Absorption, Distribution and Excretion
Ceftriaxone is only given as an injection, either intramuscularly or intravenously. Ceftriaxone is less than 1% bioavailable if given orally.
Ceftriaxone is primarily eliminated in the urine (33-67%). The remainder is eliminated through secretion in the bile and removed from the body via the feces.
The apparent volume of distribution of an intravenous or intramuscular dose in healthy patients is 5.78 to 13.5 L. The volume of distribution of an intravenous or intramuscular dose in septic patients is 6.48 to 35.2 L. Ceftriaxone has good enough CSF penetration to be used as an effective treatment of bacterial meningitis.
The plasma clearance of ceftriaxone in healthy adults receiving a 0.15-3g dose is 0.58 to 1.45 L/hour. The renal clearance of ceftriaxone is 0.32 to 0.73 L/hour. In intensive care unit patients, ceftriaxone's total drug clearance was 0.96L/h (0.55-1.28 L/h), and unbound drug clearance was 1.91 L/h (1.46-6.20 L/h).

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Metabolism / Metabolites
Metabolism of ceftriaxone is negligible.
Ceftriaxone is eliminated unchanged in the urine by glomerular filtration (60%) and bile (40%) (A633).
Route of Elimination: Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds.
Half Life: 5.8-8.7 hours

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Biological Half-Life
The elimination half-life of ceftriaxone is 5.8-8.7 hours. The half-life of ceftriaxone in the middle ear fluid has been estimated to be 25 hours.

Toxicity Summary
Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.

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Hepatotoxicity
Parenteral administration of ceftriaxone has been associated with development of biliary sludge in 3% to 46% of patients. The incidence may be higher in children than adults and is associated with higher doses and longer courses of treatment and possibly with fasting or dehydration. The syndrome is referred to as “pseudolithiasis” as the sludge and stones consist largely of ceftriaxone and they resolve spontaneously when the drug is stopped, indicating that surgery can be avoided. Most cases occur with minimal or no symptoms. Frank symptoms of cholecystitis are reported in up to 5% of patients who develop pseudo-lithiasis. Typically, serum enzymes and bilirubin levels remain normal even with biliary colic, but in rare instances there is cholestatic jaundice or gallstone pancreatitis that can be severe and require surgical intervention. Sludge and symptoms of gallbladder disease can arise within a few days of starting therapy, but typically resolve rapidly once ceftriaxone is stopped, although sludge and gallstones may be detectable by ultrasound for several months.
Ceftriaxone can also lead to an immunoallergic form of cholestatic hepatitis similar to what has been described with other cephalosporins. This reaction is idiosyncratic and is very rare. Symptoms of abdominal pain, nausea, pruritis and jaundice arise within 1 to 4 weeks of initiation of therapy and may worsen for 1 to 2 weeks after stopping the antibiotic. A cholestatic pattern of serum enzyme elevations and immunoallergic features of fever, rash and eosinophilia are common. The injury is usually mild and self-limited.
Likelihood score: B (ceftriaxone is a very likely cause of clinically apparent liver injury and can also lead to biliary sludge and “pseudolithiasis” caused by crystallization of ceftriaxone in bile present in the gallbladder or biliary tree).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that ceftriaxone produce low levels in milk, which are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Ceftriaxone is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
A mother who was exclusively nursing her 52-day-old infant developed a soft-tissue infection. She was treated with intravenous teicoplanin 400 mg every 12 hours for 3 doses, then 400 mg daily for 5 days total, intravenous ceftriaxone 1 gram daily, topical mupirocin cream twice daily. A careful follow-up indicated that her infant had no adverse effects.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Ceftriaxone is 95% protein bound.

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Toxicity Data
LD50: >10 000 mg/kg (Oral, Rat)

:J Biol Chem, 2008. 283(19): p. 13116-23.

Pharmacodynamics
Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.

C18H18N8O7S3

554.579918384552

554.046

73384-59-5

Ceftriaxone sodium hydrate;104376-79-6;Ceftriaxone sodium salt;74578-69-1;Ceftriaxone-d3 disodium;1132650-38-4

5479530

Off-white to yellow solid powder

2.0±0.1 g/cm3

155 °C

1.889

-0.77

4

13

8

36

1110

2

CN1C(=NC(=O)C(=O)N1)SCC2=C(N3[C@@H]([C@@H](C3=O)NC(=O)/C(=N\OC)/C4=CSC(=N4)N)SC2)C(=O)O

VAAUVRVFOQPIGI-SPQHTLEESA-N

InChI=1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1

(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~31.25 mg/mL (~56.35 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)