The use of multiple doses and pharmacodynamic system analysis to distinguish between dispositional delays and time-variant pharmacodynamics.

Abstract:

: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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Gastonguay MR,Schwartz SL

doi

10.1023/a:1018940122382

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

1825-8

issue

12

eissn

0724-8741

issn

1573-904X

journal_volume

11

pub_type

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