Absorption, Distribution and Excretion
Ceftriaxone is administered by injection only, either intramuscularly or intravenously. The bioavailability of oral ceftriaxone is less than 1%. Ceftriaxone is primarily excreted in the urine (33-67%). The remainder is secreted in bile and ultimately excreted in the feces. The apparent volume of distribution (VOD) of intravenously or intramuscularly administered ceftriaxone in healthy patients is 5.78 to 13.5 liters. In patients with sepsis, the VOD is 6.48 to 35.2 liters. Ceftriaxone has good cerebrospinal fluid penetration and is effective in treating bacterial meningitis. In healthy adults, plasma clearance after administration of 0.15-3 g of ceftriaxone 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, the total drug clearance of ceftriaxone was 0.96 L/h (0.55–1.28 L/h), and the free drug clearance was 1.91 L/h (1.46–6.20 L/h). Metabolism/Metabolites: The metabolism of ceftriaxone is negligible. Ceftriaxone is primarily excreted unchanged in the urine via glomerular filtration (60%) and bile (40%) (A633). Excretion pathway: 33% to 67% of the ceftriaxone dose is excreted unchanged in the urine, with the remainder excreted via bile and ultimately in the feces as a microbiologically inactive compound. Half-life: 5.8–8.7 hours. The half-life of ceftriaxone is 5.8–8.7 hours. It is estimated that the half-life of ceftriaxone in middle ear effusion is 25 hours.

Toxicity Summary
Ceftriaxone works by inhibiting the synthesis of peptidoglycans in bacterial cell walls. The β-lactam moiety of ceftriaxone binds to carboxypeptidase, endopeptidase, and transpeptidase on the bacterial cell membrane. These enzymes are involved in cell wall synthesis and cell division. Ceftriaxone, by binding to these enzymes, leads to the formation of defective cell walls and cell death. Hepatotoxicity
Parenteral administration of ceftriaxone is associated with biliary sludge in 3% to 46% of patients. The incidence may be higher in children than in adults and is associated with higher doses, longer treatment durations, and possible fasting or dehydration. This syndrome is called "pseudo-cholelithiasis" because the biliary sludge and stones are primarily composed of ceftriaxone and resolve spontaneously upon discontinuation of the drug, meaning surgery can be avoided. Most cases are mild or asymptomatic. Up to 5% of patients with pseudo-cholelithiasis have been reported to develop significant cholecystitis symptoms. Normally, even with biliary colic, serum enzyme and bilirubin levels remain normal. However, in rare cases, cholestatic jaundice or cholelithic pancreatitis may occur, which can be severe and require surgical intervention. Symptoms of biliary sludge and gallbladder disease may appear within days of starting treatment but usually subside rapidly after discontinuing ceftriaxone, although biliary sludge and gallstones may still be detectable by ultrasound for months. Ceftriaxone can also cause immune-mediated cholestatic hepatitis, similar to hepatitis caused by other cephalosporins. This reaction is specific and very rare. Symptoms such as abdominal pain, nausea, itching, and jaundice may appear within 1 to 4 weeks of starting treatment and may worsen within 1 to 2 weeks after discontinuing the antibiotic. Serum enzyme elevations are in a cholestatic pattern, accompanied by immune-mediated reactions such as fever, rash, and eosinophilia. Liver damage is usually mild and self-limiting.
Probability Score: B (Ceftriaxone is highly likely to cause clinically significant liver damage and may lead to biliary sludge and "pseudo-stones," which are caused by ceftriaxone crystallizing in the bile of the gallbladder or biliary system).

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Use during pregnancy and lactation
◉ Overview of use during lactation
Limited information suggests that the concentration of ceftriaxone in breast milk is low and is not expected to have adverse effects on breastfed infants. There are reports that cephalosporins occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Ceftriaxone can be used in breastfeeding women.
◉ Effects on breastfed infants
A mother who exclusively breastfed her 52-day-old infant developed a soft tissue infection. She received the following treatment: intravenous teicoplanin 400 mg every 12 hours for 3 times; then 400 mg daily for 5 days; intravenous ceftriaxone 1 g once daily; and topical mupirocin cream twice daily. Careful follow-up showed that her infant experienced no adverse reactions.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
The protein binding rate of ceftriaxone is 95%.

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Toxicity data
LD50: >10000 mg/kg (oral, rat)

[1]. Ceftriaxone: a third-generation cephalosporin. Drug Intell Clin Pharm. 1985 Dec;19(12):900-6.

[2]. Molecular docking, molecular dynamics simulations and in vitro screening reveal cefixime and ceftriaxone as GSK3β covalent inhibitors. RSC Adv. 2023 Apr 11;13(17):11278-11290.

[3]. Ceftriaxone Protects Astrocytes from MPP(+) via Suppression of NF-κB/JNK/c-Jun Signaling. Mol Neurobiol. 2015 Aug;52(1):78-92.

[4]. Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B. Carcinogenesis. 2012 Dec;33(12):2548-57.

[5]. Ceftriaxone improves hepatorenal damages in mice subjected to D-galactose-induced aging. Life Sci. 2020 Oct 1;258:118119.

[6]. Positive effects of ceftriaxone on pentylenetetrazol-induced convulsion model in rats. Int J Neurosci. 2016;126(1):70-5.

[7]. Anti-allodynic and anti-hyperalgesic effects of ceftriaxone in streptozocin-induced diabetic rats. Neurosci Lett. 2011 Mar 10;491(1):23-5.

Pharmacodynamics
Ceftriaxone is a cephalosporin/cephamycin β-lactam antibiotic used to treat bacterial infections caused by susceptible bacteria (usually Gram-positive). Ceftriaxone has in vitro activity against Gram-positive aerobic bacteria, Gram-negative aerobic bacteria, and anaerobic bacteria. Its bactericidal activity stems from its inhibition of cell wall synthesis and it exerts its effect by binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against the hydrolytic activity of a variety of β-lactamases, including penicillinase, cephalosporinase, and extended-spectrum β-lactamases. However, bacterial resistance to ceftriaxone is often due to β-lactamase hydrolysis, altered PBPs, or decreased bacterial cell permeability. Ceftriaxone should not be mixed with calcium-containing diluents/products or infused through the same intravenous line, as these may cause ceftriaxone precipitation. Use of ceftriaxone may also lead to biliary sludge or pseudolithiasis of the gallbladder.

C18H17N8NAO7S3

576.56

598.009

74578-69-1

Ceftriaxone;73384-59-5;Ceftriaxone sodium hydrate;104376-79-6

5479530

White to off-white solid powder

>155 °C
> 155 °C

-1.3

4

13

8

36

1110

2

S1C([H])([H])C(C([H])([H])SC2=NC(C(=NN2C([H])([H])[H])[O-])=O)=C(C(=O)[O-])N2C([C@]([H])([C@@]12[H])N([H])C(/C(/C1=C([H])SC(N([H])[H])=N1)=N\OC([H])([H])[H])=O)=O.[Na+].[Na+]

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

Ceftriaxone Sodium Ceftriaxonesodium Ceftriaxone sodium hydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~50 mg/mL (~83.54 mM)
H2O : ≥ 40 mg/mL (~66.83 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.18 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 (4.18 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: 100 mg/mL (167.07 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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