Piroxicam

Piroxicam is an effective and potent inhibitor of prostaglandin synthesis and a Cox-1 and Cox-2 inhibitor. Studies show that Piroxicam blocks release of platelet ADP, and inhibits Cox-1 (human prostaglandin H synthase isozyme-1, hPGHS-1) more potently than Cox-2 (hPGHS-2). Piroxicam is also a non-steroidal compound with anti-inflammatory properties.

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.[Pubmed:28358282]

Curr Med Res Opin. 2017 Jul;33(7):1255-1259.

INTRODUCTION: Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and Piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and Piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. AIM: We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. METHODS: A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm(2) area. RESULTS: All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (+/-SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The IGS after ACTX treatment was +1.9 (1.1), with a median of 2.0. A total of 86% of subjects showed a clinical improvement of IGS (>/=1) with a very significant/complete clearance (score +3 or +4) in 42% subjects. No change or a worsening of AK lesions was observed in 14% of the subjects. The product was well tolerated. No serious adverse events were reported during the duration of the trial. CONCLUSION: In this multicenter, assessor-blinded trial, the use of a film-forming medical device with sun protection and anti-inflammatory actions was effective in reducing AK lesions and improving the dermoscopy aspect of the target lesion in 86% of treated subjects. A head-to-head trial evaluating the efficacy of this medical device in comparison with diclofenac is warranted to establish whether this therapeutic approach could offer additional advantages in term of AK lesion reduction compared to an established topical treatment. (Trial ID: ISRCTN72020277).

Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines.[Pubmed:28373436]

Anticancer Res. 2017 Apr;37(4):1737-1745.

BACKGROUND/AIM: This study aimed to evaluate the in vitro efficacy of carboplatin and Piroxicam, both in isolation and combined, against T24 and 5637 human urinary bladder cancer cell lines. MATERIALS AND METHODS: Cell viability, drug interaction, cell morphology, cell proliferation, apoptosis and autophagy were analyzed after 72 h of drug exposure. Statistical analysis was performed and values of p<0.05 were considered statistically significant. RESULTS: Drug exposure in combination led to a significant reduction of cell viability comparatively to single-drug exposure. These combinations resulted in a synergistic interaction in the T24 (combination index for 50% effect (CI50)=0.65) and 5637 (CI50=0.17) cell lines. Notable increase of morphological alterations, a marked decrease of Ki-67 expression, a considerable enhancement of autophagic vacuoles and a minimal effect on apoptosis was observed in both cell lines treated with combined drugs. CONCLUSION: Data showed that in vitro combination of carboplatin and Piroxicam produced a more potent antiproliferative effect when compared to single drugs.

Effects of piroxicam on tissue distribution of sulfadimidine in West African Dwarf male and female goats.[Pubmed:28176534]

Hum Exp Toxicol. 2018 Jan;37(1):61-68.

Cases of Stevens-Johnson syndrome have been increasingly reported in Nigeria by individuals who consumed meat products of animals especially goats injected sulfonamides. Hence, tissue distribution and residues of intramuscular sulfadimidine were studied in West African Dwarf (WAD) goats. Twenty goats divided into two groups of 10 each (five males; five females) weighing 10.4 +/- 1.63 kg were administered intramuscular sulfadimidine (100 mg/kg body weight), and the second group was coadministered 5 mg/kg of Piroxicam via right and left thigh muscle, respectively. Samples of the liver, kidney, spleen, heart, lung, intestine, brain, and skeletal muscle were collected into sterile cellophane bags. Two untreated goats were killed and used for preparation of tissue standards. The tissue samples were stored frozen for analysis. High concentration of sulfadimidine residues was found in all the tissues of goats administered sulfadimidine as well as tissues of goats coadministered sulfadimidine/Piroxicam for up to 30 days postdrug administration. Generally, residues of sulfadimidine were observed to be significantly higher than the acceptable limit (0.1 ppm). Hence, consumption of meats from WAD goats administered sulfadimidine may pose very high risk of Stevens-Johnson syndrome in sensitive humans. As such consumption of such meats should be avoided.

Anti-Inflammatory Oxicams as Multi-donor Ligand Systems: pH- and Solvent-Dependent Coordination Modes of Meloxicam and Piroxicam to Ru and Os.[Pubmed:28198061]

Chemistry. 2017 Apr 6;23(20):4893-4902.

The nitrogen- and sulfur-containing 1,2-benzothiazines meloxicam and Piroxicam are widely used as nonsteroidal anti-inflammatory drugs. Intrigued by the presence of multiple donor atoms and therefore potentially rich coordination chemistry, we prepared a series of organometallic Ru and Os compounds with meloxicam and Piroxicam featuring either as mono- or bidentate ligand systems. The choice of the solvent and the pH value was identified as the critical parameter to achieve selectively mono- or bidentate coordination. The coordination modes were confirmed experimentally by NMR spectroscopy and single crystal X-ray diffraction analysis. Using DFT calculations, it was established that complexes in which meloxicam acts as a bidentate N,O donor are energetically more favorable than coordination as O,O and S,O donor systems. Since meloxicam and Piroxicam derivatives have shown anticancer activity in the past, we aimed to compare the complexes with mono- and bidentate ligands on their in vitro anticancer activity. However, stability studies revealed that only the latter complexes were stable in [D6 ]DMSO/D2 O (5:95) and therefore no direct comparisons could be made. The meloxicam complexes 1 and 2 showed moderate cytotoxicity, whereas the Piroxicam derivatives 5 and 6 were hardly active against the utilized cell lines.

Piroxicam (CP-16171) is a non-steroidal anti-inflammatory drugs, acts as a COX inhibitor, with IC50s of 47, 25 μM for human monocyte COX-1 and COX-2, respectively.

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