Ceftriaxone can be administered once daily for serious infections despite its MIC-based pharmacodynamics (time-dependent killing). This is because:
- A Ceftriaxone has concentration-dependent killing, so once-daily high doses are pharmacodynamically superior
- B Ceftriaxone has a post-antibiotic effect (PAE) against gram-negatives of more than 12 hours, reducing the required time above MIC
- C Ceftriaxone has a half-life of 6–9 hours and 85–95% plasma protein binding that maintains free drug levels above the MIC for a sufficient time interval between doses, satisfying the T>MIC target (40–70% of dosing interval) ✓
- D Ceftriaxone is a cephamycin with enhanced stability to beta-lactamases, requiring fewer doses to achieve clinical cure
Correct answer: C. Ceftriaxone has a half-life of 6–9 hours and 85–95% plasma protein binding that maintains free drug levels above the MIC for a sufficient time interval between doses, satisfying the T>MIC target (40–70% of dosing interval)
Explanation
Beta-lactams kill time-dependently (efficacy = T>MIC). Despite this, ceftriaxone's long half-life (~8 h) combined with extensive protein binding (85–95%) creates a large drug reservoir that slowly releases free drug, maintaining free ceftriaxone levels above the MIC for the majority of the 24-hour dosing interval. This satisfies the PD target (T>MIC ≥ 40–70%) with a once-daily regimen. Ceftazidime (shorter t½) requires 8-hourly dosing for the same reason.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.