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Pharmacology: Bactericidal action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes. Cephalosporins inhibit bacterial septum and cell wall synthesis, probably by acylation of membrane bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and elongation of susceptible bacteria and lysis frequently occur. Rapidly dividing bacteria are those most susceptible to the action of cephalosporins.
Pharmacokinetics: Ceftriaxone demonstrates non-linear dose-dependent pharmacokinetics because of its protein-binding; about 85 to 95% is bound to plasma protein depending on the plasma concentration of ceftriaxone.
Mean peak plasma concentrations of about 40 and 80 g per mL have been reported 2 hours after intramuscular injection of 0.5 and 1 g of ceftriaxone respectively. The plasma half-life of ceftriaxone is not dependent on the dose and varies between 6 and 9 hours; it may be prolonged in neonates. The half-life does not change appreciably in patients with moderate renal impairment, but it may be prolonged in severe renal impairment especially when there is also hepatic impairment.
Ceftriaxone is widely distributed in body tissues and fluids. It crosses both inflamed and non-inflamed meninges, generally achieving therapeutic concentrations in the CSF. It crosses the placenta and low concentrations have been detected in breast milk. High concentrations are achieved in bile.
About 40 to 65% of a dose of ceftriaxone is excreted unchanged in the urine, principally by glomerular filtration; the remainder is excreted in the bile and is ultimately found in the feces as unchanged drug and microbiologically inactive compounds.
