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Biodisposition in Relation to Actions

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Ibuprofen: Pharmacology, Therapeutics and Side Effects

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Abstract

The biodisposition and metabolism of ibuprofen are important for understanding its applications, mode of actions and safety in various inflammatory and painful conditions where it is widely used. Ibuprofen is metabolised via oxidative—cytochrome P450 2C9, 2C19 and 2C8 (phase I)—and conjugation (phase II) pathways. The drug has a relatively short plasma elimination half-life and this is a feature in relation to its relative safety. The drug rapidly accumulates in synovial fluids and other compartments where it acts to control pain and inflammation. The pharmacokinetics of ibuprofen is closely related to its therapeutic effects in adults and children. There is relatively little variation in pharmacokinetics of ibuprofen in different inflammatory conditions, with relatively limited increases in plasma concentrations in moderate liver and renal diseases.

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References

  • Aarons L, Grennan DM, Rajapakse C, Brinkley J, Siddiqui M, Taylor L, Higham C (1983) Anti-inflammatory (ibuprofen) drug therapy in rheumatoid arthritis–rate of response and lack of time dependency of plasma pharmacokinetics. Br J Clin Pharmacol 15:387–388

    Article  PubMed  CAS  Google Scholar 

  • Adams SS, Breslof P, Mason CG (1976) Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of the (−)-isomer. J Pharm Pharmacol 28:256–257

    Article  PubMed  CAS  Google Scholar 

  • Aiache JM (1990) French and/or European perspectives on biopharmaceutical characterization of drug dosage forms. J Pharm Biomed Anal 8:499–506

    Article  PubMed  CAS  Google Scholar 

  • Albert KS, Gernaat CM (1984) Pharmacokinetics of ibuprofen. Am J Med 77:40–46

    Article  PubMed  CAS  Google Scholar 

  • Albert KS, Gillespie WR, Wagner JG, Pau A, Lockwood GF (1984) Effects of age on the clinical pharmacokinetics of ibuprofen. Am J Med 77(1A):47–50

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Thomas R (2006) Systematic review: intravenous Ibuprofen in preterm newborns. Semin Perinatol 30:114–120

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Varvarigou A, Beharry K, Bansal R, Bardin C, Modanlou H, Papageorgiou A, Chemtob S (1997) Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr 86:289–293

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Beharry KD, Valencia GB (2009a) Nonsteroidal anti-inflammatory drugs (NSAIDs) in the newborn—which ones? J Matern Fetal Neonatal Med 22(Suppl 3):21–22

    Article  PubMed  CAS  Google Scholar 

  • Aranda JV, Clyman R, Cox B, Van Overmeire B, Wozniak P, Sosenko I, Carlo WA, Ward RM, Shalwitz R, Baggs G, Seth A, Darko L (2009b) A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants. Am J Perinatol 26:235–245

    Article  PubMed  Google Scholar 

  • Arranz I, Martín-Suárez A, Lanao JM, Mora F, Vázquez C, Escribano A, Juste M, Mercader J, Ripoll E (2003) Population pharmacokinetics of high dose ibuprofen in cystic fibrosis. Arch Dis Child 88:1128–1130

    Article  PubMed  CAS  Google Scholar 

  • Autret-Leca E (2003) A general overview of the use of ibuprofen in paediatrics. Int J Clin Pract Suppl (135):9–12

    Google Scholar 

  • Averbuch M, Katzper M (2003) A search for sex differences in response to analgesia. Arch Intern Med 160:3424–3428

    Article  Google Scholar 

  • Bannwarth B, Lapicque F, Pehourcq F, Gillet P, Schaeverbeke T, Laborde C, Dehais J, Gaucher A, Netter P (1995) Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal fluid. Br J Clin Pharmacol 40:266–269

    Article  PubMed  CAS  Google Scholar 

  • Barden J, Edwards JE, McQuay HJ, Wiffen PJ, Moore RA (2004) Relative efficacy of oral analgesics after third molar extraction. Br Dent J 197(7):407–411

    Article  PubMed  CAS  Google Scholar 

  • Bjørnsson GA, Haanaes HR, Skoglund LA (2003) A randomized, double-blind crossover trial of paracetamol 1000 mg four times daily vs. ibuprofen 600 mg: effect on swelling and other postoperative events after third molar surgery. Br J Clin Pharmacol 55:405–412

    Article  PubMed  Google Scholar 

  • Boureau F (1998) Multicentre study of the efficacy of ibuprofen compared with paracetamol in throat pain associated with tonsillitis. In: Rainsford KD, Powanda MC (eds) Safety and efficacy of non-prescription (OTC) analgesics and NSAIDs. Kluwer Academic, Dordrecht, pp 119–121

    Google Scholar 

  • Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI (1992) Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal anti-inflammatory drug or pure analgesic. J Rheumatol 19:1950–1954

    PubMed  CAS  Google Scholar 

  • Brocks D, Jamali F (1999) The pharmacokinetics of ibuprofen in humans and animals. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 89–142

    Google Scholar 

  • Brown RD, Wilson JT, Kearns GL, Eichler VF, Johnson VA, Bertrand KM (1992) Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children. J Clin Pharmacol 32:231–241

    PubMed  CAS  Google Scholar 

  • Brune K (2007) Persistence of NSAIDs at effect sites and rapid disappearance from side-effect compartments contributes to tolerability. Curr Med Res Opin 23:2985–2995

    Article  PubMed  CAS  Google Scholar 

  • Brunton L, Parker K, Blumenthal D, Buxton I (2008) Goodman and Gilman’s manual of pharmacology and therapeutics. McGraw Hill Medical, New York

    Google Scholar 

  • Buchheit D, Dragan CA, Schmitt EI, Bureik M (2011) Production of ibuprofen acyl glucuronides by human UGT2B7. Drug Metab Dispos 39:2174–2181

    Article  PubMed  CAS  Google Scholar 

  • Castillo M, Lam YW, Dooley MA, Stahl E, Smith PC (1995) Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly. Clin Pharmacol Ther 57:636–644

    Article  PubMed  CAS  Google Scholar 

  • Cattaneo D, Clementi E (2010) Clinical pharmacokinetics of ibuprofen arginine. Curr Clin Pharmacol 5(4):239–245

    Article  PubMed  CAS  Google Scholar 

  • Ceppi Monti N, Gazzaniga A, Gianesello V, Stroppolo F, Lodola E (1992) Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen. Arzneimittelforschung 42(4):556–559

    PubMed  CAS  Google Scholar 

  • Codispoti JR, Prior MJ, Fu M, Harte CM, Nelson EB (2001) Efficacy of non-prescription doses of ibuprofen for treating migraine headache. A randomized controlled trial. Headache 41:665–679

    Article  PubMed  CAS  Google Scholar 

  • Cooper SA (1984) Five studies on ibuprofen for postsurgical dental pain. Am J Med 77(1A):70–77

    Google Scholar 

  • Cox SR, Gall EP, Forbes KK, Gresham M, Goris G (1991) Pharmacokinetics of the R(-) and S(+) enantiomers of ibuprofen in the serum and synovial fluid of arthritis patients. J Clin Pharmacol 31(1):88–94

    PubMed  CAS  Google Scholar 

  • Crockford DJ, Maher AD, Ahmadi KR, Barrett A, Plumb RS, Wilson ID, Nicholson JK (2008) 1H NMR and UPLC-MSE statistical heterospectroscopy: characterization of drug metabolites (xenometabolome) in epidemiological studies. Anal Chem 80:6835–6844

    Article  PubMed  CAS  Google Scholar 

  • Daniels S, Reader S, Berry P, Goulder M (2009) Onset of analgesia with sodium ibuprofen, ibuprofen acid incorporating poloxamer and acetaminophen–a single-dose, double-blind, placebo-controlled study in patients with post-operative dental pain. Eur J Clin Pharmacol 65:343–353

    Article  PubMed  CAS  Google Scholar 

  • Daniels SE, Goulder MA, Aspley S, Reader S (2011) A randomised, five-parallel group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain. Pain 152:632–642

    Article  PubMed  CAS  Google Scholar 

  • Davies NM (1998) Clinical pharmacokinetics of ibuprofen. Clin Pharmacokinet 34:101–154

    Article  PubMed  CAS  Google Scholar 

  • Day RO, Williams KM, Graham GG, Lee EJ, Knihinicki RR, Champion GD (1988) Stereoselective disposition of ibuprofen enantiomers in synovial fluid. Clin Pharmacol Ther 43:480–487

    Article  PubMed  CAS  Google Scholar 

  • Dewland PM, Reader S, Berry P (2009) Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers. BMC Clin Pharmacol 9:19

    Article  PubMed  CAS  Google Scholar 

  • Diener HC, Bussone G, de Liano H, Eikermann A, Englert R, Floeter T, Gallai V, Gobel H, Hartung E, Jimenez MD, Lange R, Manzoni GC, Mueller-Schwefe G, Nappi G, Pinessi L, Prat J, Puca FM, Titus F, Voelker M (2004) Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks. Cephalalgia 24:947–954

    Article  PubMed  CAS  Google Scholar 

  • Dionne RA (1998) Evaluation and analgesic mechanisms and NSAIDs for acute pain using the oral surgery model. In: Rainsford KD, Powanda MC (eds) Safety and efficacy of non-prescription (OTC) analgesics and NSAIDs. Kluwer Academic, Dordrecht, pp 105–117

    Chapter  Google Scholar 

  • Dionne RA, Cooper SA (1999) Use of ibuprofen in dentistry. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 409–430

    Google Scholar 

  • Dominkus M, Nicolakis M, Kotz R, Wilkinson FE, Kaiser RR, Chlud K (1996) Comparison of tissue and plasma levels of ibuprofen after oral and topical administration. Arzneimittelforschung 46:1138–1143

    PubMed  CAS  Google Scholar 

  • Dong JQ, Ni L, Scott CS, Retsch-Bogart GZ, Smith PC (2000) Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis. J Clin Pharmacol 40(8):861–868

    Article  PubMed  CAS  Google Scholar 

  • Eller MG, Wright C III, Della-Coletta AA (1989) Absorption kinetics of rectally and orally administered ibuprofen. Biopharm Drug Dispos 10:269–278

    Article  PubMed  CAS  Google Scholar 

  • Elmquist WF, Chan KK, Sawchuk RJ (1994) Transsynovial drug distribution: synovial mean transit time of diclofenac and other nonsteroidal antiinflammatory drugs. Pharm Res 11(12):1689–1697

    Article  PubMed  CAS  Google Scholar 

  • Florence AT, Attwood D (1998) Physicochemical principles in pharmacy, 3rd edn. Macmillan, Houndmills Basingstoke, pp 441–446

    Google Scholar 

  • Gallo JM, Gall EP, Gillespie WR, Albert KS, Perrier D (1986) Ibuprofen kinetics in plasma and synovial fluid of arthritic patients. J Clin Pharmacol 26(1):65–70

    PubMed  CAS  Google Scholar 

  • Garg V, Jusko WJ (1994) Pharmacodynamic modelling of nonsteroidal anti-inflammatory drugs: antipyretic effect of ibuprofen. Clin Pharmacol Ther 55:87–88

    Article  PubMed  CAS  Google Scholar 

  • Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K (1989) The therapeutic relevant differences in the pharmacokinetical and pharmaceutical behaviours of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol 27:324–328

    PubMed  CAS  Google Scholar 

  • Geisslinger G, Stock KP, Loew D, Bach GL, Brune K (1993) Variability in the stereoselective disposition of ibuprofen in patients with rheumatoid arthritis. Br J Pharmacol 35:603–607

    Article  CAS  Google Scholar 

  • Glass RC, Swannell AJ (1978) Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis. Br J Clin Pharmacol 6:453P–454P

    Article  PubMed  CAS  Google Scholar 

  • GÅ‚owka FK (2000) Stereoselective pharmacokinetics of ibuprofen and its lysinate from suppositories in rabbits. Int J Pharm 199:159–166

    Article  PubMed  Google Scholar 

  • Graham GG (1988) Kinetics of non-steroidal anti-inflammatory drugs in synovial fluid. In: Brooks PM, Day RO, Williams K, Graham G (eds) Basis for variability of response to anti-rheumatic drugs. Brikhäuser, Bael, pp 66–75

    Google Scholar 

  • Graham GG, Scott KF (2003) Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology 11:401–413

    Article  PubMed  CAS  Google Scholar 

  • Graham GG, Williams KM (2004) Metabolism and pharmacokinetics of ibuprofen. In: Rainsford KD (ed) Aspirin and related drugs. Taylor & Francis, London, pp 157–180

    Google Scholar 

  • Grennan DM, Aarons L, Siddiqui M, Richards M, Thompson R, Higham C (1983) Dose-response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings. Br J Clin Pharmacol 15(3):311–316

    Article  PubMed  CAS  Google Scholar 

  • Grillo MP, Hua F (2008) Enantioselective formation of ibuprofen-S-acyl-glutathione in vitro in incubation of ibuprofen with rat hepatocytes. Chem Res Toxicol 21:1749–1759

    Article  PubMed  CAS  Google Scholar 

  • Growcott JW, Stone A, Beise R, Stammer H, Tetzloff W, Demey C (2000) Sensitivity of repeated interdigital web pinching to detect antinociceptive effects of ibuprofen. Br J Clin Pharmacol 49:331–336

    Article  PubMed  CAS  Google Scholar 

  • Hamman MA, Thompson GA, Hall SD (1997) Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem Pharmacol 54:33–41

    Article  PubMed  CAS  Google Scholar 

  • Henry D, Lim LL-Y, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, Savage R, Logan R, Moride Y, Hawkey C et al (1996) Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. Br Med J 312:1563–1566

    Article  CAS  Google Scholar 

  • Henry DA, Drew A, Beuzeville S (1998) Adverse drug reactions in the gastrointestinal system attributed to ibuprofen. In: Rainsford KD, Powanda MC (eds) Safety and efficacy of non-prescription (OTC) analgesics and NSAIDs. Kluwer Academic, Dodrecht, pp 19–45

    Chapter  Google Scholar 

  • Hermann TW, Gtówka FK, Garrett ER (1993) Bioavailability of racemic ibuprofen and its lysine from suppositories in rabbits. J Pharm Sci 82:1102–1111

    Article  PubMed  CAS  Google Scholar 

  • Hersh EV, Moore PA, Ross GL (2000a) Over-the-counter analgesics and antipyretics: a critical assessment. Clin Ther 22:500–548

    Article  PubMed  CAS  Google Scholar 

  • Holmes E, Loo RL, Cloarec O, Coen M, Tang H, Maibaum E, Bruce S, Chan Q, Elliott P, Stamler J, Wilson ID, Lindon JC, Nicholson JK (2007) Detection of urinary drug metabolite (xenometabolome) signatures in molecular epidemiology studies via statistical total correlation (NMR) spectroscopy. Anal Chem 79:2629–2640

    Article  PubMed  CAS  Google Scholar 

  • Ikegawa S, Murao N, Oohashi J, Goto J (1998) Separatory determination of diastereomeric ibuprofen glucuronides in human urine. Biomed Chromatogr 12:317–321

    Article  PubMed  CAS  Google Scholar 

  • Jacqz-Aigrain E, Anderson BJ (2006) Pain control: non-steroidal anti-inflammatory agents. Semin Fetal Neonat Med 11:251–259

    Article  Google Scholar 

  • Jain AK, Ryan JR, McMahon FG, Kuebel JO, Walters PJ, Noveck C (1986) Analgesic efficacy of low-dose ibuprofen in dental extraction pain. Pharmacotherapy 6(6):318–322

    PubMed  CAS  Google Scholar 

  • Jamali F, Aghazadeh-Habashi A (2008) Rapidly dissolving formulations for quick absorption during pain episodes: ibuprofen. Int J Clin Pharmacol Ther 46:55–63

    PubMed  CAS  Google Scholar 

  • Jamali F, Kunz-Dober CM (1999) Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreases serum enantiomer concentration after dental surgery. Br J Clin Pharmacol 47:391–396

    Article  PubMed  CAS  Google Scholar 

  • Johnson CH, Wilson ID, Harding JR, Stachulski AV, Iddon L, Nicholson JK, Lindon JC (2007) NMR spectroscopic studies on the in vitro glucuronide migration kinetics of ibuprofen ((+/-)-(R, S)-2-(4-sobutylphenyl) propanoic acid), its metabolites and analogues. Anal Chem 79:8720–8727

    Article  PubMed  CAS  Google Scholar 

  • Jones K, Seymour RA, Hawkesford JE (1997) Are the pharmacokinetics of ibuprofen important determinants for the drug’s efficacy in postoperative pain after third molar surgery? Br J Oral Maxillofac Surg 35:173–176

    Article  PubMed  CAS  Google Scholar 

  • Kaka JS, Tekle A (1992) Bioavailability of ibuprofen from oral and suppository preparations in rats. Res Commun Chem Pathol Pharmacol 76:171–182

    PubMed  CAS  Google Scholar 

  • Kauffman RE, Nelson MV (1992) Effect of age on ibuprofen pharmacokinetics and antipyretic response. J Pediatr 121:969–973

    Article  PubMed  CAS  Google Scholar 

  • Kean WF, Buchanan WW, Rainsford KD (1999) Therapeutics of ibuprofen in rheumatic and other chronic and painful diseases. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 279–353

    Google Scholar 

  • Kelley MT, Walson PD, Edge JH, Cox S, Mortensen ME (1992) Pharmacokinetics and pharmacodynamic of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther 52:181–189

    Article  PubMed  CAS  Google Scholar 

  • Kirchheiner J, Meineke I, Freytag G, Meisel C, Roots I, Brockmöller J (2002) Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther 72(1):62–75

    Article  PubMed  CAS  Google Scholar 

  • Kobal G, Hummel C, Gruber M, Geisslinger G, Hummel T (1994) Dose-related effects of ibuprofen on pain-related potentials. Br J Clin Pharmacol 37:445–452

    Article  PubMed  CAS  Google Scholar 

  • Koga T, Fujiwara R, Nakajima M, Yokoi T (2011) Toxicological evaluation of acyl glucuronides of nonsteroidal anti-inflammatory drugs using human embryonic kidney 293 cells stably expressing human UDP-glucuronyltransferase and human hepatocytes. Drug Metab Dispos 39:54–60

    Article  PubMed  CAS  Google Scholar 

  • Konstan MW, Hoppel CL, Chai BL, Davis PB (1991) Ibuprofen in children with cystic fibrosis: pharmacokinetics and adverse effects. J Pediatr 118:956–964

    Article  PubMed  CAS  Google Scholar 

  • Konstan MW, Byard PJ, Hoppel CL, Davis PB (1995) Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med 332:848–854

    Article  PubMed  CAS  Google Scholar 

  • Kyllönen M, Olkkola KT, Seppälä T, Ryhänen P (2005) Perioperative pharmacokinetics of ibuprofen enantiomers after rectal administration. Paediatr Anaesth 15:566–573

    Article  PubMed  Google Scholar 

  • Lange R, Lentz R (1995) Comparison of ketoprofen, ibuprofen and naproxen sodium in the treatment of tension-type headache. Drugs Exp Clin Res 21:89–96

    PubMed  CAS  Google Scholar 

  • Laska EM, Sunshine A, Marrero I, Olson N, Siegel C, McCormick N (1986) The correlation between blood levels of ibuprofen and clinical analgesic response. Clin Pharmacol Ther 40:1–7

    Article  PubMed  CAS  Google Scholar 

  • Li Wan Po AW (2006) Dose-response of minor analgesics in acute pain. Br J Clin Pharmacol 63:268–270

    PubMed  Google Scholar 

  • Lindh JD, Lundgren S, Holm L, Alfredsson L, Rane A (2005) Several-fold increase in risk of overanticoagulation by CYP2C9 mutations. Clin Pharmacol Ther 78:540–550

    Article  PubMed  CAS  Google Scholar 

  • Lötsch J, Muth-Selbach U, Tegeder I, Brune K, Geisslinger G (2001) Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate. Br J Clin Pharmacol 52:387–398

    Article  PubMed  Google Scholar 

  • Makela AL, Lempiainen YT (1979) Ibuprofen in the treatment of juvenile rheumatoid arthritis: metabolism and concentrations in synovial fluid. Br J Clin Pract (Suppl) 23–27

    Google Scholar 

  • Mäkelä AL, Lempiäinen M, Ylijoki H (1981) Ibuprofen levels in serum and synovial fluid. Scand J Rheumatol Suppl 39:15–17

    Article  PubMed  Google Scholar 

  • Malmstrom K, Sapre A, Couglin H, Agrawal NG, Mazenko RS, Fricke JR Jr (2004) Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Clin Ther 26:667–679

    Article  PubMed  CAS  Google Scholar 

  • McQuay HJ, Moore RA (2007) Dose-response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies. Br J Clin Pharmacol 63:271–278

    Article  PubMed  CAS  Google Scholar 

  • Mo S-L, Zhou Z-W, Yang L-P, Wei MQ, Zhou S-F (2009) New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part 1. Curr Drug Metab 10:1075–1126

    Article  PubMed  CAS  Google Scholar 

  • Moore RA, Derry S, McQuay HJ, Wiffen PJ (2011) Single dose oral analgesics for acute postoperative pain in adults (Review). The Cochrane Collaboration. Cochrane Database Syst Rev (9):CD008659. doi:10.1002/14651858.CD008659.pub2.Chichester

  • Moore RA, Derry S, McQuay HJ, Wiffen PJ (2011). Single dose oral analgesics for acute postoperative pain in adults. Cochrane Database Syst Rev (9). http://www.thecochranelibrary.com

  • Nelson SL, Brahim JS, Korn SH, Greene SS, Suchower LJ (1994) Comparison of single-dose ibuprofen lysine, acetylsalicylic acid, and placebo for moderate-to-severe postoperative dental pain. Clin Ther 16:458–465

    PubMed  CAS  Google Scholar 

  • Nielsen JC, Bjerring P, Arendt-Nielsen L, Petterson KJ (1990) A double-blind, placebo controlled, cross-over comparison of the analgesic effect of ibuprofen 400 mg and 800 mg on laser-induced pain. Br J Clin Pharmacol 30:711–715

    Article  PubMed  CAS  Google Scholar 

  • Noro S, Komatsu Y, Uesugi T (1982a) Studies on pharmaceutical drug design for suppositories. I. Effect of physicochemical properties of surfactants and polymers on emulsion-type bases. Chem Pharm Bull (Tokyo) 30:2900–2905

    Article  CAS  Google Scholar 

  • Noro S, Komatsu Y, Uesugi T (1982b) Studies on pharmaceutical drug design for suppositories. II. Rheological properties of emulsion-type suppository bases. Chem Pharm Bull (Tokyo) 30(8):2906–2911

    Google Scholar 

  • Orme MCL’E (1990) Plasma concentrations and the therapeutic effect of anti-inflammatory and anti-rheumatic drugs. In: Orme M (ed) Anti-rheumatic drugs. Pergamon, New York, pp 217–233

    Google Scholar 

  • Pachkoria K, Lucena MI, Ruiz-Cabello F, Crespo E, Cabello MR, Andrade RJ, Spanish Group for the Study of Drug-Induced Liver Disease (Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos) (2007a) Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI). Br J Pharmacol 150:808–815

    Article  PubMed  CAS  Google Scholar 

  • Pachkoria K, Lucena MI, Molokhia M, Cueto R, Carbollo AS, Carvajal A, Andrade RJ (2007b) Genetic and molecular factors in drug-induced liver injury: a review. Curr Drug Saf 2:281–286

    Article  Google Scholar 

  • Packman B, Packman E, Doyle G, Cooper S, Ashraf E, Koronkiewicz K, Jayawardena S (2000) Solubilized ibuprofen: evaluation of onset, relief, and safety of a novel formulation in the treatment of episodic tension-type headache. Headache 40:561–567

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD (1996) Mode of action, uses and side-effects of anti-rheumatic drugs. In: Rainsford KD (ed) Advances in anti-rheumatic therapy. CRC, Boca Raton, FL, pp 59–111

    Google Scholar 

  • Rainsford KD (1999a) History and development of ibuprofen. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 3–24

    Chapter  Google Scholar 

  • Rainsford KD (1999b) Pharmacology and toxicology of ibuprofen. In: Rainsford KD (ed) Ibuprofen: a critical bibliographic review. Taylor & Francis, London, pp 145–275

    Chapter  Google Scholar 

  • Rainsford KD (2009) Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology 17:275–342

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD, Kean WF, Ehrlich GE (2008a) Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine. Curr Med Res Opin 24:2967–2992

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD, Kean WF, Ehrlich GE (2008b) Triad (GI, CV, Hepatic) composite toxicity ratings for use in assessing the overall safety of NSAIDs. Intern Med J 38(suppl 2):A32 (Abstract No. ARP71)

    Google Scholar 

  • Rang HP, Dale MM, Ritter JM, Moore PK (2003) Pharmacology, 5th edn. Churchill-Livingstone, Edinburgh

    Google Scholar 

  • Rau R, Berner G, Wagener HH, Vögtle-Junkert U (1989) Konzentrationen von Ibuprofemn und Eiweiβ-Gehalt sowie pH-Wert in Kniegelenkserguβ und plasma nach oraler Gabe von Ibuprofen bei Arthritis-Patienten. Arzneim-Forsch 39:1166–1168

    CAS  Google Scholar 

  • Re E, Pariente-Khayat A, Gouyet L, Vauzelle-Kervroëdan F, Pons G, D’Athis Ph, Dubois MC, Murat I, Lassale C, Goehrs M, Cl Sainst-Maurice, Olive G (1994) Stereoselective disposition of ibuprofen enantiomers in infants. Br J Clin Pharmacol 38:375–378

    Google Scholar 

  • Reichel C, Brugger R, Bang H, Geisslinger G, Brune K (1997) Molecular cloning and expression of a 2-arylpropionyl-Coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. Mol Pharmacol 51:576–582

    PubMed  CAS  Google Scholar 

  • Rudy AC, Bradley JD, Ryan SI, Kalasinski LA, Xiaotao Q, Hall SD (1992) Variability in the disposition of ibuprofen enantiomers in osteoarthritis patients. Ther Drug Monit 14:464–470

    Article  PubMed  CAS  Google Scholar 

  • Sandrini G, Franchini S, Lanfranchi S, Granella F, Manzoni GC, Nappi G (1998) Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks. Int J Clin Pharmacol Res 18:145–150

    PubMed  CAS  Google Scholar 

  • Schachtel BP, Fillingim JM, Thoden WR, Lane AC, Baybutt RI (1988) Sore throat pain in the evaluation of mild analgesics. Clin Pharmacol Ther 44:704–711

    Article  PubMed  CAS  Google Scholar 

  • Schachtel BP, Cleves GS, Konerman JP, Brown AT, Markham AO (1994) A placebo-controlled model to assay the onset of action of nonprescription-strength analgesic drugs. Clin Pharmacol Ther 55:464–470

    Article  PubMed  CAS  Google Scholar 

  • Schachtel BP, Furey SA, Thoden WR (1996) Nonprescription ibuprofen and acetaminophen in the treatment of tension-type headache. J Clin Pharmacol 36:1120–1125

    PubMed  CAS  Google Scholar 

  • Schachtel BP, Pan S, Kohles JD, Sanner KM, Schachtel EP, Bey M (2007) Utility and sensitivity of the sore throat pain model: results of a randomized controlled trial on the COX-2 selective inhibitor valdecoxib. J Clin Pharmacol 47:860–870

    Article  PubMed  CAS  Google Scholar 

  • Schleier P, Prochnau A, Schmidt-Westhausen AM, Peters H, Becker J, Latz T, Jackowski J, Peters EU, Romanos GE, Zahn B, Ludemann J, Maares J, Petersen B (2007) Ibuprofen sodium dihydrate, an ibuprofen formulation with improved absorption characteristics, provides faster and greater pain relief than ibuprofen acid. Int J Clin Pharmacol Ther 45:89–97

    PubMed  CAS  Google Scholar 

  • Schou S, Nielsen H, Nattestad A, Hillerup S, Ritzau M, Branebjerg PE, Bugge C, Skoglund LA (1998) Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: a single-dose, randomized, placebo-controlled, and double-blind study of 304 patients. J Clin Pharmacol 38:447–454

    PubMed  CAS  Google Scholar 

  • Seibel K, Schaffler K, Reeh P, Reitmeir P (2004) Comparison of two different preparations of ibuprofen with regard to the time course of their analgesic affect. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from UW-irritated skin in healthy volunteers. Arzneimittelforsch 54:444–451

    PubMed  CAS  Google Scholar 

  • Seideman P, Graham GG, Lohrer F, Duncan MW, Williams KM, Day RO (1994) The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid. Br J Clin Pharmacol 38:221–227

    Article  PubMed  CAS  Google Scholar 

  • Seymour RA, Hawkesford JE, Weldon M, Brewster A (1991) An evaluation of different ibuprofen preparations in the control of postoperative pain after third molar surgery. Br J Clin Pharmacol 31:83–87

    Article  PubMed  CAS  Google Scholar 

  • Seymour RA, Ward-Booth P, Kelly PJ (1996) Evaluation of different doses of soluble ibuprofen and ibuprofen tablets in postoperative dental pain. Br J Oral Maxillofac Surg 34(1):110–114

    Article  PubMed  CAS  Google Scholar 

  • Seymour RA, Frame J, Negus TW, Hawkesford JE, Marsden J, Matthew IR (1998) The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery. Br J Oral Maxillofac Surg 36:375–379

    Article  PubMed  CAS  Google Scholar 

  • Seymour RA, Hawkesford JE, Hill CM, Frame J, Andrews C (1999) The efficacy of a novel adenosine agonist (WAG 994) in postoperative dental pain. Br J Clin Pharmacol 47:675–680

    Article  PubMed  CAS  Google Scholar 

  • Shah A, Woodruff M, Agarwal V, Liu P, Sundaresan P (2001) Pharmacokinetics, safety, and tolerability of BAY 12-9566 and non-steroidal anti-inflammatory agents (naproxen, ibuprofen) during coadministration in patients with osteoarthritis. J Clin Pharmacol 41:330

    Article  PubMed  CAS  Google Scholar 

  • Sharma PK, Garg SK, Narang A (2003) Pharmacokinetics of oral ibuprofen in premature infants. J Clin Pharmacol 43:968–973

    Article  PubMed  CAS  Google Scholar 

  • Speed WC, Kang SP, Tuck DP, Harris LN, Kidd KK (2009) Global variation in CYP2C8–CYP2C9 functional haplotypes. Pharmacogenomics J 9:283–290

    Article  PubMed  CAS  Google Scholar 

  • Suri A, Grundy BL, Derendorf H (1997a) Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and flurbiprofen after oral administration. Int J Clin Pharmacol Ther 35:1–8

    PubMed  CAS  Google Scholar 

  • Suri A, Estes KS, Geisslinger G, Derendorf H (1997b) Pharmacokinetic-pharmacodynamic relationships for analgesics. Int J Pharmacol Ther 35:307–323

    CAS  Google Scholar 

  • Sycha T, Gustorff B, Lehr S, Tanew A, Eichler HG, Schmetterer L (2003) A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects. Br J Clin Pharmacol 56:165–172

    Article  PubMed  CAS  Google Scholar 

  • Troconiz I, Armenteros S, Planelles MV, Benitez J, Calvo R, Dominguez R (2000) Pharmacokinetic-pharmacodynamic modelling of the antipyretic effect of two oral formulations of ibuprofen. Clin Pharmacokinet 38:505–518

    Article  PubMed  CAS  Google Scholar 

  • Van Hoogdalem EJ, de Boer AG, Breimer DD (1991) Pharmacokinetics of rectal drug administration, Part II. Clinical applications of peripherally acting drugs, and conclusions. Clin Pharmacokinet 21:110–128

    Article  PubMed  Google Scholar 

  • Van Overmeire B, Touw D, Schepens PJ, Kearns GL, van den Anker JN (2001) Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther 70:336–343

    PubMed  Google Scholar 

  • Vanderhoeven SJ, Lindon JC, Troke J, Nicholson JK, Wilson ID (2006) NMR spectroscopic studies of the transacylation reactivity of ibuprofen 1-beta-O-acyl-glucuronide. J Pharm Biomed Anal 41:1002–1006

    Article  PubMed  CAS  Google Scholar 

  • Viitanen H, Tuominen N, Vääräniemi H, Nikanne E, Annila P (2003) Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case administration. Br J Anaesthes 91:363–367

    Article  CAS  Google Scholar 

  • Walker JS, Carmody JJ (1998) Experimental pain in healthy human subjects: gender differences in nociception and in response to ibuprofen. Anesth Analg 86:1257–1262

    PubMed  CAS  Google Scholar 

  • Walker JS, Arroyo JF, Nguyen T, Day RO (1993a) Analgesic efficacy of non-steroidal anti-inflammatory drugs in experimental pain in humans. Br J Clin Pharmacol 36:417–425

    Article  PubMed  CAS  Google Scholar 

  • Walker JS, Knihinicki RD, Seideman P, Day RO (1993b) Pharmacokinetics of ibuprofen enantiomers in plasma and suction blister fluid in healthy volunteers. J Pharm Sci 82:787–790

    Article  PubMed  CAS  Google Scholar 

  • Wallis WJ, Simpkin PA (1983) Antirheumatic drug concentrations in human synovial fluid and synovial tissue: observations on extravascular pharmacokinetics. Clin Pharmacokinet 8:496–522

    Article  PubMed  CAS  Google Scholar 

  • Walson PD, Galletta G, Braden NJ, Alexander L (1989) Ibuprofen, acetaminophen, and placebo treatment of febrile children. Clin Pharmacol Ther 46:9–17

    Article  PubMed  CAS  Google Scholar 

  • Wanwimolruk S, Brooks PM, Birkett DJ (1983) Protein binding of non-steroidal anti-inflammatpry drugs in plasma and synovial fluid of arthritic patients. Br J Clin Pharmacol 15:91–94

    Article  PubMed  CAS  Google Scholar 

  • Whitlam JB, Brown KF, Crooks MJ, Room GF (1981) Transsynovial distribution of ibuprofen in arthritic patients. Clin Pharmacol Ther 29(4):487–492

    Article  PubMed  CAS  Google Scholar 

  • Williams K, Day R, Knihinicki R, Duffield A (1986) The stereoselective uptake of ibuprofen enantiomers into adipose tissue. Biochem Pharmacol 35(19):3403–3405

    Article  PubMed  CAS  Google Scholar 

  • Yong CS, Oh YK, Jung SH, Rhee JD, Kim HD, Kim CK, Choi HG (2004) Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol. Eur J Pharm Sci 23:347–353

    Article  PubMed  CAS  Google Scholar 

  • Zhang WY, Li Wan Po A (1998) Efficacy of minor analgesics in primary dysmenorrhoea: a systematic review. Br J Obstet Gynecol 105:780–789

    Article  CAS  Google Scholar 

  • Cooper SA, Schachtel BP, Goldman E, Gelb S, Cohn P (1989) Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 29:1026–1030

    PubMed  CAS  Google Scholar 

  • Dionne RA, Cooper SA (1978) Evaluation of preoperative ibuprofen for postoperative pain after removal of third molars. Oral Surg Oral Med Oral Pathol 45:851–856

    Article  PubMed  CAS  Google Scholar 

  • Hadas D, Youngster I, Cohen A, Leibovitch E, Shavit I, Erez I, Uziel Y, Berkovitch M (2011) Premarketing surveillance of ibuprofen suppositories in febrile children. Clin Pediatr (Phila) 50:196–199

    Article  Google Scholar 

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    K. D. Rainsford

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Rainsford, K.D. (2012). Biodisposition in Relation to Actions. In: Ibuprofen: Pharmacology, Therapeutics and Side Effects. Springer, Basel. https://doi.org/10.1007/978-3-0348-0496-7_2

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