Drug absorption evaluation in the presence of changes in clearance: an algorithm and computer program for...

Area of Science:

• Pharmacokinetics
• Drug Metabolism and Disposition

Background:

• Standard drug absorption evaluation assumes constant drug disposition between administrations, which is often violated.
• This violation leads to significant errors in pharmacokinetic calculations.
• Accurate assessment of drug absorption is crucial for effective therapeutic dosing.

Purpose of the Study:

• To present a novel deconvolution method that precisely corrects for alterations in drug clearance during pharmacokinetic studies.
• To improve the accuracy of drug absorption calculations when drug disposition changes between administrations.
• To provide a practical tool for pharmacokinetic analysis.

Main Methods:

• A model-independent disposition decomposition-recomposition technique is employed.
• The distribution function is derived from intravenous administration data.
• The method reconstructs the perturbed disposition function using the distribution function and altered elimination kinetics.
• The perturbed absorption response is deconvolved using the corresponding perturbed disposition function.

Main Results:

• The novel method accurately compensates for changes in drug clearance.
• Perturbed clearance can be determined from the terminal disposition phase after obtaining the distribution function.
• The algorithm and computer program DCONB were developed and validated using human cimetidine data.
• DCONB implementation is straightforward, requiring standard pharmacokinetic data fitting techniques.

Conclusions:

• The presented deconvolution method effectively addresses the challenge of changing drug clearance in pharmacokinetic assessments.
• The DCONB program offers a simple yet powerful tool for accurate drug absorption and disposition analysis.
• This approach enhances the reliability of pharmacokinetic calculations in clinical practice.