Norfloxacin disposition after sequentially increasing oral doses.

Area of Science:

• Pharmacology
• Clinical Pharmacy

Background:

• Norfloxacin is a fluoroquinolone antibiotic used to treat various bacterial infections.
• Understanding its pharmacokinetic profile is crucial for optimizing therapeutic efficacy and safety.

Purpose of the Study:

• To evaluate the pharmacokinetics of single oral doses of norfloxacin in healthy male volunteers.
• To assess the dose-dependent effects of norfloxacin on serum and urine concentrations and identify potential safety concerns.

Main Methods:

• A double-blind, placebo-controlled study involving 14 healthy male volunteers.
• Administration of single oral doses of norfloxacin (200-1,600 mg) or placebo weekly.
• Quantification of norfloxacin in serum and urine using high-performance liquid chromatography with UV detection.

Main Results:

• Norfloxacin serum concentrations peaked 1-2 hours post-dose, with dose-proportional increases in peak levels and AUC.
• Elimination half-life was approximately 7 hours, consistent across all doses.
• Urine concentrations also peaked early, with significant excretion of unchanged norfloxacin (approx. 30%).
• Crystalluria was observed at higher doses (1,200 and 1,600 mg), but not at lower doses.

Conclusions:

• Norfloxacin exhibits dose-proportional pharmacokinetics in healthy males within the studied dose range.
• The drug is primarily excreted unchanged in urine, and high doses may lead to crystalluria.
• These findings are important for guiding norfloxacin dosing strategies and monitoring for potential adverse effects.