The extension grade: a model-unspecific rate characteristic derived from steady-state plasma level fluctuations

Area of Science:

• Pharmacokinetics
• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Assessing the rate of drug bioavailability is crucial for pharmaceutical dosage forms, especially sustained-release preparations.
• Existing methods may not fully account for interindividual pharmacokinetic variability.
• A need exists for a comprehensive metric to characterize drug input kinetics.

Purpose of the Study:

• To introduce and define the extension grade (EG) as a novel metric for quantifying the rate aspect of bioavailability.
• To demonstrate that EG is independent of specific pharmacokinetic models and statistical moment analysis.
• To show that EG accounts for interindividual differences in disposition kinetics.

Main Methods:

• The extension grade (EG) is computed from steady-state data comparing a test product to a reference.
• EG can be calculated using steady-state plasma drug concentrations and urinary excretion rates.
• Corresponding profiles from single-dose administrations can also be utilized for EG determination.

Main Results:

• The extension grade (EG) quantifies the overall drug input, encompassing both release and absorption kinetics.
• EG ranges from 0 to 1, similar to the extent of bioavailability (F).
• The calculation of EG is straightforward and can be implemented through specific experimental designs.

Conclusions:

• The extension grade (EG) provides a robust measure for the rate of bioavailability in pharmaceutical formulations.
• EG offers a model-independent approach that inherently considers interindividual pharmacokinetic variations.
• The simplicity and versatility of EG facilitate its practical application in drug development and evaluation.