Use of metzler's NONLIN program for fitting discontinuous absorption profiles

Area of Science:

• Pharmacokinetics
• Mathematical Modeling
• Computational Chemistry

Background:

• Integral hybrid flow/compartmental models (HFCM) are commonly used for fitting discontinuous drug absorption profiles.
• HFCM integral equations can present challenges, including the potential for negative absorption times, which are physically unrealistic.

Purpose of the Study:

• To present an alternative method using differential equations to fit discontinuous absorption profiles.
• To address limitations of HFCM integral equations, specifically the issue of negative absorption times.

Main Methods:

• A system of sequential differential equations was developed to describe absorption profiles from time zero to infinity.
• The NONLIN program was utilized in differential equation mode for fitting absorption data.
• The method was applied to analyze absorption profiles of buformin, sulfisoxazole, and griseofulvin.

Main Results:

• The differential equation method provided good fits for unusually shaped absorption profiles.
• Parameter estimates and sum of squared deviations from NONLIN were comparable to those from the FITS12 program using HFCM equations.
• The differential equation approach successfully avoided the problem of negative absorption times.

Conclusions:

• Differential equations offer a robust alternative to HFCM integral equations for pharmacokinetic modeling.
• This method enhances the reliability of absorption profile analysis by eliminating non-physical results.
• The differential equation approach is effective for modeling complex, multi-step drug absorption processes.