Ceftriaxone Elimination Half-Life
The elimination half-life of ceftriaxone in adults with normal renal and hepatic function ranges from 5.8 to 8.7 hours, with an average of approximately 8 hours. 1, 2
Pharmacokinetic Parameters in Normal Adults
- The FDA-approved prescribing information specifies that over a 0.15 to 3 gram dose range in healthy adults, elimination half-life values ranged from 5.8 to 8.7 hours 1
- This relatively long half-life among cephalosporins allows for once-daily or twice-daily dosing, as ceftriaxone maintains serum concentrations above the MIC for most susceptible organisms for 12-24 hours 3
- The drug demonstrates 33-67% renal excretion as unchanged drug, with the remainder eliminated via biliary secretion 1, 2
Age-Related Variations
- Neonates (1-8 days old): Half-life averages 19 hours, requiring less frequent dosing 4
- Children (1-6 years): Half-life decreases to 6.3 hours 4
- Elderly patients (75-92 years): Half-life gradually increases to approximately 14 hours 4
- Pediatric patients with bacterial meningitis demonstrate a half-life of 4.3-4.6 hours after 50-75 mg/kg IV doses 1
Impact of Organ Dysfunction
Renal impairment alone causes modest prolongation:
- Mild to moderate renal impairment: Half-life increases to 11.4-12.4 hours 5
- Severe renal impairment or hemodialysis: Half-life extends to 14.7-17.3 hours 5
- Critical point: Dose adjustments are generally not necessary for ceftriaxone dosages up to 2 grams per day in renal impairment alone, due to compensatory biliary elimination 1, 5
Combined renal and hepatic dysfunction causes substantial prolongation:
- Patients with both severe renal failure and hepatic dysfunction demonstrate half-lives ranging from 23.7 to 59.4 hours 6
- This represents a 3-7 fold increase compared to normal subjects and requires dose reduction 6
Hepatic impairment alone:
- Patients with liver disease (without ascites) show minimal change, with half-life of 8.8 hours 1
- Patients with cirrhosis and ascites demonstrate half-life of 9.7 hours, which is not clinically significant 7
Clinical Implications
- The long half-life permits once-daily administration for most infections, improving outpatient parenteral antimicrobial therapy (OPAT) feasibility 3
- Ceftriaxone is not significantly removed by hemodialysis, though a small percentage of dialysis patients show markedly reduced elimination requiring monitoring 1, 2
- Plasma protein binding is 85-95% at therapeutic concentrations, which is reversibly concentration-dependent 1