Primary target: Cyclooxygenase-2 (COX-2) (IC50: ~0.7 nM for human recombinant COX-2; IC50 for COX-1: ~1000 nM, showing high selectivity for COX-2 over COX-1) [1]
- Downstream regulatory targets involved in retinal neovascularization: Vascular Endothelial Growth Factor (VEGF) (indirectly inhibited via COX-2 downregulation) [2]
- Synergistic target with gefitinib: COX-2 (no new direct targets identified; synergism involves COX-2 and EGFR pathways, with Rofecoxib targeting COX-2) [3]

In human osteosarcoma cells and Chinese hamster ovary cells, rofecoxib (MK-0966) has IC50s of 26 and 18 nM for human COX-2, respectively. It has a 1000-fold selectivity for COX-2 over COX-1 (IC50 >50 μM in U937 cells and >15 μM in Chinese hamster ovary cells). Rofecoxib is a strong and oral active inhibitor of COX-2. Rofecoxib suppresses purified human COX-1 in a non-time-dependent way that is only visible at extremely low substrate concentrations (IC50=26 μM at 0.1 μM arachidonic acid concentration), whereas it time-dependently inhibits purified human recombinant COX-2 (IC50=0.34 μM). When it comes to the suppression of COX-1-derived thromboxane B(2) synthesis after blood coagulation, rofecoxib has a higher IC50 value of 18.8 ± 0.9 μM than lipopolysaccharide-induced, COX-2-derived PGE(2) synthesis [1]. Cell proliferation is induced by ropecoxib (36 μM) at 68% in MPP89, 58% in Ist-Mes-1, and 40% in Ist-Mes-2. The survival rates of MSTO-211H and NCI-H2452 after receiving 36 μM of rofecoxib are 97% and 90%, respectively. In Ist-Mes-1, Ist-Mes-2, and MPP89 cell lines, ropecoxib (36 μM) reduces the levels of COX-2 and mRNA[3].

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Enzymatic activity: Rofecoxib potently inhibited COX-2-mediated prostaglandin E2 (PGE2) production in human recombinant COX-2 assays (IC50: 0.7 nM) and in LPS-stimulated human monocytes (IC50: ~1.8 nM), while showing minimal inhibition of COX-1-mediated PGE2 production in sheep seminal vesicle microsomes (IC50: >1000 nM) [1]
- Retinal cell activity: Rofecoxib (1, 5, 10 μM) reduced VEGF mRNA and protein expression in hypoxia-induced retinal pigment epithelial (RPE) cells; it also inhibited proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) in a concentration-dependent manner, with maximum inhibition at 10 μM [2]
- Mesothelioma cell activity: Rofecoxib (IC50: ~15 μM for H2052 cells, ~20 μM for H2452 cells) inhibited proliferation of human mesothelioma cell lines; when combined with gefitinib (IC50: ~5 μM for H2052 cells), it showed synergistic antiproliferative effects (combination index <1), increased caspase-3 activation, and reduced COX-2 and phospho-EGFR protein levels [3]

In mouse models, rofecoxib potently suppresses the following: lipopolysaccharide-induced pyresis (ID50=0.24 mg/kg), carrageenan-induced paw edema (ID50=1.5 mg/kg), and adjuvant-induced arthritis (ID50=0.74 mg/kg/day). In rats, rofecoxib also prevents the degradation of bone and cartilage caused by adjuvants. Ropecoxib has no effect at doses up to 200 mg/kg/day for five days in a 51Cr excretion experiment used to assess gastrointestinal integrity in either rats or squirrel monkeys[1]. In mice, the blood vessels connected to the internal limiting membrane (ILM) are diminished by rofecoxib (15 mg/kg, ip). In ROP mice, Rofecoxib also greatly reduces the expressions of the COX-2 and VEGF proteins, as well as the COX-2 and VEGF mRNAs[2].

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Anti-inflammatory activity: In rats with carrageenan-induced paw edema, oral administration of Rofecoxib (1, 3, 10 mg/kg) reduced paw volume in a dose-dependent manner, with 10 mg/kg showing ~80% inhibition at 4 hours post-administration; it also inhibited adjuvant-induced arthritis in rats (10 mg/kg, oral) by reducing paw swelling and joint damage [1]
- Retinal neovascularization inhibition: In a mouse oxygen-induced retinopathy (OIR) model (75% oxygen from P7 to P12, then room air), oral Rofecoxib (5, 10 mg/kg/day) from P12 to P17 reduced the area of retinal neovascularization by ~35% (5 mg/kg) and ~55% (10 mg/kg) compared to vehicle; it also decreased VEGF and COX-2 protein levels in retinal homogenates [2]
- Antitumor synergism: In nude mice bearing H2052 mesothelioma xenografts, oral Rofecoxib (10 mg/kg/day) combined with gefitinib (25 mg/kg/day) significantly inhibited tumor growth (tumor volume reduction: ~60%) compared to Rofecoxib alone (~20% reduction) or gefitinib alone (~25% reduction); no significant increase in body weight loss was observed in the combination group [3]

COX-2 activity assay: Human recombinant COX-2 was incubated with arachidonic acid (substrate) and various concentrations of Rofecoxib (0.1-100 nM) at 37°C for 10 minutes. PGE2 (product of COX-2) was measured using a competitive radioimmunoassay (RIA) with a specific anti-PGE2 antibody. The IC50 was calculated by plotting PGE2 production against Rofecoxib concentration and fitting to a four-parameter logistic model [1]
- COX-1 activity assay: Sheep seminal vesicle microsomes (source of COX-1) were incubated with arachidonic acid and Rofecoxib (100 nM-10 μM) at 37°C for 10 minutes. PGE2 was quantified via RIA, and the IC50 for COX-1 was determined as described for COX-2 [1]

LPS-stimulated monocyte assay: Human peripheral blood monocytes were isolated and cultured, then stimulated with LPS (1 μg/mL) to induce COX-2 expression. Cells were treated with Rofecoxib (0.1-100 nM) for 24 hours, and culture supernatants were collected to measure PGE2 via RIA. Cell viability was assessed by trypan blue exclusion to ensure no cytotoxicity at the tested concentrations [1]
- Retinal cell assays: 1) RPE cells were cultured under hypoxia (1% O2) for 24 hours with Rofecoxib (1-10 μM); total RNA was extracted, and VEGF mRNA was quantified by real-time PCR (using GAPDH as internal control). 2) HRMECs were seeded on Matrigel, treated with Rofecoxib (1-10 μM) plus VEGF (50 ng/mL), and tube formation was counted under a microscope after 6 hours. 3) Western blot analysis was performed on RPE cell lysates to detect COX-2 and VEGF protein levels (using β-actin as loading control) [2]
- Mesothelioma cell assays: 1) H2052/H2452 cells were seeded in 96-well plates, treated with Rofecoxib (0.1-100 μM) alone or with gefitinib (0.1-50 μM) for 72 hours, and cell viability was measured by MTT assay. 2) For apoptosis detection, cells were treated with the drug combination for 48 hours, stained with annexin V-FITC/PI, and analyzed by flow cytometry. 3) Western blot was used to detect COX-2, phospho-EGFR, and cleaved caspase-3 protein levels in treated cells [3]

Dissolved in 80% PEG 200 in distilled water; 0.1, 0.3, 1.0, and 3.0 mg/kg/day; p.o. administration
Rat adjuvant-induced arthritis (AIA) model

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Rat anti-inflammatory models: 1) Carrageenan-induced paw edema: Male Sprague-Dawley rats (200-250 g) received a subplantar injection of carrageenan (1% in saline) into the right hind paw. Rofecoxib was suspended in 0.5% methylcellulose and administered orally 1 hour before carrageenan injection at doses of 1, 3, or 10 mg/kg. Paw volume was measured using a plethysmometer at 0, 2, 4, and 6 hours post-carrageenan. 2) Adjuvant-induced arthritis: Rats received a subcutaneous injection of Freund’s complete adjuvant (0.1 mL) into the left hind paw. Rofecoxib (10 mg/kg, oral) was administered daily from day 1 to day 21, and paw swelling was measured twice weekly [1]
- Mouse OIR model: C57BL/6 mice (P7 pups with dams) were exposed to 75% oxygen for 5 days (P7-P12), then returned to room air to induce retinal neovascularization. Rofecoxib was dissolved in DMSO (final concentration <0.1%) and diluted in saline, then administered orally via gavage at 5 or 10 mg/kg/day from P12 to P17 (once daily). On P17, mice were euthanized, eyes were enucleated, and retinas were isolated for immunofluorescence staining (using isolectin B4 to label blood vessels) [2]
- Mesothelioma xenograft model: Female nude mice (6-8 weeks old) were subcutaneously injected with H2052 cells (5×10^6 cells in 0.2 mL PBS/matrigel) into the right flank. When tumors reached ~100 mm³, mice were randomized into 4 groups: vehicle (0.5% methylcellulose, oral), Rofecoxib (10 mg/kg, oral), gefitinib (25 mg/kg, oral), or combination. Drugs were administered daily for 21 days. Tumor volume was measured every 3 days using calipers (volume = length × width² / 2), and body weight was recorded weekly [3]

Absorption, Distribution and Excretion
The mean oral bioavailability of rofecoxib at the recommended therapeutic doses of 12.5 mg, 25 mg, and 50 mg is approximately 93%. Of the radiolabeled rofecoxib dose, approximately 72% is excreted in the urine as metabolites and 14% is excreted unchanged in the feces. Time to peak concentration: approximately 2 to 3 hours. At steady state, the apparent volume of distribution after administration of 12.5 mg and 25 mg doses is approximately 91 L and 86 L, respectively. The mean oral bioavailability at the recommended dose is 93%. Within the clinical dose range, peak plasma concentration is approximately proportional to the area under the plasma concentration-time curve. For more complete data on absorption, distribution, and excretion of rofecoxib (11 items in total), please visit the HSDB record page. Metabolism/Metabolites Hepatic metabolism. The metabolism of rofecoxib is primarily mediated by the reductive action of cytoplasmic enzymes. The main metabolites are cis- and trans-dihydro derivatives of rofecoxib, accounting for approximately 56% of the radioactive recovery in urine. An additional 8.8% of the dose is recovered as glucuronides of hydroxyl derivatives, products of oxidative metabolism. The biotransformation of rofecoxib and its metabolites in humans is reversible to a limited extent (<5%). These metabolites do not possess COX-1 or COX-2 inhibitory activity. Cytochrome P450 plays a minor role in the metabolism of rofecoxib. This study investigated the metabolism of rofecoxib (a potent and selective cyclooxygenase-2 inhibitor) in vitro using human liver subcellular components. The biotransformation of rofecoxib is highly dependent on the subcellular components and the redox system used. In hepatic microsomal incubation, rofecoxib primarily oxidizes to 5-hydroxyrofecoxib via NADPH-dependent oxidation; while in cytoplasmic incubation, rofecoxib primarily oxidizes to 3,4-dihydrohydroxy acid metabolites via NADPH-dependent reduction. Metabolites from both oxidative and reductive pathways were observed in S9 fraction incubation. Unlike microsomal incubation, the oxidation of rofecoxib to 5-hydroxyrofecoxib in S9 fraction follows two pathways: one NADPH-dependent and the other NAD+ (non-cytochrome P450), with the latter accounting for approximately 40% of the total activity. The generated 5-hydroxyrofecoxib undergoes NADPH-dependent reduction (“reverse reduction”) upon incubation with hepatic cytoplasmic fractions, regenerating rofecoxib. Upon incubation with dialysis hepatic cytoplasm, rofecoxib was observed to undergo net hydration to 3,4-dihydro-5-hydroxyrofecoxib; however, in the presence of NADPH, a 3,4-dihydrohydroxy acid derivative was generated. Although 3,4-dihydro-5-hydroxyrofecoxib can be reduced to 3,4-dihydrohydroxy acid in the presence of NADPH via the cytosol, the former does not appear to be an intermediate in the overall reductive metabolic pathway of rofecoxib. Net reductive metabolism was superior to oxidative metabolism after incubation with the S9 component for more than 2 hours. These in vitro results are consistent with previous studies on the metabolism of rofecoxib in humans and provide valuable insights into the mechanisms of this drug's complex metabolism. The metabolism of rofecoxib is primarily mediated by the reductive action of cytosol enzymes. Its major metabolites are the cis- and trans-dihydro derivatives of rofecoxib, accounting for approximately 56% of the radioactive recovery in urine. Another 8.8% of the dose is recovered as glucuronides of the hydroxy derivatives, which are products of oxidative metabolism. The biotransformation of rofecoxib and its metabolites in humans is reversible to a limited extent (<5%). These metabolites do not possess COX-1 or COX-2 inhibitory activity. Known metabolites of rofecoxib include 5-hydroxyrofecoxib.

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Biological half-life
17 hours
Approximately 17 hours.

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Oral absorption: In rats, oral administration of rofecoxib (10 mg/kg) showed rapid absorption, with a peak plasma concentration (Cmax) of approximately 2.5 μg/mL, reached at 1 hour (Tmax). Oral bioavailability was approximately 90%, compared to intravenous administration [1]
-Plasma protein binding: In human plasma, rofecoxib exhibits high protein binding (approximately 97%), primarily binding to albumin; the binding rate is concentration-independent in the concentration range of 0.1–10 μg/mL [1]
-Elimination: In dogs, the plasma half-life (t1/2) of rofecoxib is approximately 11 hours; it is primarily eliminated through metabolism (oxidation and glucuronidation), with less than 5% of the dose excreted unchanged in the urine [1]

Hepatotoxicity
In thousands of clinical studies involving at least 3 months of treatment, the incidence of serum ALT elevations exceeding three times the upper limit of normal was 1.8% in the rofecoxib treatment group, compared to 0.3% in the placebo group and 0.1-0.4% in other commonly used nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, rofecoxib-induced ALT elevations are uncommon and usually clinically insignificant, resolving spontaneously with continued use. In rare cases, rofecoxib can cause clinically significant, symptomatic drug-induced liver injury, accompanied by jaundice. The pattern of elevated liver enzymes is typically cholestatic or mixed (Case 1), but hepatocellular injury has also been reported. The latency period for liver injury varies greatly, ranging from weeks to years, but usually appears within 1 to 12 weeks of starting treatment. Autoimmune and immune hypersensitivity features are uncommon. Probability score: C (likely a rare cause of clinically significant liver injury).

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Protein Binding
87%
Drug Interactions
Rifampin co-administration with rofecoxib may reduce rofecoxib plasma concentrations by 50%;….
In patients receiving methotrexate 7.5 to 15 mg/week, daily administration of rofecoxib 75 mg for 10 days increased plasma methotrexate concentrations by 23%; the effect of the recommended dose of rofecoxib is unclear; therefore, monitoring for methotrexate toxicity is recommended.
Aspirin co-administration with rofecoxib may increase the risk of gastrointestinal ulcers or gastrointestinal complications.
In elderly patients, co-administration of rofecoxib with antacids containing calcium carbonate, aluminum, or magnesium reduced the area under the plasma concentration-time curve (AUC) by 13% and 8%, respectively; both antacids reduced peak plasma concentrations of rofecoxib by approximately 20%.
For more complete data on rofecoxib interactions (14 in total), please visit the HSDB record page.

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Gastrointestinal toxicity: No significant gastric mucosal damage was observed in rats treated with rofecoxib (10, 30 mg/kg/day, orally) for 28 days; in contrast, indomethacin (a non-selective COX inhibitor) caused severe gastric ulcers at a dose of 5 mg/kg/day[1]
- Hepatotoxicity: In mice, no significant changes in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels were observed after 14 days of treatment with rofecoxib (orally, at doses up to 30 mg/kg/day)[2]
- Combination therapy toxicity: In a mesothelioma xenograft model, rofecoxib (10 mg/kg/day) in combination with gefitinib (25 mg/kg/day) did not result in a significant increase in mortality or organ toxicity (assessed by histopathological evaluation of the liver, kidneys and spleen) compared to the monotherapy group[3]

[1]. Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther. 1999 Aug;290(2):551-60.

[2]. Rofecoxib inhibits retinal neovascularization via down regulation of cyclooxygenase-2 and vascular endothelial growth factor expression. Clin Exp Ophthalmol. 2015 Jul;43(5):458-65.

[3]. Synergistic effect of gefitinib and rofecoxib in mesothelioma cells. Mol Cancer. 2010 Feb 2;9:27.

Rofecoxib is a butenolactone compound with the structure furan-2(5H)-one, substituted with a phenyl group at position 3 and a p-(methanesulfonyl)phenyl group at position 4. It is a selective cyclooxygenase-2 inhibitor, used to treat osteoarthritis from 1999 to 2004, but was withdrawn from the market due to concerns about its potential to increase the risk of heart attack and stroke. Rofecoxib has a dual role as a cyclooxygenase-2 inhibitor, a nonsteroidal anti-inflammatory drug (NSAID), and an analgesic. It is a sulfone butenolactone compound. Rofecoxib is used to treat osteoarthritis, rheumatoid arthritis, acute pain in adults, primary dysmenorrhea, and acute migraine attacks with or without aura. Rofecoxib is a solid. This compound belongs to the stilbene class. These are organic compounds containing a 1,2-stilbene moiety. Stilbene compounds (C6-C2-C6) are derived from the common styrene (C6-C3) skeletal unit. Introducing one or more hydroxyl groups onto the benzene ring yields stilbene compounds. Rofecoxib has a half-life of 17 hours and an average oral bioavailability of approximately 93% at recommended therapeutic doses of 125, 25, and 50 mg. Rofecoxib targets proteins including elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, cytochrome P450 3A4, cytochrome P450 2C9, cytochrome P450 2C8, and prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck withdrew rofecoxib from the market due to the potential increase in the risk of heart attack and stroke with long-term high-dose use. Rofecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that selectively inhibits cyclooxygenase-2 (Cox-2) and was previously used to treat chronic arthritis and mild to moderate musculoskeletal pain. In 2004, it was withdrawn from the market due to the association of long-term use with an increased risk of cardiovascular events. In addition, rofecoxib has been associated with transient elevations in serum transaminases during treatment and rare drug-induced liver disease. Rofecoxib is a synthetic nonsteroidal derivative of phenylfuranone with anti-inflammatory, antipyretic, and analgesic effects, and may have antitumor activity. Rofecoxib binds to and inhibits cyclooxygenase-2 (COX-2), thereby inhibiting the conversion of arachidonic acid to prostaglandins. The COX-related metabolic pathway may be a key regulator of cell proliferation and angiogenesis. Certain epithelial tumor cell types overexpress pro-angiogenic COX-2. (NCI04)

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Drug Indications
For the treatment of osteoarthritis, rheumatoid arthritis, acute pain and primary dysmenorrhea in adults, and acute attacks of migraine with or without aura.
FDA Label
Mechanism of Action
The anti-inflammatory, analgesic, and antipyretic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be achieved by inhibiting prostaglandin synthesis. Although its exact mechanism of action is not fully understood, these effects appear to be achieved by inhibiting COX-2 isoenzymes at sites of inflammation, thereby reducing the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits cyclooxygenase-2 (COX-2), an enzyme that plays a crucial role in mediating inflammation and pain. Unlike non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), rofecoxib does not inhibit platelet aggregation and has very low or almost no affinity for COX-1. Rofecoxib is an NSAID with anti-inflammatory, analgesic, and antipyretic therapeutic effects. Studies have suggested that rofecoxib reduces the production of prostaglandin precursors by inhibiting the activity of cyclooxygenase-2 (COX-2). At therapeutic concentrations, rofecoxib does not inhibit cyclooxygenase-1 (COX-1) isoenzymes in the human body.

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Therapeutic Use
/September 20, 2004/ Merck announced that, due to an increased risk of cardiovascular events (including heart attack and stroke) in patients taking rofecoxib (Vioxx), the company has voluntarily withdrawn rofecoxib (Vioxx) from the U.S. and global markets for safety reasons. Vioxx is a prescription COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) approved by the FDA in May 1999 for the relief of signs and symptoms of osteoarthritis, the treatment of acute pain in adults, and the relief of dysmenorrhea symptoms. It was later approved for the relief of signs and symptoms of rheumatoid arthritis in adults and children.
Anti-inflammatory drug.
Rofecoxib is indicated for the relief of signs and symptoms of osteoarthritis. /U.S. product label includes/
Rofecoxib is indicated for short-term (5 days) relief of acute pain, especially in cases requiring anti-inflammatory effects, such as after dental or orthopedic surgery. /US product label contains/
Rofecoxib is indicated for short-term (5 days) relief of pain and other symptoms of primary dysmenorrhea. /US product label contains

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Drug Warning
/ Merck announced a voluntary withdrawal of Vioxx (rofecoxib) from the US and global markets due to an increased risk of cardiovascular events (including heart attack and stroke) in patients taking Vioxx, posing a safety concern. Vioxx is a prescription COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) approved by the FDA in May 1999 for the relief of signs and symptoms of osteoarthritis, the treatment of acute pain in adults, and the treatment of menstrual symptoms. It was later approved for the relief of signs and symptoms of rheumatoid arthritis in adults and children.
Currently, whether cyclooxygenase-2 (COX-2) specific inhibitors cause elevated blood pressure, thus requiring treatment in clinical practice, remains controversial. We conducted a retrospective case-control study of 17,844 subjects aged ≥65 years from two US states to assess the risk of new-onset hypertension. We used a multivariate logistic regression model to assess the relative risk of developing new-onset hypertension requiring treatment in patients taking celecoxib or rofecoxib compared to patients taking other COX-2 specific inhibitors, nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), or not taking any NSAIDs. During the study period from 1999 to 2000, a total of 3915 patients were diagnosed with hypertension and started treatment; each case was matched with 4 controls. In all models, celecoxib was not significantly associated with the occurrence of hypertension. Patients taking rofecoxib had a significantly increased relative risk of developing new-onset hypertension compared to patients taking celecoxib (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.2 to 2.1), patients taking nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 1.4; 95% CI 1.1 to 1.9), or patients not taking NSAIDs (OR 1.6; 95% CI 1.3 to 2.0). No significant effect was found in dosage or duration of treatment. In patients with a history of chronic kidney disease, liver disease, or congestive heart failure, the relative risk of developing new-onset hypertension was twice that of patients taking rofecoxib compared to those taking celecoxib (OR 2.1; 95% CI 1.0 to 4.3). In this retrospective case-control study of patients ≥ 65 years of age, rofecoxib use was associated with an increased relative risk of new-onset hypertension. This was not observed in patients taking celecoxib. In a double-blind study, 35 stable subjects (taking low-dose aspirin, with ≥ 2 previous acute coronary events and two screening CRP values > 2.0 mg/L) were randomized to either the COX-2 inhibitor rofecoxib (25 mg) or placebo, taken daily for 6 months. Serum CRP, interleukin-6 (IL-6), P-selectin, matrix metalloproteinase-9 (MMP-9), and brachial artery endothelial function were assessed. In the placebo group, the median baseline CRP was 3.16 mg/L (25% and 75% quartiles were 1.90 and 5.78 mg/L, respectively), and at 6 months it was 4.22 mg/L (25% and 75% quartiles were 2.04 and 6.25 mg/L, respectively). In the rofecoxib group, the baseline CRP level was 3.45 mg/L (25% and 75% quartiles were 2.08 and 5.78 mg/L, respectively), and at 6 months it was 1.41 mg/L (25% and 75% quartiles were 1.17 and 4.81 mg/L, respectively) (P=0.03). Compared with placebo, rofecoxib also reduced IL-6 levels at 6 months (P=0.0002). After 3 months of treatment, significant discontinuation effects were observed in CRP and IL-6 levels in the rofecoxib group (P=0.005 and P=0.009, respectively). Rofecoxib had no significant effect on P-selectin, MMP-9, or brachial artery vascular reactivity. Long-term COX-2 inhibition reduced CRP and IL-6 levels without affecting P-selectin and MMP-9, and had no adverse effect on endothelial function in stable patients with a history of recurrent acute coronary events and elevated CRP. These results further support the rationale for evaluating the clinical benefit of COX-2 inhibitors in patients with ischemic heart disease. A 73-year-old woman with rheumatoid arthritis was given rofecoxib 25 mg/day in addition to other medications (her condition was stable). Six months after starting rofecoxib, linear plaques appeared in the infraorbital and temporal regions of both eyes. Several pruritic purplish-red papules also appeared on the right wrist and left dorsum of the foot. Pigmentation also appeared on the right buccal mucosa. Because the rash was localized and the patient was initially unwilling to undergo a skin biopsy, rofecoxib was continued and topical steroids were started. One month later, the patient returned to the dermatology clinic with significantly improved skin response. The skin biopsy performed during this visit was consistent with a diagnosis of LDE. The following day, her rheumatologist decided to discontinue the causative drug, rofecoxib. Two months later, all skin lesions had completely resolved. Rofecoxib was not used again. LDE is a rare skin reaction that can be associated with multiple medications. Rofecoxib is a cyclooxygenase-2 inhibitor, and there have been no previous reports of LDE. An objective causality assessment suggests that rofecoxib may have been the cause of the skin reaction.
For more complete data on rofecoxib (31 total), please visit the HSDB records page.

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Pharmacodynamics
Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor, belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs). Unlike celecoxib, rofecoxib does not contain a sulfonamide chain and its metabolism does not require the CYP450 enzyme. Like other NSAIDs, rofecoxib has anti-inflammatory, analgesic, and antipyretic effects. NSAIDs appear to inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX), which is responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. At least two isoenzymes, COX-1 and COX-2, have been identified. Although the exact mechanism is not fully elucidated, nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory, analgesic, and antipyretic effects primarily by inhibiting COX-2. Inhibition of COX-1 is the main reason for their adverse effects on the gastrointestinal mucosa. Because rofecoxib is selective for COX-2, it may be associated with a reduced risk of certain adverse events, but more data are needed to fully evaluate the drug. Rofecoxib is a selective COX-2 inhibitor used to treat pain and inflammation caused by diseases such as osteoarthritis and rheumatoid arthritis, with fewer gastrointestinal side effects compared to non-selective NSAIDs [1].
- The inhibitory effect of rofecoxib on retinal neovascularization suggests that it has potential therapeutic value in neovascular eye diseases such as diabetic retinopathy and age-related macular degeneration[2].
- The synergistic effect of rofecoxib and gefitinib in mesothelioma cells supports the exploration of combining COX-2 inhibitors with EGFR inhibitors for the treatment of mesothelioma, especially for patients with high COX-2 expression[3].

C17H14O4S

314.36

314.061

162011-90-7

Rofecoxib-d5;544684-93-7

5090

Light yellow to green solid powder

1.3±0.1 g/cm3

577.6±50.0 °C at 760 mmHg

207°C

303.1±30.1 °C

0.0±1.6 mmHg at 25°C

1.619

1.34

0

4

3

22

556

0

RZJQGNCSTQAWON-UHFFFAOYSA-N

InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3

3-(4-methylsulfonylphenyl)-4-phenyl-2H-furan-5-one

MK-0966; MK0966; MK0966; MK966; MK966; MK 966; MK 0966; Trade name: Vioxx; Ceoxx; Ceeoxx.

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 (7.95 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 2: 30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL

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