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Positron emission tomography and target-controlled infusion for precise modulation of brain drug concentration
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2008 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 35, no 3, 299-303 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: There are several instances when it is desirable to control brain concentration of pharmaceuticals, e.g., to modulate the concentration of anesthetic agents to different desired levels fitting to different needs during the course of surgery. This has so far only been possible using indirect estimates of drug concentration such as assuming constant relation between tissue and blood including extrapolations from animals. Methods: A system for controlling target tissue concentration (UIPump) was used to regulate whole-brain concentrations of a central benzodiazepine receptor antagonist at therapeutic levels with input from brain kinetics as determined with PET. The system was tested by using pharmacological doses of flumazenil mixed with tracer amounts of [C-11]flumazenil. Flumazenil was used as a model compound for anesthesia. An infusion scheme to produce three different steady-state levels in sequence was designed based on kinetic curves obtained after bolus injection. The subjects (Sprague-Dawley rats, n = 6) were monitored in a microPET scanner during the whole experiment to verify resulting brain kinetic curves. Results: A steady-state brain concentration was rapidly achieved corresponding to a whole-brain concentration of 118 +/- 6 ng/ml. As the infusion rate decreased to lower the exposure by a factor of 2, the brain concentration decreased to 56 +/- 4 ng/ml. A third increased steady-state level of anesthesia corresponding to a whole-brain concentration of 107 +/- 7 ng/ml was rapidly achieved. Conclusion: The experimental setup with computerized pump infusion and PET supervision enables accurate setting of target tissue drug concentration.

Place, publisher, year, edition, pages
2008. Vol. 35, no 3, 299-303 p.
Keyword [en]
PET, TCI, CCIP, flumazenil, brain distribution
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-110446DOI: 10.1016/j.nucmedbio.2007.12.003ISI: 000254592100006PubMedID: 18355685OAI: oai:DiVA.org:uu-110446DiVA: diva2:277174
Available from: 2009-11-16 Created: 2009-11-16 Last updated: 2017-12-12Bibliographically approved

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Eriksson, Olof

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