Comparison of the Analgesic Effects of β-Cyclodextrin-Piroxicam, Sodium Naproxen, and Potassium Diclofenac Utilizing the Dental Pain Model

Bauduin, H; Famaey, Jean Pierre

doi:10.1300/j088v03n02_03

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…In a double-blind, randomized, crossover study on 12 healthy volunteers [119] the nociceptive threshold of the six upper front teeth (left and right central and lateral incisors, and canines) was recorded every 15 min for 4 h after a single dose of PBC 20 mg, sodium naproxen 275 mg and sodium diclofenac 50 mg. The analgesic profile was similar for the three drugs.…”

Section: Clinical Pharmacology Of Piroxicam-β-cyclodextrinmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition t...

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Section: Clinical Pharmacology Of Piroxicam-β-cyclodextrinmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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“…Previous studies show that oral diclofenac potassium tablets are effective for the acute and chronic treatment of several different pain conditions (7)(8)(9)(10)(11). In migraine, oral tablet formulations of diclofenac potassium 50 mg and 100 mg have been proven effective for acute treatment of migraine two hours following dosing (6,12).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: Results from the International Migraine Pain Assessment Clinical Trial (IMPACT)

Lipton

Grosberg

Singer³

et al. 2010

Cephalalgia

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“…1 The up-and-down procedure was adopted in 1981 and revised many times. The method involves the use of less number of animals (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), is faster, and its findings are relatively comparable to the findings from other methods. 2 Piroxicam is a benzothiazine possessing an enolic 4-hydroxy substituent, prostaglandin inhibitor, with active enterohepatic circulation resulting in prolonged half-life (30-85 hours), making it possible for single daily effective dose (20 mg).…”

Section: Introductionmentioning

confidence: 99%

“…12 Piroxicam-β-cyclodextrin has a gastrointestinal safety profile that is better than that shown by uncomplexed piroxicam. 13 It acts as a potent aquaporin-4 inhibitor and renders neuroprotection in focal cerebral ischemia in rats and therefore may be used for the treatment of brain stroke along with other anti-stroke therapeutics. 14 The reported antitumor activity of piroxicam is not considered a result of direct cytotoxicity, but at high concentration it inhibits the migration of polymorphonuclear leukocytes, decreases the production of oxygen radicals, and inhibits the function of lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

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Toxico-Neurological Effects of Piroxicam in Monogastric Animals

Saganuwan

Orinya

2016

J Exp Neurosci

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Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing use in the treatment of carcinomas in dogs and cats, there is a need for acute toxicity study of piroxicam in monogastric animals and its potential for causing secondary poisoning in puppies. Piroxicam manufactured by Shanxi Federal Pharmaceutical Co, Ltd. was used for this study. Revised up-and-down procedure was used for the estimation of median lethal dose in mouse (259.4 ± 51.9 mg/kg), rat (259.4 ± 69.6 mg/kg), rabbit (707.5 ± 130.8 mg/kg), cat (437.5 ± 128.1 mg/kg), guinea pig (218.7 ± 64.1 mg/kg), monkey (733.3 ± 83.3 mg/kg), broiler (285.3 ± 62.5 mg/kg), hen (638.3 ± 115.4 mg/kg), turkey (707.5 ± 130.8 mg/kg), pigeon (375 ± 55.9 mg/kg), and duck (311.3 ± 46.6 mg/kg). The acute toxicity signs of piroxicam at doses 207.5 mg/kg and above observed in the animals are torticollis, opisthotonos, somnolence, lethargy, diarrhea, gastroenteritis, generalized internal bleeding, anemia, congestion of the lung and liver, flaccid paralysis, cheesy lung, urinary incontinence, engorged urinary bladder, convulsive jerking of the limbs, lying in ventral recumbency, gasping for air, roaring, and death. Three out of six puppies died after being fed the carcasses of poisoned turkey, duck, and hen administered piroxicam at doses of 1000, 415, and 1000 mg/kg, respectively. White flaky cheesy materials observed in turkeys were also observed in the gastrointestinal content of the puppies. Paleness of carcasses, watery crop content, dryness of pericardium, gastroenteritis, intestinal perforation, and whitish pericardium were observed in broilers. There were effusions in thoracic and abdominal cavities as seen in all other carcasses poisoned primarily by piroxicam. Administration of atropine (0.02 mg/kg) led to survival of the remaining puppies. In conclusion, piroxicam is very to moderately toxic in monogastric animals.

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Comparison of the Analgesic Effects of β-Cyclodextrin-Piroxicam, Sodium Naproxen, and Potassium Diclofenac Utilizing the Dental Pain Model

Cited by 6 publications

References 19 publications

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: Results from the International Migraine Pain Assessment Clinical Trial (IMPACT)

Toxico-Neurological Effects of Piroxicam in Monogastric Animals

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Comparison of the Analgesic Effects of β-Cyclodextrin-Piroxicam, Sodium Naproxen, and Potassium Diclofenac Utilizing the Dental Pain Model

Cited by 6 publications

References 19 publications

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: Results from the International Migraine Pain Assessment Clinical Trial (IMPACT)

Toxico-Neurological Effects of Piroxicam in Monogastric Animals

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Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam