Moxalactam--absorption, excretion, distribution, and metabolism

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Clinical Pharmacology

Background:

• Moxalactam is a novel beta-lactam antibiotic.
• Understanding its pharmacokinetic profile is crucial for effective therapeutic use.

Purpose of the Study:

• To characterize the pharmacokinetic properties of moxalactam in healthy volunteers.
• To compare moxalactam pharmacokinetics with cefazolin.
• To investigate the influence of probenecid and renal impairment on moxalactam levels.

Main Methods:

• Single and multiple dose administration of moxalactam via intramuscular injection, intravenous bolus, and infusion.
• Serum, urine, and bile concentrations were measured.
• Creatinine clearance was assessed in subjects with renal impairment.
• Crossover study comparing moxalactam and cefazolin.

Main Results:

• Moxalactam serum levels were dose-proportional after administration.
• Peak serum concentration (1 g IV bolus) was 201.0 µg/ml with a half-life of 126 min.
• 90.5% of the dose was excreted in urine within 10 hours.
• No drug accumulation occurred with multiple dosing.
• Probenecid did not affect serum levels or urinary recovery.
• Markedly prolonged half-life observed in subjects with low creatinine clearance (≤10 ml/min).
• Higher bile concentrations of moxalactam compared to cefazolin.
• Sputum concentrations ranged from 1.84-2.11 µg/ml.

Conclusions:

• Moxalactam exhibits predictable pharmacokinetics in healthy individuals.
• Renal excretion is likely via glomerular filtration.
• Renal impairment significantly impacts moxalactam elimination.
• Moxalactam demonstrates favorable distribution into bile and sputum.