alpha-Methyl-4-(2-methylpropyl)-benzolessigsäure

Pharmaceuticals

Pharmaceuticals -> Used in Switzerland

Pharmaceutical

Pharmaceuticals -> NSAIDs

log Kow= 3.97

3.97

Readily sol in most org solvents

VERY SOLUBLE IN ALCOHOL

In water, 21 mg/l @ 25 °C

0.021 mg/mL at 25 °C

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Medicines administered to the neonate [c]

75-77.5 ºC

75-77 °C

76 °C

Other Solid

Solid

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P304+P340, P305+P351+P338, P318, P319, P330, P337+P317, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 511 reports by companies from 48 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)-

Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 29-03-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/1270

Ibuprofen: Does not have an individual approval but may be used under an appropriate group standard

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.

Acute Tox. 4 (100%)

Acute toxicity (Oral) - Category 4

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.

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.

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. Rare instances of drug fever arise within 1 to 4 weeks of starting ibuprofen which can be accompanied by serum aminotransferase elevations. If ibuprofen is continued in these situations, more severe liver injury and jaundice may arise. These outcomes may account for a rare case of hepatocellular injury attributed to conventional doses of ibuprofen.

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).

Gastrointestinal bleeding is a well-known adverse effect of ibuprofen usage and can lead to gastritis, ulceration, hemorrhage, or perforation. Inhibition of COX isoform production reduces prostaglandin levels, which are involved in gastroprotective mucus secretion. This effect is more pronounced with non-selective NSAIDs; selective COX-2 inhibitors are associated with a lower incidence of gastrointestinal complications, which is of particular concern in children. Ibuprofen is more commonly used than other NSAIDs due to its favorable safety profile. Using ibuprofen over-the-counter without medical consultation increases the risk of high dosage levels and short-term interval dosing that may precipitate gastrointestinal complications.

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 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).

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.

AEROBIC: Ibuprofen has shown to be inherently biodegradable by sewage treatment(1). However, analysis of activated sludge from the wastewater treatment plant at Gossau, Switzerland indicates that a residence time in excess of 6 hours is required for complete removal of ibuprofen(2). A half-life of 20 days was determined from a study using water samples from lake Greifensee, Switzerland that were incubated at room temperature for 37 days with 200 ng/l racemic ibuprofen(2). Influent concentration of 0.3 ug/l in Brazilian treatment plants showed a removal efficiency of ranging from 22-75%(3).

Drug Induced Liver Injury Rank (DILIrank 2.0)

Ibuprofen

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

M01AE01

M - Musculo-skeletal system

C - Cardiovascular system

R - Respiratory system

G - Genito urinary system and sex hormones

M - Musculo-skeletal system

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.

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.

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.

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.

WK2XYI10QM

IBUPROFEN

Mechanisms of Action [MoA] - Cyclooxygenase Inhibitors

Chemical Structure [CS] - Anti-Inflammatory Agents, Non-Steroidal

Established Pharmacologic Class [EPC] - Nonsteroidal Anti-inflammatory Drug

Ibuprofen is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of ibuprofen is as a Cyclooxygenase Inhibitor.

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.

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.

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.

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.

THERAP CAT: Anti-inflammatory; analgesic; antipyretic

THERAP CAT (VET): Anti-inflammatory

Ingredient in over-the-counter pain relievers

Indicated for both acute and long-term management of rheumatoid arthritis, osteoarthritis, and psoriatic arthritis.

For more Uses (Complete) data for IBUPROFEN (7 total), please visit the HSDB record page.

Prepn: J.S. Nicholson, S.S. Adams, GB971700; eidem US 3385886 (1964, 1968 both to Boots Pure Drug); T. Shiori, N. Kawai, J. Org. Chem. 43, 2936 (1978); J.T. Pinhey, B.A. Rowe, Tetrahedron Letters 21, 965 (1980).

Production: isobutylbenzene + acetyl chloride + triethylaluminum + potassium cyanide (Friedel-Crafts acylation/cyanohydrin formation/hydrogenation/nitrile hydrolysis)

Production: isobutylbenzene + propionyl chloride + methanol (Friedel-Crafts acylation/ketal formation/alpha bromination/rearrangement)

Production: isobutylbenzene + acetyl chloride + carbon monoxide (Friedel-Crafts acylation/carbonyl reduction/carbonylation)

For more Methods of Manufacturing (Complete) data for IBUPROFEN (6 total), please visit the HSDB record page.

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.

Pharmaceutical and Medicine Manufacturing

Benzeneacetic acid, .alpha.-methyl-4-(2-methylpropyl)-: ACTIVE

Ibuprofen ... is on the top ten list of pharmaceuticals used in Denmark in 1995