The medication ketorolac is a non-steroidal anti-inflammatory. The IC50 values for COX-1 and COX-2, respectively, indicate that the compound is a non-selective COX inhibitor [1].

The LPS endotoxin-induced rise in anterior chamber FITC-dextran and the rise in PGE2 content in the aqueous humor are nearly entirely inhibited by ketorolac tromethamine (0.4%) [1]. Intravenous ketorolac (30 mg/kg) reverses rats' hyperalgesia quickly. Additionally, ketorolac can lower PGE2 levels in rats and lessen paw PG synthesis and carrageenan-induced hyperalgesia [1]. Rat alveolar socket volume fraction of trabecular bone produced is unaffected by ketorolac (4 mg/kg/day) taken orally [2]. Rat ischemia cell death, including cytoplasmic eosinophilia, cellular disarray, and nuclear pyknosis, is lessened by ketorolac (60 μg/10 μL). Additionally, ketorolac can enhance hind limb motor function, substantially decrease neuronal death, and have a long-term survival rate comparable to the control group [3].

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
At normal oral doses, ketorolac concentrations in breast milk are low, but higher doses or nasal spray concentrations have not been measured in breast milk. In some hospital protocols, short-term (usually 24 hours) use of ketorolac injections after cesarean section has not been shown to be harmful to breastfed infants. However, due to the small volume of colostrum, the amount of ketorolac ingested by the infant from colostrum is very low. Some evidence suggests that intravenous ketorolac as part of a multimodal analgesia regimen after cesarean section reduces the rate of exclusive breastfeeding failure compared to patient-controlled intravenous morphine analgesia. Ketorolac has potent antiplatelet activity and may cause gastrointestinal bleeding. The manufacturer notes that ketorolac is contraindicated during lactation; therefore, alternative medications are recommended when milk production is high, especially in the first 24 to 72 hours postpartum, particularly when nursing newborns or premature infants.
The use of ketorolac eye drops by the mother is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after the eye drops are instilled, press the tear duct near the corner of the eye with your finger for at least 1 minute, then blot away any excess medication with absorbent tissue.
◉ Effects on breastfed infants
A randomized, double-blind study compared the efficacy of standard care to that of standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketorolac during fascial suturing) to mothers who underwent cesarean section (n = 60) versus mothers who underwent standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketorolac during fascial suturing) (n = 60). In the first month postpartum, there were no significant differences between the two groups in terms of neonatal growth abnormalities, feeding difficulties, or the incidence of neonatal sedation or respiratory depression.
◉ Impact on Lactation and Breast Milk
A randomized, double-blind study compared postpartum outcomes in mothers who underwent cesarean section (n = 60) receiving standard care versus those who received standard care plus multimodal analgesia (including a single intramuscular injection of 60 mg ketodrolic acid during fascial suturing) (n = 60). In the first month postpartum, breastfeeding rates were not significantly different between the two groups (78% and 79%, respectively).
In a study comparing standard care versus enhanced recovery after cesarean section, the enhanced recovery program included a fixed intravenous dose of 15 mg ketodrolic acid every 6 hours for 24 hours postpartum, while the standard program included on-demand intravenous injections of 15 mg ketodrolic acid. Patients using the enhanced recovery program (n = 58) had a higher rate of exclusive breastfeeding (67%) than those using the standard program (48%; n = 60).
A retrospective study evaluated 1349 women who underwent cesarean section and received ketodrolic acid within 15 minutes of the end of surgery. The results showed no difference in pain control during the first 6 hours post-surgery or the proportion of women breastfeeding at discharge. A prospective cohort study compared two pain control regimens after cesarean section: (1) patient-controlled analgesia (PCA) with morphine and ibuprofen administered at set times for the first 12 hours post-surgery, followed by continued ibuprofen administration at set times, with hydrocodone-acetaminophen added if necessary; (2) a multimodal analgesia regimen including: (3) oral acetaminophen 1000 mg every 8 hours post-surgery; (4) intravenous ketorolac 30 mg, followed by 15 mg every 8 hours for 24 hours; (5) oral ibuprofen 600 mg every 8 hours for the remainder of post-surgery, with opioids used only when necessary. Among women who planned to exclusively breastfeed at admission, the proportion of women using formula before discharge was lower in the multimodal analgesia group than in the conventional analgesia group (9% vs. 12%).

[1]. Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006 Jun;22(6):1133-40.

[2]. Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats. J Appl Oral Sci. 2010 Dec;18(6):630-4.

[3]. Intrathecal ketorolac pretreatment reduced spinal cord ischemic injury in rats. Anesth Analg. 2005 Apr;100(4):1134-9.

ROX-888 is the lead candidate drug for ROXRO and is currently undergoing a Phase III clinical trial for the treatment of acute pain, including postoperative pain. Ketoroxypropyl tromethamine is the tromethamine salt of ketoroxylic acid, a synthetic pyrrolizine carboxylic acid derivative with anti-inflammatory, analgesic, and antipyretic effects. Ketoroxypropyl tromethamine is a non-selective cyclooxygenase (COX) inhibitor that simultaneously inhibits COX-1 and COX-2 enzymes. This drug exerts its anti-inflammatory effect by inhibiting COX-2, which is undetectable in most tissues but highly expressed at sites of inflammation. Since COX-1 is expressed in almost all tissues, the drug's inhibition of COX-1 prevents the normal production of prostaglandins. Prostaglandins play a role in maintaining normal bodily functions, including protecting the gastrointestinal tract, regulating renal blood flow, and participating in platelet aggregation. Therefore, COX-1 inhibitors are often associated with adverse reactions such as gastrointestinal toxicity and nephrotoxicity. Ketoroxypropyl tromethamine is a pyrrolizine carboxylic acid derivative related to the structure of indomethacin. It is a nonsteroidal anti-inflammatory drug (NSAID) used for postoperative analgesia and to inhibit cyclooxygenase activity. See also: Ketodrolic acid (containing the active ingredient)... See more...

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Drug Indications
Studied for the treatment/relief of pain (acute or chronic).

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Mechanism of Action
ROX-888 is an intranasal formulation of the widely used injectable analgesic ketordrolic acid. It effectively relieves moderate to severe pain caused by acute illnesses without the serious side effects of opioid analgesics.

C26H28FN3O9

545.52

376.163

74103-07-4

Ketorolac;74103-06-3;(S)-Ketorolac;66635-92-5;(R)-Ketorolac;66635-93-6

84003

White to off-white solid powder

493.2ºC at 760 mmHg

160-161ºC

252.1ºC

0.652

5

7

6

27

430

0

2-amino-2-(hydroxymethyl)propane-1,3-diol 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylate

BWHLPLXXIDYSNW-UHFFFAOYSA-N

2-amino-2-(hydroxymethyl)propane-1,3-diol;5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid

Acular Godek Sprix Syntex Toradol Ketorolac tromethamine

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)

H2O : ~100 mg/mL (~265.67 mM)
DMSO : ≥ 30 mg/mL (~79.70 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.53 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 20.8 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: ≥ 2.08 mg/mL (5.53 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 20.8 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: ≥ 2.08 mg/mL (5.53 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (265.67 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.)