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Correction of perfusate concentration for sample removal

W L Hayton, T Chen

Journal of Pharmaceutical Sciences

|July 1, 1982

Summary

This study introduces a method to accurately measure drug concentrations in recirculating perfusate solutions. The technique corrects for drug loss during sampling, improving pharmacokinetic analysis.

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Area of Science:

Pharmacokinetics
Drug Metabolism
Analytical Chemistry

Background:

Recirculating perfusate systems are used to study drug disposition in isolated organs or tissues.
Drug concentration measurements in perfusate can be affected by repeated sampling, leading to underestimation of actual drug levels.
Accurate quantification of drug disappearance is crucial for understanding drug pharmacokinetics.

Purpose of the Study:

To develop and validate a method for correcting drug concentration measurements in recirculating perfusate systems.
To account for drug removal during serial sampling in pharmacokinetic studies.
To provide a more accurate assessment of drug disappearance rates.

Main Methods:

A mathematical correction equation was derived to adjust measured drug concentrations for sample volume.
The equation accounts for drug removed in previous samples, assuming constant total perfusate volume (VT).
The method allows for variable sampling intervals and sample volumes (VS).

Main Results:

The proposed correction method accurately recalculates drug concentrations (C'i) from serial measurements (Ci).
Errors in individual sample measurements do not propagate to subsequent corrected values.
The method is applicable even with varying time intervals and sample volumes between measurements.

Conclusions:

This validated method enables precise determination of drug disappearance rates in recirculating perfusate models.
It enhances the reliability of pharmacokinetic data derived from such experimental setups.
Potential overestimation of corrected drug concentrations may occur if drug returns to the perfusate after sampling.

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