Journal of Korean Society for Clinical Pharmacology and Therapeutics (임상약리학회지)

Korean Society for Clinical Pharmacology and Therapeutics (대한임상약리학회)
권호 표지

A Randomized, Open Label, 2-Way Crossover Study to Assess the Pharmacokinetic Characteristics and Skin Irritation of Murupe$^{(R)}$ Patch Compared with Trast$^{(R)}$ Patch in Healthy Volunteers

건강한 자원자에서 무르페$^{(R)}$ 패치와 트라스트$^{(R)}$ 패치 투여 시 약동학적 특성 및 피부자극성을 비교 평가하기 위한 무작위배정, 공개, 2-Way 교차 임상 연구

  • Choi, Yoon Jung (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Kim, Young Mi (College of Pharmacy, Hanyang University) ;
  • Chung, Jae-Yong (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Cho, Joo-Youn (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Yu, Kyung-Sang (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Jang, In-Jin (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Lim, Kyoung Soo (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital)
  • 최윤정 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 김영미 (한양대학교 약학대학 약학과) ;
  • 정재용 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 조주연 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 유경상 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 장인진 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 임경수 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과)
  • Received : 2013.06.19
  • Accepted : 2013.06.26
  • Published : 2013.06.30
⟨ Previous Next ⟩

Abstract

Background: A piroxicam patch has been widely used to treat musculoskeletal pain. The aim of this study was to assess the pharmacokinetic (PK) characteristics and skin irritation of Murupe$^{(R)}$ patch (piroxicam 96 mg) compared with Trast$^{(R)}$ patch (piroxicam 96 mg) in healthy volunteers. Methods: A randomized, open-label, 2-way crossover study was conducted in 12 healthy Korean male subjects. They were allocated to one of the two treatment sequences of RT and TR (R, reference drug, Trast patch; T, test drug, Murupe$^{(R)}$ patch). Each patch was applied to the subject once during 48 hours. Serial blood samples were collected up to 72 hours after removing the patch and plasma concentrations were determined by high performance liquid chromatography. Safety was monitored and the skin irritation potential was assessed. Results: The plasma concentration-time profile during 48 hours showed an exponential increase in both of two patch products. Mean $C_{max}$ and $AUC_{last}$ values were not statistically different between two patch groups. Mean $AUC_{[0-48h]}$ was lower in Murupe$^{(R)}$ patch group than that in Trast$^{(R)}$ patch group; 806.4 and $1196.5ng{\cdot}h/mL$. However, the mean $AUC_{[48-120h]}$ value tended to be higher in Murupe$^{(R)}$ patch group, implying more delayed excretion than in Trast$^{(R)}$ patch group; $2724.7ng{\cdot}h/mL$ and $1989.2ng{\cdot}h/mL$. The overall results of skin irritation potential test showed no clinically significant differences between two patch groups. Conclusion: Mean $C_{max}$ and $AUC_{last}$ values in Murupe$^{(R)}$ patch group were comparable to those in Trast$^{(R)}$ patch group. Murupe$^{(R)}$ patch was safe and well tolerated in healthy male subjects.

Keywords

References

  1. Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect, 1998;47:487-504.
  2. Day RO, Brooks PM. Variations in response to non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol, 1987;23(6):655-658. https://doi.org/10.1111/j.1365-2125.1987.tb03098.x
  3. Gennaro AR. Remington's Pharmaceutical Sciences. 18th ed, Mack Publishing Company, 1990;1116.
  4. Skjodt NM, Davies NM. Clinical pharmacokinetics of lornoxicam. A short half-life oxicam. Clin Pharmacokinet, 1998;34(6):421-428. https://doi.org/10.2165/00003088-199834060-00001
  5. Bombardier C. An evidence-based evaluation of the gastrointestinal safety of coxibs. Am J Cardiol, 2002;89(6A):3D-9D.
  6. Bijlsma JW, Patient benefit risk in arthritis-a rheumatologist's perspective. Rheumatology, 2010;49:ii11-ii17. https://doi.org/10.1093/rheumatology/keq704
  7. Dahl SL, Ward JR. Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent. Pharmacotherapy, 1982;2(2):80-90. https://doi.org/10.1002/j.1875-9114.1982.tb03178.x
  8. Fourtillan JB, Girault J. Piroxicam plasma concentrations following repeated topical application of a piroxicam 0.5 % gel. Drug Invest, 1992;4(5):435-440. https://doi.org/10.1007/BF03258422
  9. EMEA, EMEA web sites on PRESS RELEASE. Key expected results, http://www. ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500012655.pdf [Online] (last visited on 5 Feb 2013).
  10. Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev, 2012;9:CD007400.
  11. Allegrini A, Nuzzo L, Pavone D, Tavella- Scaringi A, Giangreco D, Bucci M, Toniato E, Mezzetti A, Martinotti S, Comuzio S, Di Grigoli M, Bonani S. Efficacy and safety of piroxicam patch versus piroxicam cream in patients with lumbar osteoarthritis. A randomized, placebo-controlled study. Arzneimittelforschung, 2009;59(8):403-409.
  12. Campione E, Diluvio L, Paterno EJ, Chimenti S. Topical treatment of actinic keratoses with piroxicam 1 % gel: a preliminary open-label study utilizing a new clinical score. Am J Clin Dermatol, 2010;11(1):45-50. https://doi.org/10.2165/11311170-000000000-00000
  13. Dixit M, Kini AG, Kulkarni PK. Preparation and characterization of microparticles of piroxicam by spray drying and spray chilling methods. Res Pharm Sci, 2010;5(2):89-97.
  14. van Haselen RA, Fisher PA. A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee. Rheumatology (Oxford), 2000;39(7):714-719. https://doi.org/10.1093/rheumatology/39.7.714
  15. Roy SD, Gutierrez M, Flynn GL, Cleary GW. Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design. J Pharm Sci, 1996;85(5):491-495. https://doi.org/10.1021/js950415w
  16. KFDA, Korean Good Clinical Practice (KGCP), 2011.7.19 http://www.kfda.go.kr/ index.kfda?mid=95&seq=3566&cmd=v [Online] (last visited on 5 Feb 2013)
  17. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basic for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vitro bioavailability. Pharm Res, 1995;12(3):413-420. https://doi.org/10.1023/A:1016212804288
  18. Dixit M, Kulkarni PK. Lyophilization monophase solution technique for improvement of the solubility and dissolution of piroxicam. Res Pharm Sci, 2012;7(1):13-21.
  19. Lee JJ, Kim SY. Non-steroidal anti- inflammatory drug patch having improved penetration rate thereof by concentration gradient in matrix. patent registered, 10-2012-0054135 (2012)
  20. Cheong HA, Choi HK. Enhanced percutaneous absorption of piroxicam via salt formation with ethanolamines. Pharm Res. 2002;19(9):1375-1380. https://doi.org/10.1023/A:1020367212307
  21. Komatsu T, Sakurada T. Comparison of the efficacy and skin permeability of topical NSAID preparations used in Europe. Eur J Pharm Sci, 2012;47(5):890-895. https://doi.org/10.1016/j.ejps.2012.08.016
  22. Hobbs DC. Pharmacokinetics of piroxicam in man. Eur J Rheumatol Inflamm, 1983;6(1):46-55.
  23. Plessis JD, Stefaniak A, Eloff F, John S, Agner T, Chou TC, Nixon R, Steiner M, Franken A, Kudla I, Holness L. International guidelines for the in vivo assessment of skin properties in non-clinical settings: Part 2. Transepidermal water loss and skin hydration. Skin Res Technol, 2013 Jan 19. doi: 10.1111/srt.12037.