuk-Jankowska M, Kaliszan R, Markuszewski MJ. The state-of-the-art determination of urinary nucleosides using chromatographic techniques "hyphenated" with advanced bioinformatic methods. Anal Bioanal Chem. 2011 Oct;401(7):2039–2050.

NONMEM Users Guides. In: Beal SL, Sheiner LB, editors. Maryland: Icon Development Solutions; 1989–1998.

Bienert A, Płotek W, Wiczling P, Warzybok J, Borowska K, Buda K, Kulińska K, Billert H, Kaliszan R, Grześkowiak E. The influence of age and dosage on the pharmacodynamics of dexmedetomidine in rabbits. JMS. 2014;83(2):108–115.

Carrasco G. Instruments for monitoring intensive care unit sedation. Crit Care. 2000;4:217–225.