BIOWAIVER MONOGRAGHS of DEXIBUPROFEN Rehnasalim, R
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IJPCBS 2013, 3(2), Rehnasalim et al. ISSN: 2249-9504 INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES Available online at www.ijpcbs.com Review Article BIOWAIVER MONOGRAGHS OF DEXIBUPROFEN Rehnasalim, R. Sivakumar, Krishnapillai, C. Sajeeth and Haribabu Grace College of Pharmacy, Palakkad, Kerala, India. ABSTRACT Literature data are reviewed on the properties of dexibuprofen related to thebiopharmaceutics classification system (BCS). Dexibuprofen was assessed to be a BCS classII drug.This article summarizes the main pharmacological effects, therapeutical applications, adverse drug reactions drug-drug interactions,pharmacokinetic properties, physicochemical properties and BCS classification of dexibuprofen. Dexibuprofen is propionic acid derivatives.It is the active dextrorotatory enantiomer of ibuprofen. Keywords: Dexibuprofen, Drug -drug interaction, Physicchemical properties. INTRODUCTION ibuprofen. Most ibuprofen formulations A monograph based on literature data is contain a racemic mixture of dexibuprofen presented on dexibuprofen concerning its [(+)-ibuprofen] and (−)-ibuprofen. S(+) properties related to the biopharmaceutics Ibuprofen is over 100‐fold more potent an classification system (BCS).. In brief, it is to inhibitor of cyclooxygenase‐I than Dexibuprofen data available from literature R‐Ibuprofen2. Dexibuprofen shows an sources about dexibuprofen. Dexibuprofen equipotency with half of the racemic is the most commonly used and most ibuprofen dose, and the introduction of frequently prescribed NSAID. It is a non- dexibuprofen (Seractil) permits the selective inhibitor of cyclo-oxygenase-1 prescription of lower doses3. (COX-1) and Cyclooxygenase-2 (COX-2). It has a prominent analgesic and antipyretic role. Its effects are due to the inhibitory actions on cyclo-oxygenases, which are involved in the synthesis of prostaglandins. Prostaglandins have an important role in the production of pain, inflammation and fever. LITERATURE DATA Fig. 1: Structure Of Dexibuprofen General Characteristics Dexibuprofen chemical name is(2S)-2-[4- (2-methylpropyl)phenyl] propanoic acid Clinical Pharmacology of Dexibuprofen (and its structure shown in Figure Dexibuprofen is supplied as tablets with a 1.S+Ibuprofen can form salts with bases potency of 200 to 400 mg4. The usual dose such as basic aminoacids, examples are is 600 to 900 mg three times a day5. It is lysine and arginine. The lysine part almost insoluble in water having pKa of enhances, solubility of the ibuprofen in 4.656.It is well absorbed orally; peak serum water and gastric solution(Dexibuprofen) concentrations are attained in 1 to 2 hours obtained with half the dose racemic after oral administration. It is rapidly bio- ibuprofen formulation1. It is the transformed with a serum half life of 1.8 to active dextrorotatory enantiomer of 424 IJPCBS 2013, 3(2), Rehnasalim et al. ISSN: 2249-9504 3.5 hours. The drug is completely dose of ibuprofen. Greater peak analgesia eliminated in 24 hours after the last dose was also seen with. It is indicated and eliminated through metabolism7,8. The dexibuprofen for the relief of sign and drug is more than 99% protein bound, symptoms of osteoarthritis, rheumatoidal extensively metabolized in the liver and disorders such as osseous rheumatism, little is excreted unchanged9. ankylosing sodalities, juvenile arthritis, Although highly bound to plasma proteins muscular rheumatism and degenerative (90-99%), displacement interactions are joint disease. It is also used for the acute not clinically significant, hence the dose of symptomatic treatment of painful oral anti-cogulants and oral hypoglycemic menstruation, symptomatic treatment needs not be altered11. More than 90% of an muscle pain, head ache and dental ingested dose is excreted in the urine as pain.Dexibuprofen has equal efficacy and metabolites or their conjugates, the major comparable safety andtolerability19 with metabolites are hydroxylated and celecoxib in the treatment of the carboxylated compounds4,10. osteoarthritis18.Dexibuprofen shows Renal impairment also has no effect on the excellent tolerability, safety than other kinetics of the drugs, rapid elimination still NSAIDlike diclofenac sodium, dexibuprofen occur as a consequence of metabolism12.The has stronger pain reducingeffect than administration of ibuprofen tablets either racemic ibuprofen. Maximum Daily Dose of under fasting conditions or immediately 3200mg18(adult) of Ibuprofen racemate is before meals yield quiet similar serum required, but dose required concentrations-time profile. When it is fordexibuprofen lysinate is 2692.5 mg of administered immediately after a meal, S+Ibuprofen lysinateequivalent to 1500mg there is a reduction in the rate of absorption of dexibuprofen 200‐300mg every 4‐6 hrs but no appreciable decrease in the extent of forthe relief of pain. S(+) Ibuprofen is absorption. superior in anti‐inflammatoryaction but equal to reacemic ibuprofen in analgesic Therapeutic Applications action. A low dose ibuprofen is as effective as Dexibuprofen is the single aspirin and paracetamol for the indications pharmacologically effective enantiomer of normally treated with over the counter rac-ibuprofen. Racibuprofen and medications13. It is widely used as an dexibuprofen differ in their physico- analgesic, an anti inflammatory and an chemical properties, in terms of their antipyretic agent14-15. Recemic ibuprofen pharmacological properties and their and S(+) enantiomer are mainly used in the metabolic profiles. Several clinical trials and treatment of mild to moderate pain related post-marketing surveillance studies were to dysmenorrhea, headache, migraine, performed to broaden the findings on postoperative dental pain, management of dexibuprofen. In the last 5 years 4836 spondylitis, osteoarthritis, rheumatoid patients have been exposed to dexibuprofen arthritis and soft tissue disorder16. A in clinical trials and PMS trials. Only in 3.7% number of other actions of NSAIDs can also of patients adverse drug reactions have be attributed to the inhibition of been reported and 3 serious adverse drug prostaglandins (PGs) or thromboxane reactions (0.06%) were observed. In the synthesis, including alteration in platelet dose ratio of 1 : 0.5 (rac-ibuprofen vs. function (PGI2 and Thromboxane), dexibuprofen) at least equivalent efficacy prolongation of gestation and labor (PGE2, was proven in acute mild to severe somatic PGF2A), gastrointestinal mucosal damage and visceral pain models. Dexibuprofen has (PGI2 and PGE2), fluid and electrolyte proven at least comparable efficacy to imbalance (renal PGs), premature closure of diclofenac, naproxen and celecoxib and has ductus arteriosus (PGE2) and bronchial shown a favourable tolerability. The results asthma (PGs)17. The advantages of include suggest that dexibuprofen processed in a greater dexibuprofen clinical efficacy, ease special crystal form is a safe and effective in dose optimization, less variability in treatment for different pain conditions. therapeutic effects, all of these at half the 425 IJPCBS 2013, 3(2), Rehnasalim et al. ISSN: 2249-9504 Indication to 1% with placebo and 12.5% with Dexibuprofen is indicated for the treatment aspirin24. Ibuprofen was a potential cause of of Pain and inflammation caused by GI bleeding25,26,increasing the risk of gastric osteoarthritis ulcers and damage, renal failure, epistaxis27- Acute symptomatic treatment of pain 30,apoptosis31, heart failure, during menstrual bleeding (Primary hyperkalaemia32, confusion and dysmenorrhoea)Mild to moderate pain, bronchospasm33.It has been estimated that such as pain in the muscles and joints and 1 in 5 chronic users (lasting over a long toothaches. It may be used as an antipyretic period of time) of NSAIDs will develop to reduce fever. gastric damage which can be silent34. Other adverse effects of ibuprofen have Contra-indications been reported less frequently. They include Dexibuprofen should not be administered thrombocytopenia, rashes, headache, to Patients with hypersensitivity dizziness, blurred vision and in few cases toDexibuprofen or other non-steroidal anti- toxic amblyopia, fluid retention and edema. inflammatory drugs, Patients with active or Patients who develop ocular disturbances suspected gastrointestinal ulcer or history should discontinue the use of of recurrent gastrointestinal ulcer,Patients dexibuprofen35. Effects on kidney (as with who have gastrointestinal bleeding or other all NSAIDs) include acute renal failure, active bleedings or bleeding disorders, interstitial nephritis, and nephritic Patients with active Crohn's disease or syndrome, but these very rarely occur36. active ulcerative colitis, Patients with severe renal dysfunction (GFR < Drug-Drug Interactions 30ml/min),Patients with severely impaired Dexibuprofen has established drug hepatic function, Patients with hemorrhagic interactions with NSAIDs which are both diathesis and other coagulation disorders, pharmacokinetic or pharmacodynamic in or patients receiving anticoagulant therapy, origin(37,38). The most potentially serious From the beginning of 6th month of interactions include the use of NSAIDs with pregnancy. lithium, warfarin, oral hypoglycemics, high dose methotrexate, antihypertensives, Precautions angiotensin converting enzyme inhibitors, Symptoms or history of gastro-intestinal β-blockers, and diuretics. Anticipation and disease, asthma, impaired hepatic, cardiac care full monitoring can often prevent or renal function. NSAID may mask serious events when these drugs are used