CEFTRIAXONE Chemical Properties
CEFTRIAXONE Usage And Synthesis
- Uses Possible carcinogen. Packaged under nitrogen
- DefinitionChEBI: A cephalosporin compound having 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetylamino and [(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl side-groups.
- Antimicrobial activityMost β-lactamase-producing enterobacteria are highly susceptible, as are streptococci (but not enterococci) and fastidious Gram-negative bacilli, although brucellae are less sensitive (MIC 0.25–2 mg/L). Treatment failure has been reported in tularemia. Ps. aeruginosa, mycoplasmas, mycobacteria and L. monocytogenes are resistant.
- Acquired resistanceCeftriaxone is hydrolyzed by some chromosomal enzymes, including those of Enterobacter spp. and B. fragilis. Derepression of chromosomal β-lactamase production can cause resistance in some species of Gram-negative bacilli in vitro and has been observed in patients.
- PharmacokineticsCmax 500 mg/L intramuscular: c. 40 mg/L after 2 h
1 g intravenous (15–30-min infusion): c. 120–150 mg/L end infusion
Plasma half-life: 6–9 h
Volume of distribution: 0.15 L/kg
Plasma protein binding: 95%
Ceftriaxone penetrates well into normal body fluids and natural and experimental exudates. In children treated for meningitis with 50 or 75 mg/kg intravenously over 10–15 min, mean peak CSF concentrations ranged from 3.2 to 10.4 mg/L, with lower values later in the disease. In patients receiving 2 g before surgery, concentrations in cerebral tissue reached 0.3–12 mg/L. In patients with pleural effusions of variable etiology given a 1 g intravenous bolus, concentrations of 7–8.7 mg/L were found at 4–6 h. In patients with exacerbations of rheumatoid arthritis receiving the same dose, joint fluid contained concentrations close to those in the serum, but with wide individual variation. Tissue fluid:serum ratios have varied from around 0.05 in bone and muscle to 0.39 in cantharides blister fluid. The apparent volume of distribution is increased in patients with cirrhosis where the drug rapidly enters the ascitic fluid, but its elimination kinetics are unaffected.
Ceftriaxone rapidly crosses the placenta, maternal doses of 2 g intravenously over 2–5 min producing mean concentrations in cord blood of 19.5 mg/L, a mean cord:maternal serum ratio of 0.18; and in amniotic fluid 3.8 mg/L, a fluid:maternal serum ratio of 0.04. The plasma elimination half-life appears to be somewhat shortened in pregnancy (5–6 h). Some appear in the breast milk, the milk:serum ratio being about 0.03–0.04, secretion persisting over a long period with a half-life of 12–17 h.
Metabolism and excretion
Ceftriaxone is not metabolized. Biliary excretion is unusually high, 10–20% of the drug appearing in the bile in unchanged form, with concentrations up to 130 mg/g in biopsied liver tissue from patients receiving 1 g intravenously over 30 min. The insoluble calcium salt may precipitate in the bile leading to pseudolithiasis. About half the dose appears in the urine over the first 48 h, somewhat more (c. 70%) in neonates. Excretion is almost entirely by glomerular filtration, since there is only a small effect of probenecid on the excretion of the drug. The half-life is not linearly correlated with creatinine clearance in renal failure and, in keeping with the low free plasma fraction, it is not significantly removed by hemodialysis. The volume of distribution is not affected by renal failure.
- Clinical UseUses of Ceftriaxone are similar to those of cefotaxime, the long half-life offering the advantage of once-daily administration. It is used in the treatment of acute bacterial meningitis and as an alternative to rifampicin (rifampin) in the prophylaxis of meningococcal disease.
- Side effectsReactions are those common to other cephalosporins. Mention has been made of thrombocytopenia, thrombocytosis, leukopenia, eosinophilia abdominal pain, phlebitis, rash, fever and increased values in liver function tests. Diarrhea is common and suppression of the aerobic and anaerobic fecal flora has been associated with the appearance of resistant bacteria and yeasts.
Biliary pseudolithiasis due to concretions of insoluble calcium salt has been described in adults but principally in children. The precipitates can be detected in a high proportion of patients by ultrasonography and can occasionally cause pain, but resolve on cessation of treatment. Ceftriaxone is better avoided in patients with pre-existing biliary disease, but the principal hazard appears to be misdiagnosis of gallbladder disease and unnecessary surgery.
CEFTRIAXONE Preparation Products And Raw materials
- Potassium chloride Sodium bicarbonate 3-Hydroxytyramine Phloroglucinol HACHIMYCIN N-ACETYLGLYCINAMIDE Trimethoprim Magnesium sulfate PIERICIDIN A Ferritin Ceftriaxone sodium Cefoperazone sodium +sulbactam sodium(1:1/2:1) Thiotriazinone Cefetamet hydrochloride Ceftizoxime Desfuroyl Ceftiofur CEFTRIAXONE Ceftriaxone sodium
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