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Neuropharmacokineti...
Neuropharmacokinetic visualization of regional and subregional unbound antipsychotic drug transport across the blood-brain barrier.
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- Luptáková, Dominika (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medical Mass Spectrometry
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- Vallianatou, Theodosia (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Medical Mass Spectrometry
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical Mass Spectrometry
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- Shariatgorji, Reza (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical Mass Spectrometry
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- Hammarlund-Udenaes, Margareta (author)
- Uppsala universitet,Institutionen för farmaci,Translational PKPD (tPKPD)
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- Loryan, Irena, Associate Professor (Docent), 1977- (author)
- Uppsala universitet,Institutionen för farmaci,Translational PKPD (tPKPD)
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- Andrén, Per E., Professor, 1957- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Medical Mass Spectrometry
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(creator_code:org_t)
- 2021-09-03
- 2021
- English.
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26, s. 7732-7745
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- Comprehensive determination of the extent of drug transport across the region-specific blood-brain barrier (BBB) is a major challenge in preclinical studies. Multiple approaches are needed to determine the regional free (unbound) drug concentration at which a drug engages with its therapeutic target. We present an approach that merges in vivo and in vitro neuropharmacokinetic investigations with mass spectrometry imaging to quantify and visualize both the extent of unbound drug BBB transport and the post-BBB cerebral distribution of drugs at regional and subregional levels. Direct imaging of the antipsychotic drugs risperidone, clozapine, and olanzapine using this approach enabled differentiation of regional and subregional BBB transport characteristics at 20-µm resolution in small brain regions, which could not be achieved by other means. Our approach allows investigation of heterogeneity in BBB transport and presents new possibilities for molecular psychiatrists by facilitating interpretation of regional target-site exposure results and decision-making.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- blood-brain barrier
- neuropharmacokinetics
- mass specrtometry imaging
- psychiatry
- unbound drug
- Pharmacokinetics and Drug Therapy
- Farmakokinetik och läkemedelsterapi
Publication and Content Type
- ref (subject category)
- art (subject category)
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