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Probe calibration in transient microdialysis in vivo
P M Bungay1, R L Dedrick, E Fox
1Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, Maryland 20892, USA. bungayp@mail.nih.gov
Pharmaceutical Research
|July 10, 2001
Summary
Calibration of microdialysis probes in vivo during changing analyte concentrations is complex. This study shows that area-under-the-curve integrals offer a way to determine calibration factors in linear systems under non-steady-state conditions.
Area of Science:
- Pharmacokinetics
- Biomedical Engineering
- Analytical Chemistry
Background:
- In vivo microdialysis is crucial for pharmacokinetic studies.
- Accurate calibration of microdialysis probes is essential for reliable data.
- Traditional calibration methods assume steady-state conditions, which are often not met.
Purpose of the Study:
- To investigate the theoretical basis for calibrating microdialysis probes in vivo under dynamic extracellular analyte concentrations.
- To address the challenges of probe calibration in pharmacokinetic experiments with time-varying analyte levels.
Main Methods:
- Utilized the MICRODIAL software package for simulations.
- Modeled microdialysis under transient conditions with linear concentration dependence.
- Examined the influence of mass transfer and analyte clearance on calibration factors.
Main Results:
- Calibration factor (extraction fraction, Ed) shows a mass transfer transient due to developing concentration profiles.
- Analyte clearance from extracellular fluid (ECF) impacts the speed of reaching steady-state and the steady-state calibration factor (Ess(d)).
- In linear, transient systems, the area-under-the-curve (AUC 0-infinity) of ECF concentration is proportional to the dialysate concentration integral, with Ess(d) as the constant.
Conclusions:
- Microdialysis probe calibration in solid tissues is limited under non-steady-state conditions.
- AUC integrals for linear systems can be determined using continuous sampling and steady-state calibration.
- This provides a potential method for calibrating probes in dynamic pharmacokinetic studies.
