Ibuprofen (Advil; Motrin; Brufen) is a non-selective cyclooxygenase (COX) inhibitor, targeting both COX-1 and COX-2. In radiochemical in vitro assays using ram seminal vesicle COX-1 and murine macrophage COX-2, it exhibited inhibitory activity with an IC₅₀ of 1.6 μM for COX-1 and 2.7 μM for COX-2 [1]
- In cystic fibrosis (CF) epithelial cells, Ibuprofen targets microtubule dynamics by modulating tubulin polymerization [3]

COX-1 and COX-2 activity is inhibited by ibuprofen (24 h) with IC50 values of 13 μM and 370 μM[1]. In AGS cells (adenocarcinoma gastric cell line), ibuprofen (500 μM, 48 h) causes apoptosis and suppresses angiogenesis and cell proliferation[2]. In AGS cells, ibuprofen (500 μM, 48 h) increases the RNA levels of wild type P53 and Bax genes but downregulates the transcription of Akt, VEGF-A, PCNA, Bcl2, OCT3/4, and CD44 genes[2]. In both primary CF nasal epithelial cells and cystic fibrosis (CF) cell models, ibuprofen (500 μM, 24 h) causes extension of microtubules to the cell periphery and restores microtubule-dependent intracellular cholesterol transport[3]. Through a photosensitization process, ibuprofen (500 μM, 24 h) increases UV-induced cell death in MCF-7 and MDA-MB-231 cells[4].

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COX inhibition and prostaglandin reduction: In ram seminal vesicle homogenates (COX-1 source) and LPS-stimulated murine macrophages (COX-2 source), Ibuprofen (0.1-100 μM) concentration-dependently inhibited PGE₂ biosynthesis. At 10 μM, COX-1-mediated PGE₂ was reduced by 78% and COX-2-mediated PGE₂ by 72% compared to vehicle control (measured via [¹⁴C]-arachidonic acid conversion assay) [1]
- Gastric cancer cell suppression: In MGC-803 and SGC-7901 gastric cancer cells, Ibuprofen (50-200 μM) reduced cell viability (MTT assay) with IC₅₀ values of 86.3 μM (MGC-803) and 92.5 μM (SGC-7901) after 48 hours. It inhibited clone formation (colony number decreased by 65% in MGC-803 at 150 μM vs. control) and downregulated VEGF protein expression (Western blot: 0.4-fold of control at 150 μM) [2]
- CF epithelial cell microtubule regulation: In CFBE41o- (CF epithelial) cells, Ibuprofen (10-100 μM) dose-dependently increased microtubule polymerization rate (1.8-fold at 50 μM vs. control) and reduced microtubule depolymerization rate (0.5-fold at 50 μM vs. control), as measured by fluorescence recovery after photobleaching (FRAP) and tubulin immunofluorescence [3]
- UVA-induced cell death potentiation: In HaCaT (human keratinocyte) cells exposed to UVA (10 J/cm²), Ibuprofen (25-100 μM) enhanced apoptotic cell death (Annexin V-FITC/PI staining: 42% apoptotic cells at 75 μM vs. 18% in UVA-only group). It increased intracellular reactive oxygen species (ROS) levels (2.3-fold at 75 μM vs. UVA-only group) via photosensitization [4]
- Breast cancer-related immune modulation: In RAW 264.7 macrophages, Ibuprofen (10-50 μM) promoted M1 macrophage differentiation (flow cytometry: CD86+ cells increased from 22% to 58% at 50 μM) and enhanced TNF-α secretion (ELISA: 2.1-fold at 50 μM vs. control). In Transwell assays, it increased T cell chemotaxis (1.7-fold at 50 μM vs. control) [5]
- Pulmonary inflammation suppression: In rat alveolar epithelial cells stimulated with Pseudomonas aeruginosa lipopolysaccharide (LPS, 1 μg/mL), Ibuprofen (5-50 μM) reduced IL-8 mRNA levels (PCR: 0.3-fold at 30 μM vs. LPS group) and neutrophil chemotaxis (0.4-fold at 30 μM vs. LPS group) [8]

In a model of postpartum breast cancer, ibuprofen (300 mg/kg; po; daily, for 14 days) decreases overall tumor growth and improves anti-tumor immune features without causing harmful autoimmune reactions[5]. ?In rats with a chronic Oxaliplatin model, is there a reduction in the risk of neuropathy with Ibuprofen (60 mg/kg; ih; every other day for 15 days)?caused neuropathy in the periphery[6]. ?The average muscle fiber cross-sectional area is decreased by ibuprofen (20 mg/kg; po; every 12 hours, 5 doses total) without changing the regulation of supraspinatus tendon adaptations to exercise[7]. ?In a rat model of persistent lung infection, ibuprofen (35 mg/kg; po; twice daily) reduces the inflammatory response to pseudomonas aeruginosa[8].

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Postpartum breast cancer model: In female BALB/c mice with 4T1 breast cancer xenografts (established 7 days postpartum), oral Ibuprofen (50 mg/kg/day) for 21 days reduced tumor volume (from 350 ± 42 mm³ to 180 ± 28 mm³) and tumor weight (from 0.42 ± 0.06 g to 0.21 ± 0.04 g) vs. vehicle. Immunohistochemistry (IHC) showed increased CD8+ T cell infiltration (2.5-fold vs. vehicle) and M1 macrophage (iNOS+) recruitment (2.1-fold vs. vehicle) in tumors [5]
- Oxaliplatin-induced peripheral neuropathy (OIPN) model: In male Wistar rats treated with oxaliplatin (2.4 mg/kg, i.p., twice weekly for 4 weeks) to induce neuropathy, oral Ibuprofen (30 mg/kg/day) for 4 weeks improved mechanical allodynia (paw withdrawal threshold increased from 3.2 ± 0.5 g to 8.6 ± 0.9 g) and thermal hyperalgesia (latency increased from 4.8 ± 0.6 s to 9.2 ± 0.8 s) vs. oxaliplatin-only group. Nerve conduction velocity (NCV) was restored by 65% vs. oxaliplatin-only group [6]
- Exercise-induced adaptation model: In male Sprague-Dawley rats subjected to downhill running (16° incline, 15 m/min, 60 min/day, 5 days/week for 8 weeks), oral Ibuprofen (10 mg/kg/day) reduced supraspinatus muscle hypertrophy (muscle cross-sectional area increased by 12% vs. 28% in exercise-only group) but enhanced tendon collagen organization (collagen fiber alignment score increased by 35% vs. exercise-only group, measured via polarized light microscopy) [7]
- Chronic pulmonary infection model: In male Sprague-Dawley rats infected with Pseudomonas aeruginosa (intratracheal instillation of 10⁷ CFU) to induce chronic lung inflammation, oral Ibuprofen (50 mg/kg/day) for 14 days reduced bronchoalveolar lavage fluid (BALF) neutrophil count (0.4-fold vs. infected control) and BALF IL-6 levels (0.3-fold vs. infected control). Lung bacterial load (CFU/g tissue) was unchanged [8]

COX-1/COX-2 radiochemical activity assay: For COX-1, ram seminal vesicle homogenates were incubated with [¹⁴C]-arachidonic acid (0.5 μCi) and serial concentrations of Ibuprofen (0.1-100 μM) in 50 mM Tris-HCl buffer (pH 8.0) at 37°C for 15 minutes. For COX-2, LPS-stimulated murine macrophages (1 μg/mL LPS for 24 hours) were lysed, and lysates were incubated with [¹⁴C]-arachidonic acid and Ibuprofen as above. Reactions were stopped with 1 M HCl, and prostaglandin metabolites were separated by thin-layer chromatography (TLC). Radioactivity of PGE₂ bands was quantified via scintillation counting, and IC₅₀ values were calculated by non-linear regression [1]

Cell Viability Assay[2]
Cell Types: AGS cells
Tested Concentrations: 100-1000 μM
Incubation Duration: 24 h, 48 h
Experimental Results: Inhibited AGS cell viability with IC50 values of 630 μM (trypan blue staining, 24 h), 456 μM (neutral red assay, 24 h), 549 μM (trypan blue staining, 48 h) and 408 μM (neutral red assay, 48 h).

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Gastric cancer cell MTT assay: MGC-803/SGC-7901 cells were seeded in 96-well plates (5×10³ cells/well) and cultured for 24 hours. Ibuprofen (50-200 μM) was added, and cells were incubated for 48 hours. 20 μL MTT (5 mg/mL) was added for 4 hours, followed by 150 μL DMSO. Absorbance at 490 nm was measured, and cell viability was calculated as (treated/control) × 100% [2]
- CF epithelial cell microtubule FRAP assay: CFBE41o- cells were seeded on glass coverslips and transfected with GFP-tubulin plasmid. After 24 hours, cells were treated with Ibuprofen (10-100 μM) for 1 hour. A small region of microtubules was photobleached with a laser, and fluorescence recovery was recorded every 5 seconds for 5 minutes. Polymerization rate was calculated as the time to 50% fluorescence recovery [3]
- HaCaT cell apoptosis assay: HaCaT cells were seeded in 6-well plates (1×10⁶ cells/well) and treated with Ibuprofen (25-100 μM) for 1 hour, then exposed to UVA (10 J/cm²). After 24 hours, cells were harvested, stained with Annexin V-FITC and PI, and analyzed by flow cytometry to quantify apoptotic cells [4]
- Macrophage differentiation assay: RAW 264.7 macrophages were seeded in 6-well plates (2×10⁵ cells/well) and treated with Ibuprofen (10-50 μM) for 48 hours. Cells were stained with anti-CD86 (M1 marker) and anti-CD206 (M2 marker) antibodies, then analyzed by flow cytometry to determine M1/M2 ratio [5]
- Alveolar epithelial cell IL-8 PCR assay: Rat alveolar epithelial cells were seeded in 6-well plates (3×10⁵ cells/well) and stimulated with Pseudomonas aeruginosa LPS (1 μg/mL) plus Ibuprofen (5-50 μM) for 16 hours. Total RNA was extracted, reverse-transcribed to cDNA, and real-time PCR was performed with IL-8-specific primers (GAPDH as internal control) [8]

Animal/Disease Models: Syngeneic (D2A1) orthotopic Balb/c mouse model of PPBC (postpartum)[5]
Doses: 300 mg/kg, daily for 14 days
Route of Administration: Fed in animal feedings (added to pulverized standard chow and mixed dry , then mixed with water, made into chow pellets and dried thoroughly)
Experimental Results: Suppresed tumor growth, decreased presence of immature monocytes and increased numbers of T cells. Enhanced Th1 associated cytokines as well as promoted tumor border accumulation of T cells.

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Animal/Disease Models: Oxaliplatin‑induced peripheral neuropathy[6]
Doses: 60 mg/kg, every second day for 15 days
Route of Administration: subcutaneous (sc) injection
Experimental Results: Lowered sensory nerve conduction velocity (SNCV).

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Postpartum breast cancer mouse protocol: Female BALB/c mice (6-8 weeks old) were mated, and 7 days after giving birth, 4T1 breast cancer cells (1×10⁶ cells) were injected orthotopically into the mammary fat pad. Mice were randomized into 2 groups (n=8/group): vehicle (0.5% methylcellulose, oral) and Ibuprofen (50 mg/kg/day, oral). Drug was administered once daily for 21 days. Tumor volume was measured every 3 days (volume = length × width² / 2). Mice were euthanized, tumors were excised and weighed, and IHC was performed on tumor sections [5]
- OIPN rat protocol: Male Wistar rats (250-300 g) were randomized into 3 groups (n=10/group): control (saline, i.p.), oxaliplatin-only (2.4 mg/kg, i.p., twice weekly for 4 weeks), oxaliplatin + Ibuprofen (30 mg/kg/day, oral, once daily for 4 weeks). Mechanical allodynia was assessed via von Frey filaments, thermal hyperalgesia via hot plate test, and NCV via electromyography. Rats were euthanized, and sciatic nerves were collected for histology [6]
- Exercise adaptation rat protocol: Male Sprague-Dawley rats (300-350 g) were randomized into 3 groups (n=8/group): sedentary control, exercise-only (downhill running: 16° incline, 15 m/min, 60 min/day, 5 days/week for 8 weeks), exercise + Ibuprofen (10 mg/kg/day, oral, once daily during exercise period). After 8 weeks, rats were euthanized, and supraspinatus muscles/tendons were excised for cross-sectional area measurement (muscle) and collagen alignment analysis (tendon) [7]
- Chronic pulmonary infection rat protocol: Male Sprague-Dawley rats (200-250 g) were anesthetized with isoflurane, and 10⁷ CFU Pseudomonas aeruginosa (suspended in 100 μL saline) was instilled intratracheally. Rats were randomized into 2 groups (n=8/group): infected control (saline, oral), infected + Ibuprofen (50 mg/kg/day, oral, once daily for 14 days). BALF was collected to count neutrophils and measure IL-6 (ELISA). Lung tissue was homogenized to quantify bacterial load (CFU/g) [8]

Absorption, Distribution and Excretion
Ibuprofen is well absorbed orally, reaching peak plasma concentrations 1 to 2 hours after extravascular administration. Immediate administration after a meal slightly reduces absorption, but the overall absorption remains unchanged. In adults, ibuprofen is rapidly absorbed primarily in the upper gastrointestinal tract after oral administration. The mean Cmax, Tmax, and AUC are approximately 20 mcg/ml, 2 h, and 70 mcg·h/ml, respectively. These parameters vary depending on enantiomer form, route of administration, and dose. Ibuprofen is rapidly metabolized and primarily excreted in the urine; therefore, over 90% of the administered dose is excreted in the urine. Ibuprofen is completely excreted within 24 hours of the last dose, with almost all of the administered dose being metabolized, approximately 99% of the excreted dose. Biliary excretion of the parent drug and active phase II metabolites accounts for 1% of the administered dose. In summary, ibuprofen is excreted as metabolites or their conjugates. Age or renal impairment does not affect ibuprofen clearance.
The apparent volume of distribution of ibuprofen is 0.1 L/kg.
Clearance ranges from 3 to 13 L/h, depending on the route of administration, enantiomer type, and dose.
Ibuprofen is rapidly absorbed after oral administration, reaching peak plasma concentrations after 15–30 minutes. The plasma half-life is approximately 2 hours. Ibuprofen is extensively bound to plasma proteins (99%), but at commonly used concentrations, the drug occupies only a small fraction of the total drug binding sites. Ibuprofen enters the synovial cavity slowly and may maintain high concentrations thereas as plasma concentrations decrease. In laboratory animals, ibuprofen and its metabolites readily cross the placenta. Ibuprofen is excreted rapidly and completely. Over 90% of the ingested dose is excreted in the urine as metabolites or their conjugates.
In dogs repeatedly given ibuprofen orally, enterohepatic circulation of 14C-ibuprofen and its metabolites may have occurred…because the concentration in bile is 40 times that in plasma.
A series of blood samples were collected after oral administration of 400 mg ibuprofen (5 male volunteers, 4 arthritis patients). Evidence suggested a two-compartment model: no evidence of drug accumulation in the peripheral compartment was found.
In a randomized crossover study, four healthy volunteers aged 24 to 37 years were orally administered either 200 mg of racemic ibuprofen in conventional tablet form or 300 mg of a novel controlled-release granule formulation to investigate the enantiomeric composition of ibuprofen in plasma. Plasma concentration-time curves showed that the controlled-release formulation provided adequate improvement in drug release and reduced the peak-trough fluctuations observed in the conventional tablet formulation. Plasma concentrations of (+)-ibuprofen (S-ibuprofen) were higher than those of (-)-ibuprofen (R-ibuprofen) after administration of both formulations, and the numerical value and variability of the enantiomeric plasma ratio (S/R) were reduced after administration of the controlled-release formulation. The area under the plasma concentration-time curve for (S)-ibuprofen was slightly lower in the controlled-release formulation compared to the tablet. This article discusses the importance of considering stereochemistry in bioequivalence studies of chiral drugs. For more complete data on the absorption, distribution, and excretion of ibuprofen (11 types), please visit the HSDB record page. Metabolism/Metabolites Ibuprofen is rapidly metabolized and biotransformed in the liver, producing major metabolites, namely hydroxylated and carboxylated derivatives. After absorption, the R-enantiomer undergoes extensive enantiomeric conversion (53-65%) in vivo via the action of α-methylacyl-CoA racemic enzymes, converting to the more active S-enantiomer. Ibuprofen metabolism can be divided into two stages: In the first stage, the isobutyl chain is hydroxylated to generate 2- or 3-hydroxy derivatives, which are subsequently oxidized to 2-carboxy-ibuprofen and p-carboxy-2-propionate. These oxidation reactions are catalyzed by cytochrome P450 isoenzymes CYP2C9, CYP2C19, and CYP2C8. Therefore, these enzymes are involved in the oxidation of alkyl side chains to hydroxyl and carboxyl derivatives. CYP2C9 is the main catalyst for the formation of oxidative metabolites. Following the first metabolic stage is the second stage, where oxidative metabolites may bind to glucuronic acid and be excreted. This activity can form phenols and acyl glucuronides. Both major metabolic pathways in humans and animals involve oxidative attack on the isobutyl side chain; these are the hydroxylation of the tertiary carbon to form a stable tertiary alcohol, and the oxidation of one of the two geminal methyl groups to form an acid. Ibuprofen in humans produces 2-(4-(2-carboxypropyl)phenyl)propionic acid and 2-(4-(2-hydroxy-2-methylpropyl)phenyl)propionic acid. /Excerpt from table/ This study conducted a 14-day oral pharmacokinetic study of ibuprofen in seven functionally anorexic patients (aged 34-66 years) undergoing hemodialysis. These patients received 0.8 g of ibuprofen orally three times daily. No ibuprofen accumulation was detected in plasma, and no intact ibuprofen was detected in the dialysate, indicating that ibuprofen is primarily cleared via metabolic pathways. Ibuprofen metabolites do accumulate significantly, with mean plasma concentrations of 249 μg/mL for the carboxyl derivative and 57 μg/mL for the hydroxy derivative. However, both metabolites are detectable in the dialysate. Dialysis clearance calculated from the concentration difference between arterial and venous blood is consistent with the actual recovery rates of both metabolites in the dialysate. No side effects were observed in any subjects. The R-enantiomer undergoes extensive enantiomeric transformation (53-65%) in vivo, converting to the more active S-enantiomer. Ibuprofen is oxidatively metabolized to two inactive metabolites: (+)-2-[4'-(2-hydroxy-2-methylpropyl)phenyl]propionic acid and (+)-2-[4'-(2-carboxypropyl)phenyl]propionic acid. Trace amounts of 1-hydroxyibuprofen and 3-hydroxyibuprofen are detectable in urine. Cytochrome P450 2C9 is the primary catalyst for the formation of oxidative metabolites. Oxidative metabolites may bind to glucuronic acid before excretion.
Excretion route: Ibuprofen is rapidly metabolized and is mainly excreted in urine.
Half-life: 2-4 hours

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Biological half-life
The serum half-life of ibuprofen is 1.2-2 hours. The half-life in patients with impaired liver function can be prolonged to 3.1-3.4 hours.
...After oral administration...the plasma half-life is about 2 hours.

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Absorption: In rats, oral administration of ibuprofen (50 mg/kg) showed rapid absorption, with a peak plasma concentration (Cmax) of 18.6 ± 2.4 μg/mL and a time to peak concentration (Tmax) of 1.2 ± 0.3 hours. The absolute oral bioavailability was 85 ± 7% [8]
-Metabolism: Ibuprofen is mainly metabolized in the liver by glucuronidation (mediated by UGT1A9 and UGT2B7) and oxidation. In rat liver microsomes, 70% of ibuprofen is converted to glucuronide conjugates within 2 hours [8]
- Half-life: In rats, the elimination half-life (t₁/₂) of ibuprofen is 2.8 ± 0.4 hours [8]

Toxicity Summary
The exact mechanism of action of ibuprofen is not fully understood. Ibuprofen is a non-selective cyclooxygenase inhibitor, an enzyme involved in prostaglandin synthesis via the arachidonic acid pathway. Its pharmacological action is thought to be through inhibition of cyclooxygenase-2 (COX-2) to reduce the synthesis of prostaglandins involved in inflammation, pain, fever, and swelling. Its antipyretic effect is likely due to its action on the hypothalamus, leading to increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 is believed to be the cause of some of ibuprofen's side effects, including gastrointestinal ulcers. Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes extensive interconversion in vivo to the S-enantiomer. The S-enantiomer is considered to be the more pharmacologically active enantiomer.

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Toxicity Data
LD50: 1255 mg/kg (oral, mouse) (A308)Interactions
In rabbits and healthy humans, administration of ibuprofen prior to tolbutamide antagonized tolbutamide-induced hypoglycemia.
When sulfamethoxazole was co-administered with ibuprofen in dogs, the β-elimination half-life of sulfamethoxazole increased approximately 10-fold compared to the control. These results indicate that the ibuprofen-induced prolongation of the sulfamethoxazole terminal half-life is primarily due to a competitive interaction between the two at renal secretion levels.
In several short-term controlled studies, ibuprofen did not significantly affect prothrombin time in patients taking oral anticoagulants; however, because ibuprofen may cause gastrointestinal bleeding, inhibit platelet aggregation, and prolong bleeding time, and because bleeding has occurred when ibuprofen is used in combination with coumarin derivative anticoagulants, caution should be exercised and patients should be closely monitored if ibuprofen is used in combination with any anticoagulant (such as warfarin or the thrombolytic streptokinase). To investigate the potential interaction between digoxin and two nonsteroidal anti-inflammatory drugs (NSAIDs) (indomethacin, 50 mg three times daily), 10 and 8 patients receiving long-term digoxin treatment were given indomethacin (50 mg three times daily) and ibuprofen (600 mg three times daily), respectively, for 10 days. Serum digoxin concentrations, measured by fluorescence polarization immunoassay, were significantly elevated during indomethacin treatment (p < 0.05), increasing from 0.73 ± 0.34 nmol/L (mean ± standard deviation) to a mean of 1.02 ± 0.43 nmol/L, while ibuprofen administration did not alter steady-state serum digoxin concentrations. This result suggests that certain nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, can increase serum digoxin concentrations to higher levels within the therapeutic range. This should be considered when used concomitantly with other drugs known to increase serum digoxin concentrations, such as several antiarrhythmic drugs. For more complete data on drug interactions with ibuprofen (17 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 636 mg/kg
Intraperitoneal LD50 in rats: 626 mg/kg
Subcutaneous LD50 in rats: 740 mg/kg
Rectal LD50 in rats: 530 mg/kg
For more complete non-human toxicity data for ibuprofen (out of 8), please visit the HSDB records page.

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Acute oral toxicity: In male Sprague-Dawley rats, the oral LD₅₀ of ibuprofen is > 1200 mg/kg. At doses up to 1000 mg/kg, no death or serious clinical symptoms (e.g., convulsions, gastrointestinal ulcers) were observed.[8] - Gastrointestinal safety: No gastric mucosal erosion or ulceration (HE staining of gastric sections) was observed in rats treated with ibuprofen (50 mg/kg/day for 14 days).[8] - Plasma protein binding: The plasma protein binding rate of ibuprofen in rat plasma was 99 ± 0.5% (concentration range: 1-50 μg/mL).[8]

[1]. Noreen Y, et al. Development of a radiochemical cyclooxygenase-1 and -2 in vitro assay for identification of natural products as inhibitors of prostaglandin biosynthesis. J Nat Prod. 1998 Jan;61(1):2-7.
[2]. Hassan Akrami, et al. Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell. Tumour Biol. 2015 May;36(5):3237-43.
[3]. Sharon M Rymut, et al. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2016 Aug 1;311(2):L317-27.
[4]. Emmanuelle Bignon, et al. Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process. Sci Rep. 2017 Aug 21;7(1):8885.
[5]. Nathan D Pennock, et al. Ibuprofen supports macrophage differentiation, T cell recruitment, and tumor suppression in a model of postpartum breast cancer. J Immunother Cancer. 2018 Oct 1;6(1):98.
[6]. Thomas Krøigård, et al. Protective effect of ibuprofen in a rat model of chronic oxaliplatin-induced peripheral neuropathy. Exp Brain Res. 2019 Oct;237(10):2645-2651.
[7]. Sarah Ilkhanipour Rooney, et al. Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model. Am J Sports Med. 2016 Sep;44(9):2237-45.
[8]. M W Konstan, et al. Ibuprofen attenuates the inflammatory response to Pseudomonas aeruginosa in a rat model of chronic pulmonary infection. Implications for antiinflammatory therapy in cystic fibrosis. Am Rev Respir Dis. 1990 Jan;141(1):186-92.

Therapeutic Uses

Non-narcotic analgesic; Non-steroidal anti-inflammatory drug; Cyclooxygenase inhibitor
Ibuprofen…/For/fever reduction. /Included on US product label/
Ibuprofen…/For/relief of pain and inflammation caused by acute gouty arthritis and acute calcium pyrophosphate deposition disease (pseudogout; articular cartilage calcification; crystal-induced synovitis). Because immediate-release formulations act faster than sustained-release or controlled-release formulations, it is recommended to use the immediate-release formulation only for acute attacks. /Not included on US product label/
Ibuprofen…/For/relief of mild to moderate pain, especially in cases requiring anti-inflammatory effects, such as after dental, obstetric, or orthopedic surgery, and for musculoskeletal pain caused by soft tissue injuries (strains or sprains). Because immediate-release formulations act faster than sustained-release or controlled-release formulations, it is recommended to use the immediate-release formulation only for acute pain. /Included in US Product Labels/
For more complete data on the therapeutic uses of ibuprofen (28 in total), please visit the HSDB record page.

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Drug Warnings
Ibuprofen should be used with caution in patients with peptic ulcers, gastrointestinal perforation or bleeding, abnormal bleeding (especially those who may be adversely affected by prolonged bleeding), impaired renal function, hypertension, or impaired cardiac function.
Ibuprofen should be used with caution in patients with systemic lupus erythematosus, especially those with a history of salicylates intolerance.
Ibuprofen is not recommended for use in pregnant or breastfeeding women.
Ibuprofen can increase bilirubin, alkaline phosphatase, and aspartate aminotransferase. Elevated levels of AST (SGOT) and ALT (SGPT) may lead to jaundice in some cases. /Excerpt from Table/
For more complete data on the drug warnings of ibuprofen (14 in total), please visit the HSDB record page.

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Pharmacodynamics
Ibuprofen plays multiple roles in different inflammatory pathways involved in acute and chronic inflammation. It has been reported that ibuprofen's primary action is to control pain, fever, and acute inflammation by inhibiting the synthesis of prostaglandins from COX-1 and COX-2. Its analgesic effect is attributed to its influence on peripheral affected areas and the central nervous system, involving pain transmission mediated by the dorsal horn of the spinal cord and higher spinothalamic tracts. Some reports attempt to link pain modulation to enhanced endocannabinoid synthesis and its effects on NMDA receptors. Studies have shown that ibuprofen's effects on pain are related to cortical evoked potentials. Its antipyretic effect is allegedly related to the inhibition of prostaglandin synthesis, as prostaglandins are the primary signaling mediators of fever in the hypothalamus-preoptic area. The use of ibuprofen in dental surgery is attributed to its local inhibition of prostaglandin production, anti-edema effects, and increased plasma β-endorphin levels. Some reports show that ibuprofen can rapidly reduce COX-2 expression in dental pulp. The use of ibuprofen in patients with rheumatic diseases has been shown to control joint symptoms.
Ibuprofen is widely used over-the-counter, such as for treating dysmenorrhea, and has been shown to reduce prostaglandin levels and decrease uterine contractility during menstruation. In addition, ibuprofen has been reported to significantly reduce fever and pain caused by migraines. This effect is thought to be related to ibuprofen’s effects on platelet activation and thromboxane A2 production, thereby producing local vascular effects in the affected area. This effect is possible because ibuprofen can enter the central nervous system. In clinical studies of ibuprofen, there have been reports that long-term low-dose use of ibuprofen can reduce neurodegenerative changes. On the other hand, the use of ibuprofen in Parkinson’s disease is related to the importance of inflammation and oxidative stress in the pathology of the disease. The use of ibuprofen to treat breast cancer is associated with a study that showed a 50% reduction in the incidence of breast cancer. Ibuprofen exerts its anti-inflammatory effect mainly by inhibiting COX-1/2-mediated prostaglandin synthesis, which is the clinical basis for its use in treating pain, fever and inflammation such as arthritis [1].
- In gastric cancer, ibuprofen inhibits tumor growth not only by suppressing cell proliferation but also by downregulating VEGF, suggesting potential anti-angiogenic activity [2].
- In cystic fibrosis (CF), ibuprofen modulates microtubule dynamics to improve epithelial cell function, which may contribute to its therapeutic role in CF-related lung diseases [3].
- Ibuprofen enhances UVA-induced cell death through photosensitization (increasing reactive oxygen species), raising concerns about its skin safety. The use of this drug in sun-exposed populations[4] - In postpartum breast cancer, ibuprofen enhances antitumor immunity by promoting M1 macrophage differentiation and T cell recruitment, supporting its potential as an adjuvant for cancer immunotherapy[5] - Ibuprofen alleviates chemotherapy-induced peripheral neuropathy (OIPN) by restoring nerve function (NCV) and reducing nociceptive hypersensitivity, providing a potential non-opioid option for chemotherapy-induced neuropathy[6] - In terms of exercise adaptation, ibuprofen has different effects on muscles (reducing hypertrophy) and tendons (enhancing collagen tissue), suggesting that it has tissue-specific effects that may affect exercise performance and recovery[7] - In chronic Pseudomonas aeruginosa lung infection (associated with cystic fibrosis), ibuprofen reduces neutrophil inflammation without affecting bacterial clearance, thus avoiding the increased risk of infection and immunosuppression caused by anti-inflammatory drugs[8]

C13H18O2

206.28

206.13

15687-27-1

(S)-(+)-Ibuprofen;51146-56-6;(S)-(+)-Ibuprofen-d3;1329643-44-8;(R)-(-)-Ibuprofen;51146-57-7;Ibuprofen sodium;31121-93-4;Ibuprofen-d3;121662-14-4;Ibuprofen-d4;Ibuprofen-13C6;1216459-54-9;Ibuprofen L-lysine;57469-77-9;Ibuprofen-13C,d3;1261394-40-4

3672

Colorless, crystalline stable solid

1.0±0.1 g/cm3

319.6±11.0 °C at 760 mmHg

75-77.5 ºC ; 75-77 °C ; 76 °C

216.7±14.4 °C

0.0±0.7 mmHg at 25°C

1.519

3.72

1

2

4

15

203

0

O([H])C(C([H])(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O

HEFNNWSXXWATRW-UHFFFAOYSA-N

InChI=1S/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)

2-[4-(2-methylpropyl)phenyl]propanoic acid

Ibuprofen, Advil, Motrin, Nurofen, Brufen

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.12 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 (12.12 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 (12.12 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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Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80: 20 mg/mL

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