Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle
Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challeng...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2013-08-01
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| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/117.pdf |
| _version_ | 1797424993793998848 |
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| author | Kevin J. Black Jonathan M. Koller Brad D. Miller |
| author_facet | Kevin J. Black Jonathan M. Koller Brad D. Miller |
| author_sort | Kevin J. Black |
| collection | DOAJ |
| description | Pharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, rapid quantitative pharmacodynamic imaging reliably estimates EC50 from the simulated data, except when noise overwhelms the drug effect or when the effect occurs only at high doses. In preliminary fMRI studies of primate brain using a dopamine agonist, the observed noise level is modest compared with observed drug effects, and a quantitative EC50 can be obtained from some regional time-signal curves. Taken together, these results suggest that research and clinical applications for rapid quantitative pharmacodynamic imaging are realistic. |
| first_indexed | 2024-03-09T08:09:36Z |
| format | Article |
| id | doaj.art-8a23aaf86ab84e0da0b61088b6b05304 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:09:36Z |
| publishDate | 2013-08-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-8a23aaf86ab84e0da0b61088b6b053042023-12-02T23:31:54ZengPeerJ Inc.PeerJ2167-83592013-08-011e11710.7717/peerj.117117Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principleKevin J. Black0Jonathan M. Koller1Brad D. Miller2Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USAPharmacological challenge imaging has mapped, but rarely quantified, the sensitivity of a biological system to a given drug. We describe a novel method called rapid quantitative pharmacodynamic imaging. This method combines pharmacokinetic-pharmacodynamic modeling, repeated small doses of a challenge drug over a short time scale, and functional imaging to rapidly provide quantitative estimates of drug sensitivity including EC50 (the concentration of drug that produces half the maximum possible effect). We first test the method with simulated data, assuming a typical sigmoidal dose-response curve and assuming imperfect imaging that includes artifactual baseline signal drift and random error. With these few assumptions, rapid quantitative pharmacodynamic imaging reliably estimates EC50 from the simulated data, except when noise overwhelms the drug effect or when the effect occurs only at high doses. In preliminary fMRI studies of primate brain using a dopamine agonist, the observed noise level is modest compared with observed drug effects, and a quantitative EC50 can be obtained from some regional time-signal curves. Taken together, these results suggest that research and clinical applications for rapid quantitative pharmacodynamic imaging are realistic.https://peerj.com/articles/117.pdfPharmacodynamicsNeuroimagingfMRIPharmacokinetic-pharmacodynamic modelingDrug developmentDose-finding |
| spellingShingle | Kevin J. Black Jonathan M. Koller Brad D. Miller Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle PeerJ Pharmacodynamics Neuroimaging fMRI Pharmacokinetic-pharmacodynamic modeling Drug development Dose-finding |
| title | Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle |
| title_full | Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle |
| title_fullStr | Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle |
| title_full_unstemmed | Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle |
| title_short | Rapid quantitative pharmacodynamic imaging by a novel method: theory, simulation testing and proof of principle |
| title_sort | rapid quantitative pharmacodynamic imaging by a novel method theory simulation testing and proof of principle |
| topic | Pharmacodynamics Neuroimaging fMRI Pharmacokinetic-pharmacodynamic modeling Drug development Dose-finding |
| url | https://peerj.com/articles/117.pdf |
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