Efficacy, Safety, Quality Assurance of Isomers of Non-Steroidal Anti-Inflammatory Drugs: Dexketoprofen and Dexibuprofen

Elena Litvinova, Mariya Zarichkova, Svitlana Kovalenko, Olga Posylkina, Olena Tkachenko, Anastasiia Lisna

Abstract

The aim of this work is to analyze and systematize data on efficacy, safety, and quality assurance for NSAID isomers – dexketoprofen and dexibuprofen. Studies were conducted using databases on the Internet: PubMed; Food and Drug Administration, European Medicines Agency. It has used retrospective, logical, systematic and analytical methods. The results of a multifaceted analysis of sources of data of clinical use proved the high analgesic efficacy of dexketoprofen and dexibuprofen in acute and chronic pain of various etiologies, such as toothache, dysmenorrhea, pain after surgery, muscle pain, headache, back pain, pain from bone metastases, etc. To achieve the effect obtained with the use of 1 dose of racemic NSAIDs, half the dose of their active isomers is sufficient. The high clinical effectiveness of dexketoprofen, dexibuprofen combines with their relative tolerance, in particular from the gastrointestinal tract. In large part, the safety of dexketoprofen is due to the presence of only the active S (+) - enantiomer of ketoprofen, dexibuprofen is due to the presence of only active S (+) - ibuprofen, which eliminates the side effects associated with the influence of the R (-) - enantiomers.
The results of the analysis of quality assurance of generic dexketoprofen (class 1 of biopharmaceutical classification system) and dexibuprofen (class 2 of biopharmaceutical classification system) during the biowaiver procedure are systematized. It has been shown that not only high permeability and high solubility, but also the composition of the drug excipients are important for pharmaceutical equivalence in vitro. Based on the results research findings presented, it is possible to optimize the technological process and analytical methods, which allows taking into account critical factors and ensuring the quality of the medicine and its bioequivalence to the reference drug.

Full Text:

PDF

References

Felson DT (2016) Safety of Nonsteroidal Antiinflammatory Drugs. New England Journal of Medicine, 375(26): 2595-96.

World Health Organization Model List of Essential Medicines (2019), 21th edition (updated).

Ghlichloo I, Gerriets V (2020) Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). In StatPearls. Treasure Island (FL): StatPearls Publishing.

Ibraheem A, Humade S (2018) The Incidences of Use the Over Counter Drugs. Journal of Global Pharma Technology, 10(08):67-72.

Bindu S, Mazumder S, Bandyopadhyay U (2020) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Organ Damage: A Current Perspective. Biochemical Pharmacology, 180:114147.

Walker C, Biasucci LM (2018) Cardiovascular Safety of Non-Steroidal Anti-Inflammatory Drugs Revisited. Postgraduate Medicine, 130(1):55-71.

Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, et al (2019) Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs & Aging, 36(1):15-24.

Gunaydin C, Bilge SS (2018) Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level. The Eurasian Journal of Medicine, 50(2):116-121.

Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J (2018) A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging and Disease, 9(1):143-50.

Atzeni F, Masala IF, Sarzi-Puttini P (2018) A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac. Pain and Therapy, 7(2):163-77.

Bjarnason I, Scarpignato C, Holmgren E, Olszewski M, Kim D, et al (2018) Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs. Gastroenterology, 154(3):500-514.

Khan S, Andrews KL, Chin-Dusting JPF (2019) Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory? International Journal of Molecular Sciences, 20(17):4262.

Varga Z, Sabzwari SRA, Vargova V (2017) Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized Public Health Issue. Cureus, 9(4):e1144.

Bellomo RG, Carmignano SM, Palermo T, Cosenza L, Saggini A, et al. (2017) Nonsteroidal Anti-Inflammatory Drugs: Integrated Approach to Physical Medicine and Rehabilitation. Nonsteroidal Anti-Inflammatory Drugs, 67.

Hardikar MS (2008) Chiral Non-Steroidal Anti-Inflammatory Drugs - a Review. Journal of the Indian Medical Association, 106(9):615-18,622,624.

Hanna M, Moon JY (2019) A Review of Dexketoprofen Trometamol in Acute Pain. Current Medical Research and Opinion, 35(2):189-202.

Mauleón D, Artigas R, García ML, Carganico G (1996) Preclinical and Clinical Development of Dexketoprofen. Drugs, 52(5):24-45.

Barbanoj, M. J., I. Gich, R. Artigas, D. Tost, C. Moros, R. M. Antonijoan, M. L. García, and D. Mauleón. “Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers after Single and Repeated Oral Doses.” Journal of Clinical Pharmacology 38, no. S1 (1998): 33S-40S.

Barbanoj MJ, Antonijoan RM, Gich I (2001) Clinical Pharmacokinetics of Dexketoprofen. Clinical Pharmacokinetics, 40(4):245-62.

Walczak JS (2011) Analgesic Properties of Dexketoprofen Trometamol. Pain Management, 1(5):409-16.

Beltrán J, Martín-Mola E, Figueroa M, Granados J, Sanmartí R, Artigas R, et al (1998) Comparison of Dexketoprofen Trometamol and Ketoprofen in the Treatment of Osteoarthritis of the Knee. Journal of Clinical Pharmacology, 38(S1):74-80.

Marenco J.L., Pérez M, Navarro FJ, Martinez FG, Beltran J, Salvatierra D, et al (2000) A Multicentre, Randomised, Double-Blind Study to Compare the Efficacy and Tolerability of Dexketoprofen Trometamol versus Diclofenac in the Symptomatic Treatment of Knee Osteoarthritis. Clinical Drug Investigation, 19(4):247-56.

Brzeziński K, Wordliczek J (2013) Comparison of the Efficacy of Dexketoprofen and Diclofenac in Treatment of Non-Specific Low Back Pain. Annals of Agricultural and Environmental Medicine, 1:52-56.

Moore RA, McQuay HJ, Tomaszewski J, Raba G, Tutunaru D, Lietuviete N, et al (2016) Dexketoprofen/Tramadol 25 Mg/75 Mg: Randomised Double-Blind Trial in Moderate-to-Severe Acute Pain after Abdominal Hysterectomy. BMC Anesthesiology, 16(9).

Iohom G, Walsh M, Higgins G, Shorten G (2002) Effect of Perioperative Administration of Dexketoprofen on Opioid Requirements and Inflammatory Response Following Elective Hip Arthroplasty. British Journal of Anaesthesia, 88(4):520–26.

McGurk M, Robinson P, Rajayogeswaran V, De Luca M, Casini A, Artigas R, et al (1998) Clinical Comparison of Dexketoprofen Trometamol, Ketoprofen, and Placebo in Postoperative Dental Pain. Journal of Clinical Pharmacology, 38:46-54.

Rodríguez MJ, Contreras D, Gálvez R, Castro A, Camba MA, Busquets C, et al (2003) Double-Blind Evaluation of Short-Term Analgesic Efficacy of Orally Administered Dexketoprofen Trometamol and Ketorolac in Bone Cancer Pain. Pain, 104(1-2):103-10.

Sydor RI, Shevchenko T, Khranovska NM, Skachkova OV, Skivka LM (2016) The Effect of Perioperative Analgesic Drugs Omnopon and Dexketoprofen on the Functional Activity of Immune Cells in Murine Model of Tumor Surgery. The Ukrainian Biochemical Journal, 88(4):40-47.

Mainardi F, Maggioni F, Pezzola D, Zava D, Zanchin C (2014) Dexketoprofen Trometamol in the Acute Treatment of Migraine Attack: A Phase II, Randomized, Double-Blind, Crossover, Placebo-Controlled, Dose Optimization Study. The Journal of Pain: Official Journal of the American Pain Society, 15(4):388-94.

Moore RA, Barden J. (2008) Systematic Review of Dexketoprofen in Acute and Chronic Pain. BMC Clinical Pharmacology, 8:11.

Barden J, Derry S, McQuay HJ, Moore RA (2009) Single Dose Oral Ketoprofen and Dexketoprofen for Acute Postoperative Pain in Adults. The Cochrane Database of Systematic Reviews, 4: CD007355.

Gaskell H, Derry S, Wiffen PJ, Moore RA (2017) Single Dose Oral Ketoprofen or Dexketoprofen for Acute Postoperative Pain in Adults. The Cochrane Database of Systematic Reviews, 5:CD007355.

Yang B, Xu Z, Chen L, Chen X, Xie Y (2019) The Efficacy of Dexketoprofen for Migraine Attack: A Meta-Analysis of Randomized Controlled Studies. Medicine, 98(46):e17734.

Derry S, Cooper TE, Phillips T (2016) Single Fixed-Dose Oral Dexketoprofen plus Tramadol for Acute Postoperative Pain in Adults. Cochrane Database of Systematic Reviews, 9(9):CD012232.

Gabard B, Nirnberger G, Schiel H, Mascher H, Kikuta C, Mayer JM (1995) Comparison of the Bioavailability of Dexibuprofen Administered Alone or as Part of Racemic Ibuprofen. European Journal of Clinical Pharmacology, 48(6): 505-11.

Mayrhofer F (2001) Efficacy and Long-Term Safety of Dexibuprofen [S(+)-Ibuprofen]: A Short-Term Efficacy Study in Patients with Osteoarthritis of the Hip and a 1-Year Tolerability Study in Patients with Rheumatic Disorders. Clinical Rheumatology, 20(S1):22-29.

Zamani O, Böttcher E, Rieger JD, Mitterhuber J, Hawel R, Stallinger S, et al (2014) Comparison of Safety, Efficacy and Tolerability of Dexibuprofen and Ibuprofen in the Treatment of Osteoarthritis of the Hip or Knee. Wiener Klinische Wochenschrift, 126(11-12):368-75.

Hawel R, Klein G, Singer F, Mayrhofer F, Kähler ST (2003) Comparison of the Efficacy and Tolerability of Dexibuprofen and Celecoxib in the Treatment of Osteoarthritis of the Hip. Int. Journal of Clinical Pharmacology and Therapeutics, 41(4):153-64.

Yoon JS, Jeong DC, Oh JW, Lee KJ, Lee HS, Koh YY, et al (2008) The Effects and Safety of Dexibuprofen Compared with Ibuprofen in Febrile Children Caused by Upper Respiratory Tract Infection. British Journal of Clinical Pharmacology, 66(6):854-60.

Kim CK, Callaway Z, Choung JT, Yu JH, Shim KS, Kwon EM (2013) Dexibuprofen for Fever in Children with Upper Respiratory Tract Infection: Dexibuprofen for Fever in Children. Pediatrics International, 55(4):443-49.

Kollenz C, Phleps W, Kaehler ST (2009) ADIDAC Trial: Analgesia with Dexibuprofen versus Ibuprofen in Patients Suffering from Primary Dysmenorrhea: A Crossover Trial. Gynecologic and Obstetric Investigation, 67(1):25-31.

Phleps W (2001) Overview on Clinical Data of Dexibuprofen. Clinical Rheumatology, 20(S1):15-21.

Derry S, Best J, Moore RA (2013) Single Dose Oral Dexibuprofen [S(+)-Ibuprofen] for Acute Postoperative Pain in Adults. The Cochrane Database of Systematic Reviews, 10:CD007550.

Carne X, Rios J, Torres F (2009) Postmarketing Cohort Study to Assess the Safety Profile of Oral Dexketoprofen Trometamol for Mild to Moderate Acute Pain Treatment in Primary Care. Methods and Findings in Experimental and Clinical Pharmacology, 31(8):533–40.

Vellucci R (2010) The oral trometamol dexketoprofene in the treatment of mild-moderate pain. Farmaci, 9(2):1-9.

Moore RA, Barden J (2008) Systematic Review of Dexketoprofen in Acute and Chronic Pain. BMC Clinical Pharmacology, 8:11.

Laporte JR, Ibáñez L, Vidal X, Vendrell L, Leone R (2004) Upper Gastrointestinal Bleeding Associated with the Use of NSAIDs: Newer versus Older Agents. Drug Safety, 27(6):411-20.

Llorente Melero MJ, Tenías Burillo JM, Del Val Antoñana A, Zaragoza Marcet A (1999) Influence of Nonsteroidal Anti-Inflammatory Drugs on Clinical Course in Upper Gastrointestinal Tract Bleeding. Revista Espanola De Enfermedades Digestivas: Organo Oficial De La Sociedad Espanola De Patologia Digestiva, 91(7):497-507.

Kaehler ST, Phleps W, Hesse E (2003) Dexibuprofen: Pharmacology, Therapeutic Uses and Safety. InflammoPharmacology, 11(4-6):371-83.

Gómez BJ, Caunedo A, Redondo L, Esteban J, Sáenz-Dana M, Blasco M, et al (2006) Modification of Pepsinogen I Levels and Their Correlation with Gastrointestinal Injury after Administration of Dexibuprofen, Ibuprofen or Diclofenac: A Randomized, Open-Label, Controlled Clinical Trial. Int. Journal of Clinical Pharmacology and Therapeutics, 44(4):154-62.

EMA. Guideline on the investigation of bioequivalence (2010). Available from: https://www.ema.europa.eu/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf

Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry (2017) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Available from: https://www.fda.gov/media/70963/download

Garcia-Arieta A, Gordon J, Gwaza L, Mangas-Sanjuan V, Álvarez C, Torrado JJ (2015) Agitation Rate and Time for Complete Dissolution in BCS Biowaivers Based on Investigation of a BCS Biowaiver for Dexketoprofen Tablets. Molecular Pharmaceutics, 12(9):3194-3201.

Bermejo M, Kuminek G, Al-Gousous J, Ruiz-Picazo A, Tsume Y, Garcia-Arieta A, et al. (2019) Exploring Bioequivalence of Dexketoprofen Trometamol Drug Products with the Gastrointestinal Simulator (GIS) and Precipitation Pathways Analyses. Pharmaceutics, 11(3):122.

Rehnasalim, Sivakumar R, Krishnapillai, Sajeeth C, Haribabu (2013) Biowaiver monograghs of dexibuprofen. International journal of pharmaceutical, chemical and biological sciences, 3(2):424-435.

Hanif AM, Sial AA, Ali H, Zafar F, Baig MT, Bushra R, et al (2018) Dexibuprofen: Statistical Assessment of Drug Release Kinetics and Investigative Quality Perspective. Pakistan Journal of Pharmaceutical Sciences, 31(5):2157-62.

Awad H, Aboul-Enein HY, Lashin S (2012) A Validated Enantioselective HPLC Assay of Dexibuprofen in Dexibuprofen Tablet Formulations: Enantioselective HPLC Assay of Dexibuprofen. Biomedical Chromatography, 26(4):502-6.

Muralidharan S, Meyyanathan SN (2011) Development and Validation of a HPLC and an UV Spectrophotometric Methods for Determination of Dexibuprofen in Pharmaceutical Preparations. ISRN Pharmaceutics:948314.

Refbacks

  • There are currently no refbacks.


Bookmark and Share