A Comprehensive Monograph on Ceftriaxone (DB01212)

1.0 Abstract and Key Characteristics

Ceftriaxone is a parenteral, small-molecule, third-generation cephalosporin antibiotic renowned for its broad-spectrum bactericidal activity and distinct pharmacokinetic profile.[1] It is classified as a beta-lactam antibiotic, exerting its effect through the irreversible inhibition of bacterial cell wall synthesis by binding to essential penicillin-binding proteins (PBPs).[2] A defining clinical feature of ceftriaxone is its exceptionally long elimination half-life, which averages between 5.8 and 8.7 hours in healthy adults, a characteristic that facilitates convenient once or twice-daily dosing regimens and enhances its suitability for outpatient parenteral antibiotic therapy (OPAT).[1]

The drug's disposition in the body is characterized by a unique dual elimination pathway; approximately 33-67% of an administered dose is excreted unchanged in the urine via glomerular filtration, with the remainder secreted into the bile and subsequently eliminated through the feces as inactive metabolites.[3] This balanced clearance mechanism provides a degree of safety in patients with isolated renal impairment, as the biliary route can compensate. This property, combined with its excellent penetration into a wide range of tissues, body fluids, and, most notably, the cerebrospinal fluid (CSF), establishes ceftriaxone as a cornerstone therapy for a multitude of severe infections, including bacterial meningitis, sepsis, pneumonia, and complicated urinary tract infections.[1]