Nalidixic acid kinetics after single and repeated oral doses

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Analytical Chemistry

Background:

• Nalidixic acid (NA) is an antibiotic requiring kinetic and metabolic understanding.
• Previous studies may lack detailed analysis of NA and its metabolites.

Purpose of the Study:

• To investigate the pharmacokinetics of nalidixic acid (NA) and its metabolites, 7-hydroxynalidixic acid (HNA) and 7-carboxynalidixic acid (CNA).
• To determine drug accumulation and therapeutic concentrations after single and multiple dosing regimens.

Main Methods:

• A novel high-pressure liquid chromatographic (HPLC) technique was employed.
• Plasma and urine samples were analyzed for unconjugated NA, HNA, and CNA concentrations.
• Kinetics were assessed after single and 7-day multiple oral doses.

Main Results:

• NA was rapidly absorbed and metabolized to HNA, with both rapidly excreted (t1/2: 6-7 hr).
• CNA was found in urine (~25%) but not plasma; no significant sex differences were observed.
• No significant accumulation of NA or HNA occurred during 7-day treatment.

Conclusions:

• NA and HNA achieve concentrations exceeding the minimum inhibitory concentration for at least 8 hours post-dose.
• The rapid excretion and lack of accumulation suggest a favorable pharmacokinetic profile for NA therapy.