Ceftizoxime kinetics and renal handling.

Area of Science:

• Pharmacology
• Nephrology
• Infectious Diseases

Background:

• Ceftizoxime is a third-generation cephalosporin antibiotic.
• Understanding its pharmacokinetic profile and renal handling is crucial for optimizing therapeutic efficacy.
• The influence of co-administered drugs, such as probenecid, on ceftizoxime excretion requires investigation.

Purpose of the Study:

• To determine the pharmacokinetics of ceftizoxime following intravenous (IV) and intramuscular (IM) administration.
• To investigate the effect of probenecid on the renal excretion and serum levels of ceftizoxime.
• To elucidate the mechanism of renal handling of ceftizoxime.

Main Methods:

• Administered 1000 mg of ceftizoxime via IV and IM routes to human subjects.
• Measured peak serum levels and half-life (t 1/2) at various time points.
• Investigated the effect of co-administering probenecid with IM ceftizoxime on serum concentrations and elimination.

Main Results:

• Peak serum level after 1000 mg IV was 60.5 microgram/ml with a t 1/2 of 1.4 hr.
• Peak serum level after 1000 mg IM was 40.9 microgram/ml at 1 hr.
• Probenecid co-administration increased peak serum levels (44.3 microgram/ml) and extended the t 1/2 to 2.29 hr, with significantly higher serum levels at 2, 4, 6, and 8 hr (P < 0.01).

Conclusions:

• Ceftizoxime is actively secreted by the renal tubules.
• Probenecid significantly reduces the renal excretion of ceftizoxime, leading to higher and more prolonged serum concentrations.
• This interaction suggests a potential for dose adjustment or therapeutic synergy when ceftizoxime and probenecid are used concurrently.