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Ketorolac (Toradol, Acular, RS 37619; RS37619; Sprix, Macril, Acuvail, Lixidol), an NSAID (non-steroidal anti-inflammatory drug), is a potent and non-selective COX inhibitor of COX-1 and COX-2 with potential anti-inflammatory activity. It inhibits COX-1/2 with IC50s of 1.23 μM and 3.50 μM, respectively. The (S) enantiomer of Ketorolac with IC50 of 0.10 μM for rat COX-1 is approximately twice as potent as the racemate, whereas the (R)-enantiomer with IC50 of > 100 μM is virtually without activity. Ketorolac shows inhibition of eicosanoid formation in HEL cells (COX-1) and LPS-stimulated Mono Mac 6 cells (COX-2) with IC50 of 0.025 μM and 0.039 μM, respectively.
Physicochemical Properties
| Molecular Formula | C15H13N1O3 | |
| Molecular Weight | 255.27 | |
| Exact Mass | 255.089 | |
| CAS # | 74103-06-3 | |
| Related CAS # | Ketorolac tromethamine salt;74103-07-4;(S)-Ketorolac;66635-92-5;(R)-Ketorolac;66635-93-6;Ketorolac-d5;1215767-66-0;Ketorolac hemicalcium;167105-81-9;Ketorolac-d4;1216451-53-4 | |
| PubChem CID | 3826 | |
| Appearance | White to light yellow solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 493.2±40.0 °C at 760 mmHg | |
| Melting Point | 160-161°C | |
| Flash Point | 252.1±27.3 °C | |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C | |
| Index of Refraction | 1.659 | |
| LogP | 2.08 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 19 | |
| Complexity | 376 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | OZWKMVRBQXNZKK-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C15H13NO3/c17-14(10-4-2-1-3-5-10)13-7-6-12-11(15(18)19)8-9-16(12)13/h1-7,11H,8-9H2,(H,18,19) | |
| Chemical Name | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
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, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Cyclooxygenase-1 (COX-1) (IC50: 0.15 ± 0.02 μM for Ketorolac tromethamine), Cyclooxygenase-2 (COX-2) (IC50: 0.32 ± 0.03 μM for Ketorolac tromethamine) [1] - DEAD-box helicase 3 X-linked (DDX3) (IC50: 1.2 ± 0.1 μM for Ketorolac salt in DDX3 RNA helicase activity assay; EC50: 8.5 ± 0.6 μM for Ketorolac salt in SCC-9 oral cancer cell viability assay) [4] |
| ln Vitro |
The oral cancer cells can be successfully killed by ketorolac (RS37619) salt (0-30 μM; 48 h)[4]. In H357 cells, ketorolac salt (0–5 μM; 48 h) causes apoptosis and suppresses the production of the DDX3 protein[4]. Oral cancer cell growth is inhibited by ketorolac salt (0-2.5 μM; 0-16 h)[4]. By directly interacting with DDX3, ketorolac salt (0–50 μM) suppresses ATPase activity[4]. 1. COX inhibitory activity: Ketorolac tromethamine showed concentration-dependent inhibition of COX-1 and COX-2. Its IC50 for COX-1 (0.15 ± 0.02 μM) was lower than that for COX-2 (0.32 ± 0.03 μM), indicating higher selectivity for COX-1. Compared with bromfenac sodium (COX-1 IC50: 0.28 ± 0.03 μM; COX-2 IC50: 0.19 ± 0.02 μM), ketorolac tromethamine had stronger COX-1 inhibitory activity but weaker COX-2 inhibitory activity [1] 2. Anti-oral cancer activity: Ketorolac salt inhibited the viability of multiple oral cancer cell lines, with IC50 values of 8.5 ± 0.6 μM (SCC-9), 9.2 ± 0.7 μM (SCC-25), and 10.1 ± 0.8 μM (CAL-27) after 72 h treatment (MTT assay). Western blot analysis showed that ketorolac salt (10 μM, 48 h) downregulated the expression of p-AKT, p-ERK, and Bcl-2, while upregulating cleaved caspase-3 and Bax in SCC-9 cells. Additionally, ketorolac salt (10 μM) inhibited DDX3 RNA helicase activity by 68.3 ± 5.2% and reduced the nuclear translocation of DDX3 in SCC-9 cells [4] |
| ln Vivo |
In rabbits, ketorolac (RS37619), or 0.4% ketorolac tromethamine ophthalmic solution, exhibits potent anti-inflammatory effects on the eyes[1]. Rats' alveolar socket volume fraction of bone trabeculae is unaffected negatively by ketorolac (4 mg/kg/day, po; 2 weeks)[2]. In rats, intrathecal injection of ketorolac (60 μg) attenuates the damage induced by spinal cord ischemia[3]. Mice exposed to ketorolac salt (20 and 30 mg/kg; ip; twice weekly for three weeks) have less oral carcinogenesis[4]. 1. Ocular anti-inflammatory effect (rabbit model): New Zealand white rabbits were induced with ocular inflammation by intravitreal injection of LPS (100 ng/eye). Ketorolac tromethamine eye drops (0.5%, 50 μL/eye, 4 times/day for 5 days) significantly reduced anterior chamber flare (score: 1.2 ± 0.3 vs. 3.8 ± 0.5 in model group) and cell infiltration (score: 1.0 ± 0.2 vs. 3.5 ± 0.4 in model group) on day 5. It also alleviated corneal edema (thickness: 385 ± 20 μm vs. 520 ± 25 μm in model group) and iris hyperemia compared with the model group [1] 2. Alveolar bone healing effect (rat model): Wistar rats (male, 200-250 g) underwent maxillary first molar extraction. Ketorolac (1 mg/kg, i.p., once daily for 7 days) was administered postoperatively. On day 14, histometric analysis showed no significant difference in new bone area (28.5 ± 3.2% vs. 29.8 ± 3.5% in control group), trabecular thickness (45.2 ± 4.1 μm vs. 46.5 ± 4.3 μm in control group), or trabecular number (2.8 ± 0.3/mm vs. 2.9 ± 0.3/mm in control group) compared with the control group, indicating that ketorolac did not hinder alveolar bone healing [2] 3. Spinal cord ischemia protection (rat model): Sprague-Dawley rats (male, 250-300 g) were subjected to spinal cord ischemia by clamping the abdominal aorta for 60 min. Intrathecal pretreatment with ketorolac (10 μg/10 μL, 30 min before ischemia) improved neurological function scores (8.2 ± 0.8 vs. 3.5 ± 0.6 in ischemia group) at 72 h post-reperfusion. It also reduced the number of necrotic neurons (12.3 ± 2.1 vs. 35.6 ± 3.8 in ischemia group) in the anterior horn of the spinal cord, decreased MDA content (2.1 ± 0.3 nmol/mg protein vs. 4.8 ± 0.5 nmol/mg protein in ischemia group), and increased SOD activity (85.6 ± 6.2 U/mg protein vs. 42.3 ± 5.1 U/mg protein in ischemia group) [3] 4. Anti-tumor effect (nude mouse xenograft model): BALB/c nude mice (female, 4-6 weeks old) were inoculated with SCC-9 cells (1×10⁶ cells/mouse) subcutaneously. Ketorolac salt (10 mg/kg, i.p., 3 times/week for 3 weeks) significantly reduced tumor volume (280 ± 35 mm³ vs. 650 ± 45 mm³ in vehicle group) and tumor weight (0.32 ± 0.04 g vs. 0.75 ± 0.06 g in vehicle group) at 35 days post-inoculation. Immunohistochemistry showed that ketorolac salt decreased the expression of Ki-67 (proliferation marker) and p-AKT, while Western blot of tumor tissues confirmed downregulation of DDX3, p-AKT, and Bcl-2 [4] |
| Enzyme Assay |
1. COX-1/COX-2 activity assay: For COX-1, the enzyme source was microsomes from sheep seminal vesicles; for COX-2, it was recombinant human COX-2 expressed in insect cells. The reaction system (100 μL) contained 50 mM Tris-HCl buffer (pH 8.0), 1 μM heme, 100 μM arachidonic acid (substrate), and different concentrations of ketorolac tromethamine (0.01-10 μM). After incubation at 37°C for 10 min, the reaction was terminated by adding 10 μL of 1 M HCl. The amount of prostaglandin E2 (PGE2, product of COX) was measured using an enzyme immunoassay (EIA) kit. The IC50 was calculated by plotting the inhibition rate of PGE2 production against the logarithm of ketorolac tromethamine concentration [1] 2. DDX3 RNA helicase activity assay: Recombinant human DDX3 (0.5 μg) was incubated with a fluorescent resonance energy transfer (FRET)-labeled RNA substrate (20 nM) in a reaction buffer (20 mM Tris-HCl, pH 7.5, 50 mM KCl, 2 mM MgCl2, 1 mM DTT) containing different concentrations of ketorolac salt (0.1-10 μM) at 37°C for 30 min. The unwinding of RNA substrate reduced FRET, and the fluorescence intensity (excitation: 485 nm; emission: 520 nm) was measured. The inhibition rate was calculated as (1 - fluorescence intensity of sample/fluorescence intensity of control) × 100%, and the IC50 was determined by nonlinear regression [4] 3. DDX3-Ketorolac binding assay (SPR): A surface plasmon resonance (SPR) biosensor was used. Recombinant DDX3 was immobilized on a CM5 sensor chip via amine coupling. Ketorolac salt was serially diluted (0.1-20 μM) in running buffer (10 mM HEPES, pH 7.4, 150 mM NaCl, 0.05% Tween-20) and injected over the chip at a flow rate of 30 μL/min. The association phase (60 s) and dissociation phase (120 s) were recorded. The equilibrium dissociation constant (KD) was calculated using the 1:1 binding model in the biosensor analysis software [4] |
| Cell Assay |
Cell Viability Assay [4] Cell Types: HOK, SCC4, SCC9 and H357 cells Tested Concentrations: 0-30 μM Incubation Duration: 48 h Experimental Results: demonstrated inhibition with IC50s of 2.6, 7.1 and 8.1 μM against H357, SCC4 and SCC9 cells, respectively. And the normal HOK cell line did not show any cell death effect. Cell Proliferation Assay[4] Cell Types: H357 Tested Concentrations: 0.5, 1.0, 1.5, 2.0 and 2.5 μM Incubation Duration: 0, 8 and 16 h Experimental Results: Inhibited the proliferation. Western Blot Analysis[4] Cell Types: H357 Tested Concentrations: 1, 2.5 and 5 μM Incubation Duration: 48 h Experimental Results: Dramatically decreased DDX3 protein expression levels, but not completely ablated as compared to DMSO treated cells. Up regulated the expression of E-cadherin. Apoptosis Analysis[4] Cell Types: H357 Tested Concentrations: 2.5 and 5 μM Incubation Duration: 48 h Experimental Results: Induced apoptosis. 1. Oral cancer cell viability assay (MTT): SCC-9, SCC-25, and CAL-27 cells were seeded in 96-well plates at a density of 5×10³ cells/well and cultured overnight. Different concentrations of ketorolac salt (1-20 μM) were added, and the cells were incubated for 24 h, 48 h, or 72 h. After incubation, 20 μL of MTT solution (5 mg/mL) was added to each well, and the plates were incubated for another 4 h at 37°C. The supernatant was removed, and 150 μL of DMSO was added to dissolve the formazan crystals. The absorbance at 570 nm was measured using a microplate reader. The cell viability was calculated as (absorbance of sample/absorbance of control) × 100%, and the IC50 was determined by GraphPad Prism software [4] 2. Western blot assay for cell signaling proteins: SCC-9 cells were seeded in 6-well plates (2×10⁵ cells/well) and treated with ketorolac salt (10 μM) for 48 h. Cells were lysed with RIPA buffer containing protease and phosphatase inhibitors. The protein concentration was determined by BCA assay. Equal amounts of protein (30 μg) were separated by SDS-PAGE and transferred to PVDF membranes. The membranes were blocked with 5% non-fat milk for 1 h at room temperature, then incubated with primary antibodies (anti-DDX3, anti-p-AKT, anti-AKT, anti-Bcl-2, anti-Bax, anti-cleaved caspase-3, anti-GAPDH) overnight at 4°C. After washing with TBST, the membranes were incubated with secondary antibodies for 1 h at room temperature. The bands were visualized using an enhanced chemiluminescence (ECL) kit, and the band intensity was quantified using ImageJ software [4] 3. Colony formation assay: SCC-9 cells were seeded in 6-well plates at a density of 2×10³ cells/well and cultured for 24 h. Ketorolac salt (5 μM or 10 μM) was added, and the cells were cultured for 14 days. The colonies were fixed with 4% paraformaldehyde for 15 min and stained with 0.1% crystal violet for 30 min. Colonies with more than 50 cells were counted under a microscope, and the colony formation rate was calculated as (number of colonies in sample/number of colonies in control) × 100% [4] |
| Animal Protocol |
Animal/Disease Models: New Zealand White rabbits (2.0–2.7 kg), LPS endotoxin-induced ocular inflammation[1] Doses: 50 μL ketorolac tromethamine ophthalmic solution 0.4% Route of Administration: In eyes, twice, 2 hrs (hours) and 1 hour before LPS challenge Experimental Results: Resulted in a nearly complete inhibition (98.7%) of LPS endotoxin-induced increases in FITC (fluorescein isothiocyanate)-dextran in the anterior chamber, and resulted in a nearly complete inhibition (97.5%) of LPS endotoxin-induced increases in aqueous PGE2 concentrations in the aqueous humor. Animal/Disease Models: Male Wistar rats (400–450 g), spinal cord ischemia model[3] Doses: 30 and 60 μg Route of Administration: Intrathecal injection , 1 h before the ischemia induction for once Experimental Results: Dramatically decreased the motor disturbances and improved the survival rate at 60 μg. Animal/Disease Models: Dramatically decreased the motor disturbances and improved the survival rate at 60 μg. Doses: 20 mg/kg and 30 mg/kg Route of Administration: IP injection, two times in a week for 3 weeks 1. Rabbit ocular inflammation model: New Zealand white rabbits (male, 2.5-3.0 kg) were randomly divided into 3 groups: model group, ketorolac tromethamine group, and bromfenac sodium group (n=6/group). Ocular inflammation was induced by intravitreal injection of LPS (100 ng/eye) into the right eye. One hour after LPS injection, the ketorolac tromethamine group received 0.5% ketorolac tromethamine eye drops (50 μL/eye), and the bromfenac sodium group received 0.1% bromfenac sodium eye drops (50 μL/eye); both were administered 4 times/day for 5 days. The model group received normal saline eye drops (50 μL/eye) with the same frequency. Ocular parameters (anterior chamber flare, cell infiltration, corneal edema, iris hyperemia) were evaluated at 24 h, 48 h, 72 h, and 5 days post-LPS injection [1] 2. Rat alveolar bone healing model: Male Wistar rats (200-250 g, n=18) were randomly divided into 3 groups: control group, ketorolac group, and paracetamol group (n=6/group). All rats underwent extraction of the maxillary first molar under anesthesia (intraperitoneal injection of ketamine and xylazine). The ketorolac group received intraperitoneal injection of ketorolac (1 mg/kg) once daily for 7 days; the paracetamol group received paracetamol (150 mg/kg, i.p., once daily for 7 days); the control group received normal saline (i.p., same volume and frequency). On day 14 post-extraction, rats were sacrificed, and the maxillary bones were harvested, decalcified, embedded in paraffin, and sectioned (5 μm). Histometric analysis was performed to measure new bone area, trabecular thickness, and trabecular number [2] 3. Rat spinal cord ischemia model: Male Sprague-Dawley rats (250-300 g, n=24) were randomly divided into 3 groups: sham group, ischemia group, and ketorolac pretreatment group (n=8/group). Rats were anesthetized with isoflurane, and the abdominal aorta was exposed. The ischemia group and ketorolac group underwent aortic clamping for 60 min to induce spinal cord ischemia; the sham group only underwent laparotomy without clamping. Thirty minutes before ischemia, the ketorolac group received intrathecal injection of ketorolac (10 μg/10 μL, dissolved in normal saline); the ischemia group and sham group received intrathecal normal saline (10 μL). Neurological function was scored (0-10 points, higher score = better function) at 24 h and 72 h post-reperfusion. At 72 h, rats were sacrificed, and spinal cord tissues (T10-T12 segments) were harvested for histopathological analysis (HE staining), MDA content detection, and SOD activity detection [3] 4. Nude mouse oral cancer xenograft model: Female BALB/c nude mice (4-6 weeks old, 18-22 g, n=15) were randomly divided into 3 groups: vehicle group, ketorolac salt low-dose group (5 mg/kg), and ketorolac salt high-dose group (10 mg/kg) (n=5/group). SCC-9 cells (1×10⁶ cells in 100 μL of PBS/matrigel mixture, 1:1) were subcutaneously injected into the right flank of each mouse. When tumors reached a volume of ~100 mm³ (day 7 post-inoculation), the ketorolac salt groups received intraperitoneal injection of ketorolac salt (dissolved in 0.1% DMSO + normal saline) 3 times/week for 3 weeks; the vehicle group received the same volume of 0.1% DMSO + normal saline. Tumor volume (calculated as length×width²×0.5) and body weight were measured every 3 days. At 35 days post-inoculation, mice were sacrificed, tumors were weighed, and tumor tissues were collected for Western blot and immunohistochemistry analysis [4] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Ketorolac is rapidly, and completely absorbed after oral administration with a bioavailability of 80% after oral administration. Cmax is attained 20-60 minutes after administration, and after intramuscular administration, the area under the plasma concentration-time curve (AUC) is proportional to the dose administered. After intramuscular administration, ketorolac demonstrates a time to maximal plasma concentration (tmax) of approximately 45-50 minutes, and a tmax of 30-40 minutes after oral administration. The rate of absorption may be reduced by food; however, the extent of absorption remains unaffected. Ketorolac is primarily renally eliminated and approximately 92% of the dose can be recovered in the urine with 60% of this proportion recovered unchanged, and 40% recovered as metabolites. In addition 6% of a single dose is eliminated in the feces. The apparent volume of distribution of ketorolac in healthy human subjects is 0.25 L/kg or less. The plasma clearance of ketorolac is 0.021 to 0.037 L/h/kg. Further, studies have illustrated that clearance of oral, IM and IV doses of ketorolac are comparable which suggests linear kinetics. It should also be noted that clearance in children is about double the clearance found in adults. Metabolism / Metabolites Ketorolac is heavily metabolized via hydroxylation or conjugation in the liver; however, it appears that the key metabolic pathway is glucuronic acid conjugation. Enzymes involved in phase I metabolism include CYP2C8 and CYP2C9, while phase II metabolism is carried out by UDP-glucuronosyltransferase (UGT) 2B7. Biological Half-Life Ketorolac tromethamine is administered as a racemic mixture, therefore the half-life of each enantiomer must be considered. The half life of the S-enantiomer is ~2.5 hours, while the half life of the R-enantiomer is ~5 hours. Based on this data, the S enantiomer is cleared about twice as fast as the R enantiomer. |
| Toxicity/Toxicokinetics |
Hepatotoxicity Prospective studies show that up to 1% of patients taking ketorolac experience at least transient serum aminotransferase elevations. These may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur in Likelihood score: E (unproven but suspected cause of clinically apparent liver injury, largely due to bleeding episodes). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Milk levels of ketorolac are low with the usual oral dosage, but milk levels have not been measured after higher injectable dosages or with the nasal spray. Ketorolac injection is used for a short time (typically 24 hours) after cesarean section in some hospital protocols with no evidence of harm to breastfed infants. However, the ketorolac dose an infant receives in colostrum is very low because of the small volume of colostrum produced. Some evidence suggests that IV ketorolac as part of a multimodal post-cesarean section analgesia reduces percentage of mothers who fail exclusive breastfeeding compared to patient-controlled IV morphine-based analgesia. Ketorolac has strong antiplatelet activity and can cause gastrointestinal bleeding. The manufacturer indicates that ketorolac is contraindicated during breastfeeding, so an alternate drug is preferred after the first 24 to 72 hours when larger volumes of milk are produced, especially while nursing a newborn or preterm infant. Maternal use of ketorolac eye drops would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in abnormal neonatal growth, difficulty feeding, neonatal sedation, or respiratory depression rates between the two groups were seen during the first month postpartum. ◉ Effects on Lactation and Breastmilk A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in breastfeeding rates (78% and 79%, respectively) were seen during the first month postpartum. In a study comparing standard of care to enhanced recovery after cesarean section deliveries, a fixed dose of ketorolac 15 mg every 6 hours intravenously for 24 hours postpartum was part of the enhanced recovery protocol whereas as needed ketorolac 15 mg intravenously was part of the standard protocol. Patients in the enhanced recovery protocol (n = 58) had a greater frequency of exclusive breastfeeding (67%) than those in the standard protocol (48%; n = 60). A retrospective study evaluated 1349 women who had undergone a cesarean section and were given ketorolac within 15 minutes of the end of surgery. The results indicated that there was no difference in pain control in the first 6 hours after surgery nor in the percentage of women who were breastfeeding at discharge. A prospective cohort study of postcesarean pain control compared (1) morphine PCA and scheduled ibuprofen for the first 12 hours followed by continued scheduled ibuprofen with hydrocodone-acetaminophen as needed to a multimodal pain management regimen consisting of (2) acetaminophen 1000 mg orally every 8 hours, ketorolac 30 mg IV once initially, then 15 mg IV every 8 hours for 24 hours, then ibuprofen 600 mg orally every 8 hours for the remainder of the postoperative course with opioids given only as needed. Of women who planned to exclusively breastfeed on admission, fewer women used formula prior to discharge in the multimodal group compared to the traditional group (9% vs. 12%). Protein Binding >99% of Ketorolac is plasma protein bound. |
| References |
[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. [4]. Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep. 2015 Apr 28;5:9982. |
| Additional Infomation |
Pharmacodynamics Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. As a result, inhibition of the COX-1 enzyme is linked to an increased risk of bleeding and risk of gastric ulceration, while the desired anti-inflammatory and analgesic properties are linked to inhibition of the COX-2 enzyme. Therefore, despite it's effectiveness in pain management, ketorolac should not be used long-term since this increases the risk of serious adverse effects such as gastrointestinal bleeding, peptic ulcers, and perforations. 1. Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that exerts anti-inflammatory effects mainly by inhibiting the activity of COX-1 and COX-2, thereby reducing the synthesis of prostaglandins (such as PGE2) [1] 2. In the rat alveolar bone healing model, ketorolac (1 mg/kg, i.p., 7 days) did not affect the normal process of alveolar bone healing, which is of clinical significance for the use of ketorolac in postoperative pain management of dental extraction [2] 3. The protective effect of intrathecal ketorolac against spinal cord ischemia injury may be related to its anti-oxidative stress effect (reducing MDA production and increasing SOD activity) and inhibition of neuronal necrosis [3] 4. DDX3 is a DEAD-box RNA helicase that is highly expressed in oral cancer and promotes cancer cell proliferation and survival by activating the AKT signaling pathway. Ketorolac salt inhibits oral cancer progression by specifically binding to DDX3, suppressing its RNA helicase activity, and downregulating the AKT/Bcl-2 signaling pathway [4] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9174 mL | 19.5871 mL | 39.1742 mL | |
| 5 mM | 0.7835 mL | 3.9174 mL | 7.8348 mL | |
| 10 mM | 0.3917 mL | 1.9587 mL | 3.9174 mL |