Cefixime absorption kinetics after oral administration to humans

Area of Science:

• Pharmacokinetics
• Drug Absorption
• Clinical Pharmacology

Background:

• Understanding drug absorption is crucial for optimizing therapeutic efficacy.
• Cefixime (CFX) is a widely used oral antibiotic.
• Accurate pharmacokinetic modeling aids in predicting drug behavior in the body.

Purpose of the Study:

• To investigate the absorption kinetics of cefixime (CFX) after oral administration in humans.
• To compare the goodness-of-fit of four different pharmacokinetic models for CFX absorption.
• To identify the most suitable model for describing CFX oral absorption.

Main Methods:

• Oral administration of 400 mg cefixime (CFX) to 10 healthy Chinese men.
• Application of four absorption models: first-order (M1), zero-order (M0), Michaelis-Menten (MM), and MM with an absorption window (MM-delta t).
• Evaluation of model fit using R-squared (r2) and Akaike Information Criterion (AIC).

Main Results:

• The Michaelis-Menten type absorption with an absorption window (MM-delta t) model demonstrated superior fit to the CFX concentration data.
• Estimated kinetic parameters included Vmax' (10.80 ± 3.80 mg/L/h), Km' (88.31 ± 2.75 µg/mL), absorption window delay (delta t = 4.75 ± 0.85 h), half-life (T1/2 = 4.20 ± 0.92 h), time to maximum concentration (Tmax = 5.20 ± 0.92 h), and maximum concentration (Cmax = 6.04 ± 1.70 mg/L).

Conclusions:

• The MM-delta t model provides a more accurate representation of cefixime (CFX) oral absorption kinetics in humans.
• This finding highlights the importance of considering absorption delays and non-linear absorption mechanisms for CFX.
• The characterized kinetic parameters can inform future dosing strategies and clinical use of cefixime.