Ceftriaxone Half-Life
The elimination half-life of ceftriaxone in healthy adults ranges from 5.8 to 8.7 hours, with a mean of approximately 6.5 hours. 1
Half-Life by Patient Population
Healthy Adults
- The FDA label specifies that over a 0.15 to 3 gram dose range in healthy adult subjects, elimination half-life values ranged from 5.8 to 8.7 hours 1
- This extended half-life is what enables once-daily dosing for most infections 2, 3
Pediatric Patients
- In pediatric patients with bacterial meningitis, the elimination half-life is shorter at 4.3 to 4.6 hours 1
- This shorter half-life in children is due to a threefold greater volume of distribution and plasma clearance compared to adults 4
Elderly Patients
- In elderly subjects (mean age 70.5 years), the half-life is slightly prolonged to 8.9 hours 1
- Despite this modest increase, no dosage adjustment is necessary for elderly patients receiving up to 2 grams per day 1
Renal Impairment
The half-life is significantly prolonged in patients with renal dysfunction: 1
- Mild impairment (CrCl 31-60 mL/min): 12.4 hours
- Moderate impairment (CrCl 16-30 mL/min): 11.4 hours
- Severe impairment (CrCl 5-15 mL/min): 15.7 hours
- Hemodialysis patients (CrCl 0-5 mL/min): 14.7 hours
Critically ill patients with renal failure demonstrate even more prolonged elimination (21.4 ± 9.8 hours) compared to non-critically ill patients with similar renal function 5
Ceftriaxone does not require dose adjustment in renal impairment for dosages up to 2 grams per day, as it has dual elimination (renal and biliary) 6, 1
Hepatic Dysfunction
- In patients with liver disease, the half-life is 8.8 hours, which is only minimally different from healthy subjects 1
- No dosage adjustment is necessary for hepatic dysfunction alone 1
Special Pharmacokinetic Considerations
Middle Ear Fluid
- In middle ear fluid of pediatric patients with otitis media, ceftriaxone demonstrates a remarkably prolonged half-life of 25 hours 1
- This extended tissue half-life supports the effectiveness of single-dose therapy for certain infections 1
Critically Ill Patients
- In critically ill patients with normal renal function, there is increased ceftriaxone clearance (100% higher than normal subjects) and increased volume of distribution (90% higher), but the elimination half-life remains similar at 6.4 ± 1.1 hours 5
- This altered pharmacokinetic profile can result in suboptimal plasma concentrations with standard once-daily dosing in some critically ill patients 5
Clinical Implications
Dosing Frequency
- The long half-life allows for once-daily dosing for most infections, which reduces healthcare costs and improves convenience 2, 3, 7
- For bacterial meningitis, twice-daily dosing (every 12 hours) is required despite the long half-life to ensure adequate CSF concentrations throughout the dosing interval 2
Common Pitfall
- Do not assume once-daily dosing is appropriate for all critically ill patients—those with augmented renal clearance may require twice-daily dosing or higher doses to maintain therapeutic concentrations 5