Ibuprofen

206.28100

206.28

239-784-6

757073|256857

DTXSID5020732

Colorless, crystalline stable solid

C01EB16|M01AE01|C - Cardiovascular system|G - Genito urinary system and sex hormones|M - Musculo-skeletal system|R - Respiratory system

2924299090

37.30000

3.5

Solid

0.9181 g/cm³ @ Temp: 30 °C

75-77 °C

141-142 °C @ Press: 100 Torr

216.7ºC

1.5500 (estimate)

H2O: insoluble

Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

0.000139mmHg at 25°C

LD50 in male mice, rats (mg/kg): 495, 626 i.p.; 1255, 1050 orally (Orzalesi)

Characteristic odor

5.3None

5.3|pKa= 5.2|pKa = 4.91

144 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

III

6.1(b)

UN 2811

3

R22; R51/53; R63

S36/37-S61

MU6640000

Xn

Stable. Combustible. Incompatible with strong oxidizing agents.

P301 + P312 + P330

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Aycock DG; Ibuprofen: A Monograph; Am Pharm NS31 (1): 46-9 (1991). Nonprescription ibuprofen is useful for managing minor aches and pains, reducing fever, and relieving symptoms of dysmenorrhea. For these indications, ibuprofen's effectiveness has been judged to be equal or superior to other available nonprescription analgesics. Ibuprofen is not recommended for self treatment in children less than 12 years old.|Smolinske SC et al; Toxic Effects of Nonsteroidal Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-response Relationships; Drug Saf 5 (4): 252-74 (1990).|Maniglia R et al; Non-steroidal Anti-inflammatory Nephrotoxicity; Ann Clin Lab Sci 18 (3): 240-52 (1988). Non-steroidal anti-inflammatory drugs have a wide range of use in clinical practice because of their analgesic and anti-inflammatory properties. However, their potential nephrotoxicity has been noted. The case histories were studied, retrospectively, in 13 patients who were taking non-steroidal anti-inflammatory drugs as follows: four on fenoprofen (Nalfon), three on naproxen (Naprosyn), two on ibuprofen (Motrin), two on sulindac (Clinoril), one on tolmetin (Tolectin), and one on indomethacin (Indocin) and who exhibited abnormal urinalysis or a deterioration in renal function. Nine of the patients underwent renal biopsies, and eight of these biopsies were positive for interstitial nephritis. In addition to the presentation of additional cases of non-steroidal anti-inflammatory drug nephrotoxicity, a brief review of the current theories of the nephrotoxic mechanism is presented.|Linden CH, Townsend PL; Metabolic Acidosis After Acute Ibuprofen Overdosage; J Pediatr 111 (6 Pt 1): 922-5 (1987). Despite the widespread use of non-steroidal anti-inflammatory drugs, the current number of reported cases of poisoning is small. However, with the introduction of 'over-the-counter' preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected.|Busson M; Update on Ibuprofen: Review Article; J Int Med Res 14 (2): 53-62 (1986). Non-steroidal anti-inflammatory drugs have become the principal mode of therapy for rheumatic diseases and their use has continued to increase despite concern expressed recently regarding potential hazards.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P304+P340, P305+P351+P338, P308+P313, P312, P330, P337+P313, P403+P233, P405, and P501|Aggregated GHS information provided by 551 companies from 44 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P263, P264, P270, P273, P281, P301+P312, P308+P313, P309+P311, P314, P330, P391, P405, and P501

Ibuprofen was qualitatively identified in municipal wastewater at the Iona Island (British Columbia, Canada) treatment plant(1). The compound has been measured in an effluent sedimentation tank, River Rhine water, and unspecified river water samples at up to 12 ug/l, <5 to 41 ng/l, and 17 to 139 ng/l, respectively(2). Ibuprofen was present in the effluent of wastewater treatment plants in Switzerland at concentrations of up to 3 ug/l(3). The compound, which was detected in effluent from a municipal sewage treatment plant near Frankfurt/Main, Germany, decreased by 90% from a daily influent load of 250 g/day(4). Ibuprofen was not detected in 16 effluent samples from treatment plants in Germany, detection limit of 0.010 ug/l(4).

The symptoms of overdose are presented in individuals that consumed more than 99 mg/kg. Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients). The reported LD50 of ibuprofen is of 636 mg/kg in rat, 740 mg/kg in mouse and 495 mg/kg in guinea pig.[MSDS]

Rates of serum aminotransferase elevations during low dose, chronic ibuprofen therapy are comparable to those that occur with placebo controls (0.4%). However, higher rates of ALT elevations occur with high, full doses of 2,400 to 3,200 mg daily (up to 16%). Generally, ALT elevations are mild and rarely above 100 U/L. Ibuprofen overdose (>5-10 grams) is characterized by onset of agitation and stupor 3 to 6 hours after ingestion, followed by coma, respiratory depression and lactic acidosis which can be fatal. Most cases of ibuprofen overdose, however, have not been accompanied by prominent liver injury or jaundice.

IN RABBITS AND IN HEALTHY HUMANS, IBUPROFEN ADMINISTERED BEFORE TOLBUTAMIDE ANTAGONIZED TOLBUTAMIDE HYPOGLYCEMIA.|WHEN SULFAMETHIZOLE WAS COADMINISTERED TO DOGS WITH IBUPROFEN, BETA-ELIMINATION HALF-LIFE FOR SULFAMETHIZOLE WAS INCREASED APPROXIMATELY 10 TIMES COMPARED TO THE CONTROL VALUE. RESULTS SUGGEST THAT THE INCREASED TERMINAL HALF-LIFE OF SULFAMETHIZOLE CAUSED BY IBUPROFEN IS MAINLY A RESULT OF COMPETITIVE INTERACTIONS BETWEEN THEM AT THE RENAL SECRETORY LEVEL.|In several short-term, controlled studies, ibuprofen did not have a substantial effect on the prothrombin time of patients receiving oral anticoagulants; however, because ibuprofen may cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time and because bleeding has occurred when ibuprofen and coumarin derivative anticoagulants were administered concomitantly, the drug should be used with caution and the patient carefully observed if the drug is used concomitantly with any anticoagulant /such as/ warfarin or /the thrombolytic agent streptokinase.|To study a potential interaction between digoxin and two non-steroid anti-inflammatory drugs, indomethacin (50 mg three times daily) and ibuprofen (600 mg three times daily) were given for 10 days to 10 and 8 patients, respectively, on chronic digoxin treatment. Serum digoxin measured by fluorescence polarisation immunoassay increased significantly (p < 0.05) during treatment with indomethacin from pre-treatment values of 0.73 + or - 0.34 nmol/l (mean + or - standard deviation) to a mean value of 1.02 + or - 0.43 nmol/l, while administration of ibuprofen did not change the steady state serum concentration of digoxin. The result demonstrates that some non-steroidal anti-inflammatory drugs such as indomethacin increase serum digoxin to levels high in the therapeutic range. This should be taken into consideration when co-administering other drugs known to increase the serum concentration of digoxin such as several antiarrhythmics.|For more Interactions (Complete) data for IBUPROFEN (17 total), please visit the HSDB record page.

LD50 Rat oral 636 mg/kg|LD50 Rat ip 626 mg/kg|LD50 Rat sc 740 mg/kg|LD50 Rat rectal 530 mg/kg|For more Non-Human Toxicity Values (Complete) data for IBUPROFEN (8 total), please visit the HSDB record page.

Ibuprofen dosage is more than 99% bound to plasma proteins and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml.

Ibuprofen's production and use as an anti-inflammatory, analgesic, and antipyretic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a log Kow of 3.97(2) and a regression-derived equation(3), indicates that ibuprofen is expected to have slight mobility in soil(SRC). Volatilization of ibuprofen from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 4.7X10-5 mm Hg(4), and water solubility, 21 mg/l(5). Ibuprofen is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). A half-life of 20 days using water samples from Lake Greifensee, Switzerland incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(6) indicates that biodegradation in soil may be an important environmental fate process(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,400(SRC), determined from a log Kow of 3.97(2) and a regression-derived equation(3), indicates that ibuprofen is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.5X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 4.7X10-5 mm Hg(4), and water solubility, 21 mg/l(5). The pKa of ibuprofen is 4.9(6), indicating that this compound will primarily exist in the dissociated form in the environment and anions generally do not adsorb to organic carbon and clay more strongly than their neutral counterparts(7). Hydrolysis is not expected be an important environmental fate process as carboxylic acids are generally resistant to hydrolysis(3). According to a classification scheme(8), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A half-life of 20 days using water samples from lake Greifensee, Switzerland incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(10) indicates that biodegradation in water may be an important environmental fate process(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ibuprofen, which has a vapor pressure of 4.7X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase ibuprofen is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 32 hrs(SRC), calculated from its rate constant of 1.16X10-11 cu cm/molecule-sec at 25 °C(3). Particulate-phase ibuprofen may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of ibuprofen with photochemically-produced hydroxyl radicals has been estimated as 1.2X10-11 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 32 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Carboxylic acids are generally resistant to hydrolysis(2). Therefore, hydrolysis is not expected to be an important removal process of ibuprofen from water systems(SRC). Ibuprofen is not expected to directly photolyze due to the lack of absorption in the environmental UV spectrum (>290 nm).

An estimated BCF of 3 was calculated for ibuprofen(SRC), using a log Kow of 3.97(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of ibuprofen is estimated as 3,400(SRC), using a log Kow of 3.97(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that ibuprofen is expected to have slight mobility in soil. The pKa of ibuprofen is 4.91(4), indicating that this compound will primarily exist in the dissociated form in the environment and anions generally do not adsorb to organic carbon and clay more strongly than their neutral counterparts(5).

The Henry's Law constant for ibuprofen is estimated as 1.5X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 4.7X10-5 mm Hg(1), and water solubility, 21 mg/l(2). This Henry's Law constant indicates that ibuprofen is expected to be essentially nonvolatile from water surfaces(3). Ibuprofen is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

GROUNDWATER: Ibuprofen is one of the drugs earmarked by the US Geological Survey for inclusion in a survey of 80 groundwater sources(1).|SURFACE WATER: Ibuprofen was present in surface water samples from rivers and lakes in Switzerland and in samples from the North Sea at concentrations up to 8 ng/l(1). Specific concentrations were as follows (Aug, 1996 - Nov, 1997): Greifensee outlet, 2.0-7.8 ng/l; Aabach tributary, not detected to 2.4 ng/l, Pfaffikersee, 4.0 ng/l, Zurichsee, 3.3-5.0 ng/l, Baldeggersee, 1.5-3.2 ng/l(1). It was detected in samples from the Sempachersee and the North Sea, but not in samples from various mountain lakes in Switzerland(1). Ibuprofen was not detected in 26 samples from 20 rivers and streams in Germany, detection limit of 0.010 ug/l(2).|SURFACE WATER: In a survey conducted by the United States geological Survey, ibuprofen was detected at a maximum concentration of 1.0 ug/l (0.20 ug/l median concn, 0.018 ug/l reporting level) at a 9.5% frequency in 84 submitted water samples from a network of 139 US stream sampling sites across 30 states during 1999-2000(1).

Not excreted in breast milk. /from Table II/

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,249 workers (1,246 of these are female) are potentially exposed to ibuprofen in the US(1). Occupational exposure to ibuprofen may occur through inhalation and dermal contact with this compound at workplaces where ibuprofen is produced or used(SRC). Monitoring data indicate that the general population may be exposed to ibuprofen via intentional oral ingestion for medicinal purposes, ingestion of drinking water, and dermal contact with this compound and other consumer products containing ibuprofen(SRC).

Ibuprofen is the most commonly used and prescribed NSAID. It is very common over the counter medication widely used as an analgesic, anti-inflammatory and antipyretic. The use of ibuprofen and its enantiomer [DB09213] in a racemic mix is common for the management of mild to moderate pain related to dysmenorrhea, headache, migraine, postoperative dental pain, spondylitis, osteoarthritis, rheumatoid arthritis, and soft tissue disorder. Due to its activity against prostaglandin and thromboxane synthesis, ibuprofen has been attributed to alteration of platelet function and prolongation of gestation and labor. As ibuprofen is a widely used medication, the main therapeutic indications are: * Patent Ductus Arteriosus - it is a neonatal condition wherein the ductus arteriosus (blood vessel that connects the main pulmonary artery to the proximal descending aorta) fails to close after birth causing severe risk of heart failure. The prostaglandin inhibition of ibuprofen has been studied for the treatment of this condition as it is known that prostaglandin E2 is responsible for keeping the ductus arteriosus open. * Rheumatoid- and osteo-arthritis - ibuprofen is very commonly used in the symptomatic treatment of inflammatory, musculoskeletal and rheumatic disorders. * Cystic fibrosis - the use of high dosages of ibuprofen has been proven to decrease inflammation and decreasing polymorphonuclear cell influx in the lungs. * Orthostatic hypotension - ibuprofen can induce sodium retention and antagonize the effect of diuretics which has been reported to be beneficial for patients with severe orthostatic hypotension. * Dental pain - ibuprofen is used to manage acute and chronic orofacial pain. * Minor pain - ibuprofen is widely used to reduce minor aches and pains as well as to reduce fever and manage dysmenorrhea. It is very commonly used for the relief of acute indications such as fever and tension headaches. * Investigational uses - efforts have been put into developing ibuprofen for the prophylaxis of Alzheimer's disease, Parkinson disease, and breast cancer.|FDA Label|Treatment of a haemodynamically significant patent ductus arteriosus in preterm newborn infants less than 34 weeks of gestational age.,|Treatment of pain|Treatment of febrile disorders, Treatment of pain|Treatment of nasal congestion and inflammations, Treatment of febrile disorders, Treatment of pain|Acute pain|Chronic pain due to arthropathies|Fever, Pain|Mild to moderate pain with sleeplessness

Ibuprofen is a commonly used nonsteroidal antiinflammatory (NSAID) drug which is available both by prescription and over-the-counter. Ibuprofen is considered to be among the safest NSAIDs and is generally well tolerated but can, nevertheless, rarely cause clinically apparent and serious acute liver injury.

Nonsteroidal Antiinflammatory Drugs

Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors|Ibuprofen ... /is/ indicated for reduction of fever. /Included in US product labeling/|Ibuprofen ... /is/ used for relief of the pain and inflammation of acute gouty arthritis and acute calcium pyrophosphate deposition disease (pseudogout; chondrocalcinosis articularis; synovitis, crystal-induced). Only immediate-release dosage forms are recommended for relief of acute attacks because of their more rapid onset of action relative to delayed-release or extended-release dosage forms. /NOT included in US product labeling/|Ibuprofen ... /is/ indicated for relief of mild to moderate pain, especially when anti-inflammatory actions may also be desired, e.g., following dental, obstetric, or orthopedic surgery, and for relief of musculoskeletal pain due to soft tissue athletic injuries (strains or sprains). Only immediate-release dosage forms are recommended for relief of acute pain because of their more rapid onset of actin relative to delayed-release or extended-release dosage forms. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for IBUPROFEN (28 total), please visit the HSDB record page.

Ibuprofen should be used with caution in patients with peptic ulcer disease, GI perforation or bleeding, bleeding abnormalities (especially in patients who may be adversely affected by prolongation of bleeding time), impaired renal function, hypertension, or compromised cardiac function.|CAUTION IN THE USE OF IBUPROFEN IN SYSTEMIC LUPUS ERYTHEMATOSUS IS ADVISED, PARTICULARLY IF THERE IS HISTORY OF SALICYLATE INTOLERANCE.|Ibuprofen is not recommended for use by pregnant women, or by those who are breast-feeding their infants.|IBUPROFEN ELEVATES BILIRUBIN, ALKALINE PHOSPHATASE, ASPARTATE AMINOTRANSFERASE (SGOT), AND ALANINE AMINOTRANSFERASE (SGPT) ABOVE THE NORMAL RANGE, AND CAUSES ISOLATED CASES OF JAUNDICE. /FROM TABLE/|For more Drug Warnings (Complete) data for IBUPROFEN (14 total), please visit the HSDB record page.

A study of the pharmacokinetic variables of a single oral ibuprofen dose of 600 mg to 15 patients (aged 65-80 yr) with rheumatic diseases to determine tolerance under the aspect of cumulating effects in the serum level concentration is described. Results show no clinically significant deviation of the values compared with published data in younger patients.

Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials. The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region. The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system. In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS. (See all compounds classified as Analgesics, Non-Narcotic.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. (See all compounds classified as Cyclooxygenase Inhibitors.)

It is very well absorbed orally and the peak serum concentration can be attained in 1 to 2 hours after extravascular administration. When ibuprofen is administered immediately after a meal there is a slight reduction in the absorption rate but there is no change in the extent of the absorption. When orally administered, the absorption of ibuprofen in adults is very rapidly done in the upper GI tract. The average Cmax, Tmax and AUC ranges around 20 mcg/ml, 2 h and 70 mcg.h/ml. These parameters can vary depending on the enantiomer form, route, and dose of administration.|Ibuprofen is rapidly metabolized and eliminated in the urine thus, this via accounts for more than 90% of the administered dose. It is completely eliminated in 24 hours after the last dose and almost all the administered dose goes through metabolism, representing about 99% of the eliminated dose. The biliary excretion of unchanged drug and active phase II metabolites represents 1% of the administered dose. In summary, ibuprofen is excreted as metabolites or their conjugates. The elimination of ibuprofen is not impaired by old age or the presence of renal impairment.|The apparent volume of distribution of ibuprofen is of 0.1 L/kg.|The clearance rate ranges between 3-13 L/h depending on the route of administration, enantiomer type and dosage.|Ibuprofen is rapidly absorbed after oral admin, & peak concns in plasma are observed after 15-30 min. The half-life in plasma is about 2 hr. Ibuprofen is extensively (99%) bound to plasma proteins, but the drug occupies only a fraction of the total drug-binding sites at usual concns. Ibuprofen passes slowly into the synovial spaces & may remain there in higher concn as the concns in plasma decline. In experimental animals, ibuprofen & its metabolites pass easily across the placenta. The excretion of ibuprofen is rapid & complete. More than 90% of an ingested dose is excreted in the urine as metabolites or their conjugates.|ENTERO-HEPATIC CIRCULATION OF (14)C-IBUPROFEN & ITS METABOLITES MAY HAVE OCCURRED IN DOGS RECEIVING REPEATED ORAL DOSES ... SINCE LEVELS IN BILE ... WERE 40-FOLD THOSE IN PLASMA.|AFTER ORAL DOSES OF 400 MG IBUPROFEN, SERIAL BLOOD SAMPLES WERE TAKEN (5 MALE VOLUNTEERS, 4 ARTHRITIC PATIENT). EVIDENCE SHOWED 2 COMPARTMENT MODEL: NO EVIDENCE SHOWN OF DRUG ACCUM IN PERIPHERAL COMPARTMENT.|The enantiomeric composition of ibuprofen in plasma was investigated following oral administration of 200 mg of the racemic drug in a conventional tablet or 300 mg in a novel controlled release pellet formulation to 4 healthy volunteers, aged 24 to 37 yr, in a randomized, crossover study. The plasma concentration time profiles suggest that drug release from the controlled release preparation was suitably modified and that the fluctuation between the peaks and troughs observed following a conventional tablet formulation were reduced. The plasma concentrations of (+)-ibuprofen (S-ibuprofen) were greater than those of (-)-ibuprofen (R-ibuprofen) following either formulation, and the enantiomeric plasma ratio (S/R) was reduced, both in magnitude and variability, following the controlled release preparation. The proportion of the total area under the plasma concentration time curves, due to (S)-ibuprofen, were slightly reduced following the controlled release formulation compared to the tablet formulation. The importance of a consideration of stereochemistry in bioequivalence studies of chiral drugs is discussed.|For more Absorption, Distribution and Excretion (Complete) data for IBUPROFEN (11 total), please visit the HSDB record page.

Ibuprofen is rapidly metabolized and biotransformed in the liver to the formation of major metabolites which are the hydroxylated and carboxylated derivatives. As soon as it is absorbed, the R-enantiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer _in vivo_ by the activity of alpha-methylacyl-CoA racemase. Ibuprofen metabolism can be divided in phase I which is represented by the hydroxylation of the isobutyl chains for the formation of 2 or 3-hydroxy derivatives followed by oxidation to 2-carboxy-ibuprofen and p-carboxy-2-propionate. These oxidative reactions are performed by the activity of the cytochrome P450 isoforms CYP 2C9, CYP 2C19 and CYP 2C8. Therefore, these enzymes participate in the oxidation of the alkyl side chain to hydroxyl and carboxyl derivatives. From this enzymes, the major catalyst in the formation of oxidative metabolites is the isoform CYP 2C9. The metabolic phase I is followed by a phase II in which the oxidative metabolites may be conjugated to glucuronide prior to excretion. This activity forms phenolic and acyl glucuronides.|TWO MAJOR METABOLIC PATHWAYS IN MAN & IN ANIMALS PROCEED BY OXIDATIVE ATTACK OF ISOBUTYL SIDE CHAIN; THEY ARE HYDROXYLATION OF THE TERTIARY CARBON TO YIELD A STABLE TERTIARY ALCOHOL, & OXIDATION OF 1 OF THE 2 GEMINAL METHYL GROUPS TO YIELD THE ACID.|IBUPROFEN GIVES 2-(4-(2-CARBOXYPROPYL)PHENYL)PROPIONIC ACID & 2-(4-(2-HYDROXY-2-METHYLPROPYL)PHENYL)PROPIONIC ACID IN MAN. /FROM TABLE/|The pharmacokinetics of oral ibuprofen following a dose of 0.8 g given 3 times a day for 14 days were studied in 7 functionally anephric patients (aged 34-66 yr) undergoing hemodialysis. No accumulation of ibuprofen plasma concns & an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly with mean plasma levels of 249 mcg/ml for the carboxy derivatives & 57 mcg/ml for the hydroxy derivatives of ibuprofen. However, both were detected in the dialysate. Dialysis clearance calculated by arterial & venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.

The serum half-life of ibuprofen is 1.2-2 hours. In patients with a compromised liver function, the half-life can be prolonged to 3.1-3.4 hours.|... After oral admin ... the half-life in plasma is about 2 hr.

The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.|IBUPROFEN AT 25 MG/KG IV INCREASED THE PRIMARY AND TOTAL HEMOSTATIC PLUG FORMATION TIME IN RABBIT EAR CHAMBERS WITH LASER-INDUCED INJURY. THE SAME DOSE INCREASED THE NUMBER OF CUMULATIVE EMBOLI OVER A 10 MINUTE PERIOD AFTER A LASER INJURY TO ARTERIOLES. IN DOGS, DOSES OF 10, 25, AND 50 MG/KG DID NOT ENHANCE THE RELEASE OF (125)I-LABELED FIBRIN DEGRADATION PRODUCTS FROM THE THROMBI AFTER INCUBATION IN PLASMIN, BUT THE LARGEST DOSE SIGNIFICANTLY DECREASED THE THROMBUS WEIGHT 90 AND 180 MINUTES AFTER DRUG ADMINISTRATION. THUS, IBUPROFEN HAD AN INHIBITORY EFFECT ON PLATELET FUNCTION IN VIVO AND IN LARGE DOSES DIMINISHED THE THROMBUS WEIGHT.|L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response.|We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open field behavior (p < 0.05), restoring values similar to Tg- mice. Reduced caspase activation per plaque provided further evidence for a neuroprotective action of ibuprofen.The impact of a shorter 3 month duration ibuprofen trial, beginning at a later age (from 14 to 17 months), was also investigated. Repeated measures ANOVA of Abeta levels (soluble and insoluble) demonstrated a significant ibuprofen treatment effect (p < 0.05). Post-hoc analysis showed that ibuprofen-dependent reductions of both soluble Abeta and Abeta42 were most marked in entorhinal cortex (p < 0.05). Although interleukin-1beta and insoluble Abeta were more effectively reduced with longer treatment, the magnitude of the effect on soluble Abeta was not dependent on treatment duration.|Trying to decrease the production of Amyloid beta (Abeta) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFalpha with IFNgamma induces the production of Abeta-42 and Abeta-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFalpha and IFNgamma. Ibuprofen treatment decreased the secretion of total Abeta in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Abeta-42 and Abeta-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Abeta by ibuprofen was presumably due to a decreased production of betaAPP, which in contrast to the control proteins M2 pyruvate kinase, beta-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.

When acute overdosage of ibuprofen occurs, the stomach should be emptied by inducing emesis or by lavage, particularly if there is evidence that the drug has been ingested recently (within 1 hour), and standard measures to maintain urine output should be instituted. Since ibuprofen is acidic and is excreted in the urine, alkaline diuresis might be beneficial.

Gastrointestinal side effects are experienced by 5-15% of patients taking ibuprofen; epigastric pain, nausea, heartburn, & sensations of "fullness" in the GI tract are the usual difficulties. However, the incidence of theses side effects is less with ibuprofen than with aspirin or indomethacin. Other side effects of ibuprofen have been reported less frequently. They include thrombocytopenia, skin rashes, headache, dizziness & blurred vision, & in a few cases, toxic amblyopia, fluid retention, & edema.|3 YOUNG WOMEN TAKING IBUPROFEN FOR SYSTEMIC LUPUS ERYTHEMATOSUS DISCONTINUED THERAPY: ON REINSTITUTION OF THERAPY, PROFOUND HYPOTENSION & HEADACHES DEVELOPED WITHIN HR.|FATAL AUTOIMMUNE HEMOLYTIC ANEMIA OCCURRED COINCIDENT WITH ORAL ADMIN OF IBUPROFEN 400 MG 3 TIMES/DAY IN 49-YR OLD MALE.|15/21 BLACK PATIENTS SHOWED THINNING OR LOSS OF HAIR WHILE TAKING IBUPROFEN. NORMAL GROWTH RETURNED UPON DISCONTINUATION MEDICATION. POSSIBLE THAT IBUPROFEN ACTS ON PROTEIN TO CAUSE BRITTLENESS, FRAGILITY WHEN HAIR IS EXPOSED TO STRAIGHTENERS, PROCESSES, PERMANENT WAVE PROCEDURES.|For more Human Toxicity Excerpts (Complete) data for IBUPROFEN (18 total), please visit the HSDB record page.

alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid

(1995) Estimated prescription amounts in Germany was 105 tons per year.

Generic. Tablets 200 (nonprescription), 300, 400, 600, and 800 mg. Advil (Whitehall), Medipren (McNeil), Midol 200 (Glenbrook), Nuprin (Bristol-Myers). Tablets 200 mg (nonprescription). Children's Advil Suspension (Whitehall), Pedia-Profen (McNeil). Suspension 100 mg/5 ml. Motrin (Upjohn). Tablets 200 (Motrin IB, nonprescription), 300, 400 600, and 800 mg. Rufen (Boots). Tablets 400, 600, and 800 mg.

Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)-: ACTIVE|Ibuprofen ... is on the top ten list of pharmaceuticals used in Denmark in 1995

Liquid chromatography detector with ultraviolet absorption at a flow rate of 2 ml/m.|Ethambutol hydrogen chloride and ibuprofen were determined in tablets by reversed-phase HPLC using a mu Bondapak C18 column packed with octadecylsilane bonded to porous silica, MeOH-H2O (70:30) mobile phase, and UV detection at 254 nm. The standard deviation and coefficient of variation were 1.82 and 0.252, respectively for ethambutol and 1.61 and 0.432, respectively for ibuprofen. The direct isocratic method requires no separation of drug from other active ingredients, and does not require any derivatization.|Separations by capillary zone electrophoresis in plain, uncoated fused silica capillaries were compared with those in electroendosmosis-free coated capillaries. For small ions, exemplified by some anti-inflammatory drugs, resolution and analysis times were comparable in the two types of capillaries. The advantage of the coated capillary was that it predictably eluted all neg analytes regardless of electrolyte pH. The uncoated capillary, on the other hand, allowed separation of both pos and neg species in one run, provided that the electroendosmotic flow was sufficiently high to elute all neg charged analytes. Because electrolyte conditions were established that eluted all sample analytes, subsequent analyses were performed in uncoated capillaries. Antibiotics such as sulfonamides, cephalosporins, and penicillins were separated by zone electrophoresis. Optimal separation conditions were established by varying the pH and ionic strength of the electrolyte. For the separation. of structurally similar peptides and barbiturates, micellar electrokinetic capillary chromatography was the method of choice because the structural differences conferred differences in hydrophobicity. The feasibility of using capillary zone electrophoresis in pharmaceutical analysis was shown in the evaluation of over-the-counter pain, cold, and allergy medications. These typically gave relative standard deviations of 1% for retention times and 3% for peak areas.|An HPLC method using an internal surface reversed-phase column Pinkerton packed with glycyl-phenylalanyl-phenylalanine phase on silica for the determination of various drugs /including ibuprofen/ is described. The method allows analysis of biological samples without deproteination. Several mobile phases were used. Data for sample prepn and retention times and capacity factors for 28 drugs are given.|For more Analytic Laboratory Methods (Complete) data for IBUPROFEN (7 total), please visit the HSDB record page.

ELECTRON CAPTURE GAS LIQUID CHROMATOGRAPHY DETERMINATION IN SERUM.|HIGH PERFORMANCE LIQUID CHROMATOGRAPHY DETERMINATION OF IBUPROFEN AND ITS MAJOR METABOLITES IN BIOLOGICAL FLUIDS.|A selective reversed-phase HPLC method for the determination of ibuprofen in different ointment bases. Following a simple dilution step, the drug was seperated from interfering cmpd on an octadecylsilica column protected by a precolumn. A mobile phase of aq tetrahydrofuran buffered by phosphate was used. Detection was monitored at 219 nm. After each 10 injections of lipophilic samples, the columns were washed with tetrahydrofuran and n-hexane. Recoveries of ibuprofen from a new pilot prepn spiked to contain 4, 5, and 6% of the drug were 100.4, 100.3, and 99.7%, resp. The precision at each concn was <0.8%. The analysis of ibuprofen degradation products showed that the method also provides an indication of the stability of the drug.|The use of capillary column gas chromatography for drug screening in forensic toxicology has become increasingly widespread. Screening procedures however are often lengthy and unsuitable for rapid confirmatory or quant applications. To develop a practical scheme for confirmatory/quant analysis, a series of temp profiles to allow the rapid quant detn of a wide range of acid/neutral and basic drugs in extracts from post mortem fluids and tissue were optimized. The appropriate profile is selected based on the retention index on a stamdard crosslinked Me silicone column used to screen extracts. The use of a 5% Ph Me silicone phase allows complementary identification, and allows the separation of some pairs of cmpd with identical retention indexes in the screening procedure.|For more Clinical Laboratory Methods (Complete) data for IBUPROFEN (12 total), please visit the HSDB record page.

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