Clinical trial on the efficacy and safety of different diclofenac formulations: Multiple-unit formulations compared to enteric coated tablets in patients with activated osteoarthritis

Schmitt, Walter; Walter, K.; Kurth, Heinz-Joerg

doi:10.1007/s10787-999-0030-z

Cited by 10 publications

(4 citation statements)

References 8 publications

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“…Of the 18 included studies, 2 studies were presented as pooled analyses from other studies, and the remaining 16 studies were individual RCT. Four studies were placebo control trials [ 21 , 23 , 24 , 29 ], and the remaining 14 studies were active control trials. Diclofenac was reported as having been found by 11 studies [ 19 – 25 , 27 , 28 , 32 , 33 ]; naproxen by 5 studies [ 17 – 19 , 26 , 30 ]; celecoxib by 4 studies [ 23 , 28 , 29 , 31 ]; ibuprofen, piroxicam, and indomethacin by only 1 study [ 16 , 19 , 24 ]; and etoricoxib by 1 study [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

Sriuttha

Sirichanchuen

Permsuwan

2018

International Journal of Hepatology

119

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Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2), and etoricoxib, which ranged from 0.005 to 0.930 (×10−2). Conclusion Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

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Section: Resultsmentioning

confidence: 99%

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

Sriuttha

Sirichanchuen

Permsuwan

2018

International Journal of Hepatology

119

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“… Summary plot of naproxen/esomeprazole magnesium versus comparators for the outcomes of ( A ) dyspepsia 37 , 44 – 47 , 49 , 50 , 53 , 58 , 60 – 62 , 64 , 69 – 78 , 80 , 81 , 83 , 84 , 86 , 88 – 119 and ( B ) any gastrointestinal event. 43 , 45 , 47 , 49 , 53 – 55 , 58 – 60 , 64 , 66 , 68 , 71 – 74 , 77 , 81 , 82 , 86 , 87 , 89 , 91 , 93 , 95 – 99 , 102 , 103 , 105 – 110 , 112 , 119 – 137 …”

Section: Figurementioning

confidence: 99%

Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses

Wolkin¹,

Datto²,

Hellmund³

et al. 2013

OARRR

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Non-steroidal anti-inflammatory drugs (NSAIDs), such as non-selective NSAIDs (nsNSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors, are commonly prescribed for arthritic pain relief in patients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS). Treatment guidelines for chronic NSAID therapy include the consideration for gastroprotection for those at risk of gastric ulcers (GUs) associated with the chronic NSAID therapy. The United States Food and Drug Administration has approved naproxen/esomeprazole magnesium tablets for the relief of signs and symptoms of OA, RA, and AS, and to decrease the risk of developing GUs in patients at risk of developing NSAID-associated GUs. The European Medical Association has approved this therapy for the symptomatic treatment of OA, RA, and AS in patients who are at risk of developing NSAID-associated GUs and/or duodenal ulcers, for whom treatment with lower doses of naproxen or other NSAIDs is not considered sufficient. Naproxen/esomeprazole magnesium tablets have been compared with naproxen and celecoxib for these indications in head-to-head trials. This systematic literature review and network meta-analyses of data from randomized controlled trials was performed to compare naproxen/esomeprazole magnesium tablets with a number of additional relevant comparators. For this study, an original review examined MEDLINE®, Embase®, and the Cochrane Controlled Trials Register from database start to April 14, 2009. Using the same methodology, a review update was conducted to December 21, 2009. The systematic review and network analyses showed naproxen/esomeprazole magnesium tablets have an improved upper gastrointestinal tolerability profile (dyspepsia and gastric or gastroduodenal ulcers) over several active comparators (naproxen, ibuprofen, diclofenac, ketoprofen, etoricoxib, and fixed-dose diclofenac sodium plus misoprostol), and are equally effective as all active comparators in treating arthritic symptoms in patients with OA, RA, and AS. Naproxen/esomeprazole magnesium tablets are therefore a valuable option for treating arthritic symptoms in eligible patients with OA, RA, and AS.

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“…Bei einem festgestellten Bioverfügbarkeitsunterschied von über 40 % kann allerdings nicht ausgeschlossen werden, daß diese Unterschiede auch klinische Bedeutung haben können. Dies ist vor allem vor dem Hintergrund zu sehen, daß auch bei der Behandlung von Arthritiden mit Diclofenac initial hohe Plasmaspiegel zu einer signifikant besseren Wirkung führen [10].…”

Section: Diskussionunclassified

Relative Bioverfügbarkeit von Diclofenac nach Einmalgabe einer neuen Multiple-Unit-Formulierung mit magensaftresistent befilmten Pellets

Walter¹,

Nieciecki²

2011

Arzneimittelforschung

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The relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after a single administration of a multiple-unit formulation containing 75 mg diclofenac sodium in enteric-coated pellets (A) in comparison to an enteric-coated tablet with 50 mg diclofenac sodium (B), a capsule containing 140 mg diclofenac resinate (C) and a dispersible tablet containing 46.5 mg diclofenac acid (D). The study was carried out in a four-way crossover design in 16 healthy male volunteers. Serum concentrations of diclofenac were determined with a validated and specific HPLC-method. After dose normalisation, a mean relative bioavailability of 99% (B), 142% (C) and 116% (D) was determined for the pellet formulation. According to the corresponding 90%-confidence interval, bioequivalence for the extent of bioavailability of the test formulation can be concluded compared to the enteric-coated tablet. In comparison to the formulations C and D, the test formulation showed an increased extent of bioavailability. Further differences in pharmacokinetics were observed for the rate-dependent parameters. For the test formulation, the highest mean maximum serum concentration (1595 ng/ml) was measured with a corresponding tmax of 0.8 h. For the reference formulations, mean peak serum concentrations of 1285 ng/ml after 2.0 h (B), 370 ng/ml after 1.8 h (C) and 735 ng/ml after 1.9 h (D) were observed. Despite the enteric-coating of the pellets, a short lagtime of 0.4 h was determined for the test formulation. For the other rapid-release formulation (D), the lagtime was of a similar magnitude (0.3 h), while drug release and absorption from the enteric-coated tablet and the diclofenac resinate capsule were delayed (1.8 and 0.7 h, respectively). Due to the rapid and high bioavailability of diclofenac, the multiple-unit formulation fulfills the prerequisites for the oral treatment of acute painful conditions when prompt analgesic and anti-inflammatory efficacy is desired.

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Clinical trial on the efficacy and safety of different diclofenac formulations: Multiple-unit formulations compared to enteric coated tablets in patients with activated osteoarthritis

Cited by 10 publications

References 8 publications

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses

Relative Bioverfügbarkeit von Diclofenac nach Einmalgabe einer neuen Multiple-Unit-Formulierung mit magensaftresistent befilmten Pellets

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