Absorption, Distribution and Excretion
Absorption is rapid on an empty stomach. Peak plasma concentrations of 50 µg/mL are reached within 2 hours after an oral dose of 600 mg. …Rapid absorption after oral administration; peak plasma concentrations occur within 90 minutes. Co-administration with food reduces absorption and bioavailability, but co-administration with antacids does not affect absorption and bioavailability. Fenolofen is well absorbed from the gastrointestinal tract in sodium or calcium form and rapidly cleared by the kidneys. At commonly used doses, fenolofen is well absorbed (over 80%), rapidly reaching steady-state plasma concentrations, and is highly bound to proteins (95-99%). Biotransformation occurs in the liver, and metabolites are excreted in the urine. ...T/2...2.5-3 hours... Following absorption, fenolofen is metabolized and almost completely excreted in the urine as conjugates. ...Highly bound to plasma proteins and may displace other protein-bound drugs from their binding sites, leading to drug interactions.
Plasma and urinary pharmacokinetics of fenprofen after oral and intravenous administration.
Metabolism/Metabolites
Approximately 90% of a single oral dose is excreted within 24 hours as fenprofen glucuronide and 4'-hydroxyfenprofen glucuronide, which are the major urinary metabolites of fenprofen.
...Fenprofen...produces two urinary glucurons in the human body. One compound...constituting approximately half the dose, is an acyl glucuronide...The other compound...constituting approximately half the dose, is a fenprofen phenol derivative glucuronide...an acyl glucuronide with a free phenolic group.
...Fenprofen...is found to produce very small amounts of acid-labeled conjugates, neither glycine nor glutamine conjugates...
Biological half-life
The plasma half-life is approximately 3 hours.
...Rapidly absorbed after oral administration; peak plasma concentrations occur within 90 minutes. The plasma half-life of this drug is approximately 160 minutes and appears to be dose-independent. Taking it with food reduces its absorption and bioavailability, but it is unaffected by concurrent use with antacids. The half-life is 2.5–3 hours.

Hepatotoxicity
Prospective studies have shown that up to 15% of patients taking fenprofen experience at least transient elevations in serum transaminases. These elevations are usually transient, mild, and asymptomatic, and may resolve spontaneously with continued use. Significant transaminase elevations (more than 3-fold increase) are seen on a probability score of D (likely a rare cause of clinically significant liver injury). Use during Pregnancy and Lactation
◉ Overview of Use During Lactation
Some reviewers consider fenprofen acceptable during lactation. Due to limited published experience regarding fenprofen use during lactation, alternative medications may be preferred, especially when breastfeeding newborns or premature infants.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding
The binding rate to albumin is 99%.

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Interactions
When fenprofen is added to the treatment regimen of rheumatoid arthritis patients receiving corticosteroids or gold preparations, there is evidence that it can reduce the dose of steroids, and it is more effective when used in combination with gold preparations.
Food slows absorption…&Combined with antacids, it can reduce peak plasma concentration (approximately 30%) and total absorption (approximately 20%).
/Plasma Proteins/Fenprofen can inhibit its binding when used in combination with indomethacin and phenylbutazone. Aspirin can reduce the plasma half-life of fenprofen.
Fenprofen and propoxyphene have an additive effect when used together.

[1]. A universal methodology for reliable predicting the non-steroidal anti-inflammatory drug solubility in supercritical carbon dioxide. Sci Rep. 2022 Jan 20;12(1):1043.

[2]. Fenoprofen-An Old Drug Rediscovered as a Biased Allosteric Enhancer for Melanocortin Receptors. ACS Chem Neurosci. 2019 Mar 20;10(3):1066-1074.

Fenolofen is a monocarboxylic acid, a derivative of propionic acid, in which a hydrogen atom at the 2-position is replaced by a 3-phenoxyphenyl group. It is a nonsteroidal anti-inflammatory drug (NSAID), and its calcium salt dihydrate is used to treat mild to moderate pain, as well as to relieve pain and inflammation caused by conditions such as arthritis. Its pharmacological action is similar to aspirin, but with less gastrointestinal bleeding. It has multiple functions, including NSAID, cyclooxygenase 2 inhibitor, cyclooxygenase 1 inhibitor, antipyretic, non-narcotic analgesic, and drug allergen. It is the conjugate acid of fenolofen (1-). Fenolofen is an anti-inflammatory, analgesic, and antipyretic drug that is highly bound to plasma proteins. Its pharmacological action is similar to aspirin, but with less gastrointestinal bleeding. Fenolofen is a nonsteroidal anti-inflammatory drug. The mechanism of action of fenolofen is as a cyclooxygenase inhibitor. Fenolofen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat acute pain and chronic arthritis. The incidence of elevated serum enzymes during fenprofen treatment is low, and clinically significant acute liver injury is extremely rare. Fenprofen is a propionic acid derivative with analgesic, nonsteroidal anti-inflammatory, and antirheumatic effects. Fenprofen inhibits two isoenzymes of cyclooxygenase, thereby inhibiting prostaglandin synthesis and blocking the conversion of arachidonic acid to prostaglandins. Furthermore, fenprofen can activate peroxisome proliferator-activated receptors (PPARs) -α and -γ, potentially downregulating leukotriene B4 production. Fenprofen is a propionic acid derivative used as a nonsteroidal anti-inflammatory drug. See also: Fenprofen calcium (salt form); Fenprofen sodium (salt form). Indications: For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis. Also used to relieve mild to moderate pain.
FDA Label
Mechanism of Action
The exact mechanism of action of fenprofen is unclear, but it is believed to be related to the inhibition of prostaglandin synthase. Studies have shown that fenprofen can inhibit prostaglandin synthase isolated from bovine seminal vesicles.
Similar to aspirin, fenprofen can also inhibit prostaglandin synthase, but the relationship between this effect and clinical efficacy is unclear.
Therapeutic Use
Cyclooxygenase inhibitor; nonsteroidal anti-inflammatory drug
…Fenprofen may be tried in patients who cannot tolerate aspirin due to gastrointestinal discomfort. …It has anti-inflammatory, analgesic, and antipyretic effects. …It appears to be effective in treating rheumatoid arthritis…comparable to…aspirin, and…with fewer gastrointestinal reactions and less gastrointestinal bleeding…
…Fenprofen…has been shown to be effective in treating rheumatoid arthritis, manifested by reduction of pain, joint stiffness, swelling, and tenderness. In patients with rheumatoid arthritis, the efficacy of 2.4 g of fenprofen daily is roughly equivalent to that of 3.9 g of aspirin. When fenprofen is added to the treatment regimen of rheumatoid arthritis patients receiving corticosteroids or gold preparations, there is evidence that it can reduce the steroid dose and is more effective when used in combination with gold preparations. For more complete data on the therapeutic uses of fenprofen (7 types), please visit the HSDB record page.

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Drug Warnings
…Clinical experience with newer drugs, including fenprofen, is insufficient to determine their relative efficacy and ultimate role in the treatment of rheumatic diseases. .../fenprofen/ should not be used in patients with bleeding disorders and should be used with caution in patients receiving anticoagulation therapy. .../fenprofen/ is highly bound to plasma proteins and may displace other protein-bound drugs from their binding sites, resulting in drug interactions.

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Pharmacodynamics
Fenolofen is a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic effects. Fenolofen inhibits prostaglandin synthesis by reducing the enzymes required for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory effects of fenolofen have been demonstrated through pain relief, improved grip strength, reduced joint swelling, shortened duration of morning stiffness, and reduced disease activity (co-assessed by investigators and patients). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenolofen have been demonstrated through reduced tenderness, decreased nocturnal pain, joint stiffness, swelling, and reduced overall disease activity (co-assessed by patients and investigators). These effects are also reflected in the relief of pain during activity and rest and increased range of motion of affected joints. Clinical studies in patients with rheumatoid arthritis and osteoarthritis have shown that fenolofen is comparable to aspirin in controlling the above-mentioned disease activity indicators, but the incidence of mild gastrointestinal reactions (nausea, indigestion) and tinnitus was lower in the fenolofen treatment group than in the aspirin treatment group. It is currently unclear whether fenprofen is less likely to cause peptic ulcers than aspirin. In patients with pain, the analgesic effect of fenprofen can reduce pain intensity, enhance analgesia, improve overall pain scores, and provide sustained analgesia.

C15H14O3

242.2699

242.094

29679-58-1

Fenoprofen Calcium hydrate;71720-56-4;Fenoprofen Calcium;34597-40-5;Fenoprofen-13C6 sodium hydrate

3342

Colorless to light yellow viscous liquid

1.2±0.1 g/cm3

381.3±25.0 °C at 760 mmHg

168-171

141.7±16.7 °C

0.0±0.9 mmHg at 25°C

1.583

3.84

1

3

4

18

271

0

O(C1C([H])=C([H])C([H])=C([H])C=1[H])C1=C([H])C([H])=C([H])C(=C1[H])C([H])(C(=O)O[H])C([H])([H])[H]

RDJGLLICXDHJDY-UHFFFAOYSA-N

InChI=1S/C15H14O3/c1-11(15(16)17)12-6-5-9-14(10-12)18-13-7-3-2-4-8-13/h2-11H,1H3,(H,16,17)

2-(3-phenoxyphenyl)propanoic acid

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)

DMSO : ~100 mg/mL (~412.76 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.32 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 (10.32 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 (10.32 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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 (Please use freshly prepared in vivo formulations for optimal results.)