Time-dependent elimination of cinoxacin in rats

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Urochemistry and Renal Physiology

Background:

• Cinoxacin is an acidic antibacterial agent (pKa 4.60).
• Urinary pH fluctuates based on feeding status in rats, impacting drug elimination.

Purpose of the Study:

• To investigate the influence of varying urinary pH on cinoxacin pharmacokinetics.
• To determine the role of urinary pH in the elimination of cinoxacin.

Main Methods:

• Pharmacokinetic analysis of cinoxacin in fasted and nonfasted rats with monitored urinary pH.
• One-compartment open model used to calculate elimination rate constants.
• Comparison of plasma concentration-time curves after oral and intravenous administration.

Main Results:

• Urinary pH significantly correlated with cinoxacin elimination rate constants.
• Fasted rats exhibited a prolonged half-life and a threefold larger area under the plasma concentration-time curve for cinoxacin compared to nonfasted rats.
• Findings suggest urinary pH, not protein binding, is a key factor in cinoxacin elimination variability.

Conclusions:

• Urinary pH is a critical determinant of cinoxacin pharmacokinetics, influencing its elimination rate and half-life.
• Food intake-induced physiological changes in urinary pH contribute to the time-dependent elimination of cinoxacin.
• Understanding urinary pH variations is essential for optimizing cinoxacin therapy.