Sign Out
Pharmacology: Pharmacodynamics: Ceftriaxone inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Pharmacokinetics: Absorption: After intravenous bolus administration of ceftriaxone 500 mg and 1 g, mean peak plasma ceftriaxone levels are approximately 120 and 200 mg/L respectively. After intravenous infusion of ceftriaxone 500 mg, 1 g and 2 g, the plasma ceftriaxone levels are approximately 80, 150 and 250 mg/L respectively. Following intramuscular injection, mean peak plasma ceftriaxone levels are approximately half those observed after intravenous administration of an equivalent dose. The maximum plasma concentration after a single intramuscular dose of 1 g is about 81 mg/L and is reached in 2-3 hours after administration. The area under the plasma concentration-time curve after intramuscular administration is equivalent to that after intravenous administration of an equivalent dose.
Distribution: The volume of distribution of ceftriaxone is 7-12 L. Concentrations well above the minimal inhibitory concentrations of most relevant pathogens are detectable in tissue including lung, heart, biliary tract/liver, tonsil, middle ear and nasal mucosa, bone, and in cerebrospinal, pleural, prostatic and synovial fluids. An 8-15% increase in mean peak plasma concentration (Cmax) is seen on repeated administration; steady state is reached in most cases within 48-72 hours depending on the route of administration.
Penetration into particular tissues: Ceftriaxone penetrates the meninges. Penetration is greatest when the meninges are inflamed. Mean peak ceftriaxone concentrations in CSF in patients with bacterial meningitis are reported to be up to 25% of plasma levels compared to 2% of plasma levels in patients with uninflamed meninges. Peak ceftriaxone concentrations in CSF are reached approximately 4-6 hours after intravenous injection. Ceftriaxone crosses the placental barrier and is excreted in the breast milk at low concentrations.
Protein binding: Ceftriaxone is reversibly bound to albumin. Plasma protein binding is about 95% at plasma concentrations below 100 mg/L. Binding is saturable and the bound portion decreases with rising concentration (up to 85% at a plasma concentration of 300 mg/L).
Biotransformation: Ceftriaxone is not metabolised systemically; but is converted to inactive metabolites by the gut flora.
Elimination: Plasma clearance of total ceftriaxone (bound and unbound) is 10-22 mL/min. Renal clearance is 5-12 mL/min. 50-60% of ceftriaxone is excreted unchanged in the urine, primarily by glomerular filtration, while 40-50% is excreted unchanged in the bile. The elimination half-life of total ceftriaxone in adults is about 8 hours.
