The use of multiple doses and pharmacodynamic system analysis to distinguish between dispositional delays and time-variant pharmacodynamics
Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitiza...
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| Veröffentlicht in: | Pharmaceutical research 1994-12, Vol.11 (12), p.1825-1828 |
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| container_title | Pharmaceutical research |
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| creator | GASTONGUAY, M. R SCHWARTZ, S. L |
| description | Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. However, with single dosing, hysteresis that results from a time-variant biophase concentration-effect relationship cannot be distinguished from hysteresis caused by dispositional delays. This can lead to the inappropriate minimization of hysteresis. As an approach to this problem, simulated and real kinetic-dynamic data were analyzed with the pharmacodynamic system analysis program ATTRACT. The use of a multiple dosing regimen and this hysteresis minimization algorithm resulted in a simple diagnostic test to distinguish between dispositional effects of acute tolerance and sensitization. |
| doi_str_mv | 10.1023/A:1018940122382 |
| format | Article |
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L</creatorcontrib><title>The use of multiple doses and pharmacodynamic system analysis to distinguish between dispositional delays and time-variant pharmacodynamics</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. However, with single dosing, hysteresis that results from a time-variant biophase concentration-effect relationship cannot be distinguished from hysteresis caused by dispositional delays. This can lead to the inappropriate minimization of hysteresis. As an approach to this problem, simulated and real kinetic-dynamic data were analyzed with the pharmacodynamic system analysis program ATTRACT. The use of a multiple dosing regimen and this hysteresis minimization algorithm resulted in a simple diagnostic test to distinguish between dispositional effects of acute tolerance and sensitization.</description><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Tolerance</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Pharmacokinetics</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. 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L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c281t-3de9679b35a1e66ca1e206dcacdaaa6ceeb1034962aae37462ea4d449b77417e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Tolerance</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Pharmacokinetics</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GASTONGUAY, M. R</creatorcontrib><creatorcontrib>SCHWARTZ, S. 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| ispartof | Pharmaceutical research, 1994-12, Vol.11 (12), p.1825-1828 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Biological and medical sciences Dose-Response Relationship, Drug Drug Tolerance General pharmacology Humans Medical sciences Models, Biological Pharmacokinetics Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments |
| title | The use of multiple doses and pharmacodynamic system analysis to distinguish between dispositional delays and time-variant pharmacodynamics |
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