Cucurbit[7]uril-based host-guest complexes for improving bioavailability and reducing side effects of piroxicam.

Piroxicam (PX) is a nonsteroidal anti-inflammatory drug (NSAID) commonly associated with gastrointestinal (GI) injuries, including dyspepsia, heartburn, inflammation, bleeding, ulceration, and life-threatening perforation. The ß-cyclodextrin (ß-CD)-based PX formulation (PX@CD) has been shown to reduce gastric side effects by improving PX's solubility and dissolution rates. However, the solubility of PX can only be increased to a limited extent by ß-CD, due to the low binding constant between PX and ß-CD (∼100 M-1). As a result, adverse reactions such as epigastric pain and pyrosis are still commonly reported. Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic host compound that binds strongly to various drugs. In this study, we demonstrated that CB[7] forms complexes with PX in the gastric acid environment with a binding constant approximately 70 times higher than that between ß-CD and PX. The PX@CB[7] inclusion complexes exhibited rapid dissolution rates in the gastric environment. In addition, PX@CB[7] showed significantly higher oral bioavailability and maximum concentration (Cmax) compared to PX and PX@CD (1:2.5), resulting in improved anti-inflammatory effects in both mouse and rat models. Moreover, PX@CB[7] (1:2.5) had the least adhesion to the gastric mucosa and caused the mildest gastric side effects in rat models when compared to PX, PX@CD (1:2.5), and PX@CB[7] (1:1). Lastly, CB[7] demonstrated good oral biocompatibility in a subacute toxicity evaluation study. These findings indicate that CB[7] could be used as an excipient to improve treatment effectiveness and decrease adverse reactions in orally administered formulations with a favorable safety profile.

Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

Anti-inflammatory and Immunomodulatory Potency of Selenium-Enriched Probiotic Mutants in Mice with Induced Ulcerative Colitis.

Selenium-enriched Lactobacillus plantarum and Bifidobacterium longum mutants were used as a protector against Piroxicam-induced ulcerative colitis (UC). In this study, 32 BALB/c male mice were distributed to four groups: the control group, the Piroxicam group which was given 0.8 mg Piroxicam, SP and SB groups which were given 0.8 mg Piroxicam, and plus Lactobacillus plantarum and Bifidobacterium longum selenium-enriched mutants, respectively. Bodyweight; serum content of IgG, IgM, TNF-α, IL-2, IL-6, and IL-10; CBC; myeloperoxidase enzyme activity; histopathological examination of colon and spleen; and expression of TNF-α, IL-2, IL-6, and IL-10 genes in colon and spleen with qRT-PCR were determined. Bodyweight was found to reduce in the Piroxicam group and then recovery in the SB group. Serum content of IgG, IL-2, and IL-10 reduced in the Piroxicam group, whereas IgG, TNF-α, and IL-6 increased in the Piroxicam group in comparison to the other groups. Myeloperoxidase activity witnessed a significant increase in the Piroxicam group compared with the other groups. No significant differences were observed between all groups in measurements of red cells, hemoglobin, neutrophil, monocyte, eosinophil, and basophil in blood. Meanwhile, the white blood cells and platelets recorded the highest and lowest value, respectively, in the Piroxicam group. The colon of the Piroxicam group showed a noticeably massive infiltration of inflammatory cells in the lamina propria. These inflammations were mildly reduced in the SP group, while the reduction in the SB group was significant. In the Piroxicam group, splenic parenchyma saw an increase in the number of melanomacrophages, while hypertrophic plasma cells were observed in the SP group. The spleen of the SB group exhibits a nearly normal form. TNF-α and IL-6 genes had significantly upregulated in the colon of the Piroxicam group compared to the control group, while they were significantly downregulated in the SB group. In contrast, IL-2 and IL-10 genes had upregulated in the colon of the SB group compared to the control groups, while they had downregulated in the Piroxicam group. The expression of these genes had not recorded significant differences between all groups in the spleen. Therefore, this study recommends Bifidobacterium longum selenium-enriched mutants as anti-inflammatory and immunomodulatory supplements.

Nimbolide attenuates complete Freund's adjuvant induced arthritis through expression regulation of toll-like receptors signaling pathway.

Nimbolide is an active constituent of Azadirachta indica and is known for its anti-inflammatory, anti-oxidant, immune-modulatory, and anti-cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll-like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra-dermally into the sub-plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll-like receptors, IL-17, IL-23, HSP70, and IFN-γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non-steroidal anti-inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll-like receptors pathway in rheumatoid arthritis.

Analgesic Effect of Topical Piroxicam vs Phytotherapy Gel in the Treatment of Acute Soft Tissue Injuries: A Randomized Controlled Noninferiority Study.

OBJECTIVE: The study compared the efficacy and tolerability of piroxicam gel and a new topical combination of medicinal plant products (Soulagel®; Belpharma Tunisia) to treat pain caused by soft tissue injuries. METHODS: Patients (n = 1,525) were assigned to receive piroxicam gel or Soulagel. Efficacy assessments included a change of at least 50% in the pain-on-movement visual numeric scale rating from emergency department discharge (baseline) to day 7 final assessment, as well as the time required to reach pain resolution criteria, the need for rescue analgesia, patients' satisfaction, and the rate of adverse effects. RESULTS: At day 7, 1,216 patients (79.7%) achieved at least 50% reduction in visual numeric scale rating from baseline: 623 patients (82.4%) in the Soulagel group vs 593 patients (77.1%) in the piroxicam group (P = 0.01). Time to decrease pain on movement by 50% was significantly higher with piroxicam gel than with Soulagel (34 ± 1 vs 33 ± 1 days, respectively; P = 0.54). At day 7, 96.4% of patients in the Soulagel group declared being "very satisfied" to "satisfied," vs 68% in the piroxicam group (P < 0.001). There were no major adverse events in either group. CONCLUSIONS: Soulagel is not inferior to piroxicam gel for managing pain related to a soft tissue injuries. Further studies will help ascertain whether this new gel offers an alternative treatment option for this common emergency department condition.

Gastroprotective and gastric healing effects of the aqueous extract of Casearia sylvestris in rodents: Ultrasound, histological and biochemical analyzes.

ETHNOPHARMACOLOGICAL IMPORTANCE: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. AIM OF THE STUDY: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. MATERIALS AND METHODS: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1ß. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. RESULTS: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1ß, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. CONCLUSION: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.

A prospective, randomized, placebo-controlled, double-blinded clinical trial comparing the incidence and severity of gastrointestinal adverse events in dogs with cancer treated with piroxicam alone or in combination with omeprazole or famotidine.

OBJECTIVE: To assess the impact of prophylactic omeprazole and famotidine on the incidence and severity of gastrointestinal (GI) adverse events (AEs) in dogs with cancer treated with single agent piroxicam. ANIMALS: 39 dogs with a cytologic or histologic diagnosis of cancer with no history of GI disease and received piroxicam. PROCEDURES: A prospective, randomized, placebo-controlled, double-blinded clinical trial was performed. All dogs received piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h) and either omeprazole (1 mg/kg [0.45 mg/lb], PO, q 12 h), famotidine (1 mg/kg, PO, q 12 h), or placebo (lactose; PO, q 12 h). Monthly assessments of GI AEs were performed and scored by using the Veterinary Comparative Oncology Group's Common Terminology Criteria for Adverse Events (version 1.1). RESULTS: Compared with dogs in the placebo group, more dogs in the omeprazole group (84.6% vs 36.4%) and famotidine group (80.0% vs 36.4%) experienced GI AEs by day 56. The severity of GI AEs was higher in the omeprazole group, compared with the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole was not helpful in reducing the frequency or severity of GI AEs and was associated with more frequent and severer GI AEs in dogs with cancer treated with single agent piroxicam. Proton-pump inhibitors and H2-receptor antagonists should not be prescribed as prophylaxis with NSAIDs for dogs with cancer.

Effect of piroxicam administration in infertile women undergoing assisted reproductive technologies: A systematic review and meta-analysis.

OBJECTIVE: To evaluate piroxicam effect on different pregnancy outcomes among infertile women undergoing assisted reproductive technologies (ART). METHODS: We searched for the available randomized clinical trials (RCTs) in four different databases during January 2021 that compared piroxicam (intervention group) to placebo/no treatment (control group) in infertile women performing ART. We extracted the available data from included studies and pooled them in a meta-analysis model using RevMan software. We pooled the dichotomous data as risk ratios (RR) with the corresponding 95% confidence intervals (CI) using RevMan software. Our outcomes were rates of clinical pregnancy, ongoing pregnancy, miscarriage, and any adverse events. RESULTS: Seven RCTs met our inclusion criteria with a total number of 1226 patients. Piroxicam was linked to a significant increase in clinical pregnancy rate compared to control group (RR = 1.30, 95% CI [1.09, 1.55], p = .003). However, we did not report any significant difference between both groups in ongoing pregnancy rate (RR = 1.27, 95% CI [0.72, 2.24], p = .41). In addition, the rates of miscarriage and adverse events were not different among both groups. CONCLUSIONS: Piroxicam administration increases the clinical pregnancy rate among infertile women. However, piroxicam does not affect miscarriage and ongoing pregnancy rates.

Presumptive Lornoxicam Intoxication in Four Dogs.

Lornoxicam is a nonsteroidal anti-inflammatory drug extensively used in human medicine, which is not approved for canine use. Lornoxicam intoxication has been rarely reported in dogs. Four dogs of various breeds, aged 7 months to 10 years, were admitted with a recent history of melena, anorexia and depression, occurring 1-4 days after the ingestion of lornoxicam (dose range: 0.53-2.7 [median 1.17] mg/kg). No clinically relevant comorbidities were documented, but low doses of prednisolone had been given in 3 of the dogs, in close temporal association with lornoxicam. Major clinical and clinicopathologic findings on admission included mucosal pallor, melena, depression, severe anemia, neutrophilic leucocytosis, and panhypoproteinemia. Perforated pyloric and duodenal ulcers were documented in 3 dogs by exploratory celiotomy or postmortem. Prolonged hospitalization (5-20 days) with extensive supportive care and multiple blood transfusions was required in 3 of the 4 dogs who survived to discharge. Lornoxicam ingestion may cause protracted and severe gastrointestinal tract injury and bleeding, blood loss anemia, panhypoproteinemia, and perforated gastrointestinal ulcers, associated with significant morbidity and mortality in dogs.

Distinct extracellular-matrix remodeling events precede symptoms of inflammation.

Identification of early processes leading to complex tissue pathologies, such as inflammatory bowel diseases, poses a major scientific and clinical challenge that is imperative for improved diagnosis and treatment. Most studies of inflammation onset focus on cellular processes and signaling molecules, while overlooking the environment in which they take place, the continuously remodeled extracellular matrix. In this study, we used colitis models for investigating extracellular-matrix dynamics during disease onset, while treating the matrix as a complete and defined entity. Through the analysis of matrix structure, stiffness and composition, we unexpectedly revealed that even prior to the first clinical symptoms, the colon displays its own unique extracellular-matrix signature and found specific markers of clinical potential, which were also validated in human subjects. We also show that the emergence of this pre-symptomatic matrix is mediated by subclinical infiltration of immune cells bearing remodeling enzymes. Remarkably, whether the inflammation is chronic or acute, its matrix signature converges at pre-symptomatic states. We suggest that the existence of a pre-symptomatic extracellular-matrix is general and relevant to a wide range of diseases.

Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage.

OBJECTIVES: In Crohn's disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function. METHODS: We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels. RESULTS: Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice. CONCLUSIONS: GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.

Chronic Model of Inflammatory Bowel Disease in IL-10-/- Transgenic Mice: Evaluation with Ultrasound Molecular Imaging.

Objective: Acute mouse models of inflammatory bowel disease (IBD) fail to mirror the chronic nature of IBD in patients. We sought to develop a chronic mouse IBD model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI) by using dual P- and E-selectin targeted microbubbles (MBSelectin). Materials and Methods: Interleukin 10 deficient (IL-10-/- on a C57BL/6 genetic background; n=55) and FVB (n=16) mice were used. In IL-10-/-mice, various experimental regimens including piroxicam, 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS), respectively were used for promoting colitis; colitis was induced with DSS in FVB mice. Using clinical and small animal ultrasound scanners, evolution of inflammation in proximal, middle and distal colon, was monitored with USMI by using MBSelectin at multiple time points. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E staining and for P-selectin expression on immunofluorescence staining. Results: Sustained colitis was not detected with USMI in IL-10-/- or FVB mice with various experimental regimens. USMI signals either gradually decreased after the colitis enhancing/inducing drug/agents were discontinued, or the mortality rate of mice was high. Inflammation was observed on H&E staining in IL-10-/- mice with piroxicam promotion, while stable overexpression of P-selectin was not found on immunofluorescence staining in the same mice. Conclusion: Sustained colitis in IL-10-/- mice induced with piroxicam, TNBS or DSS, and in FVB mice induced with DSS, was not detected with USMI using MBSelectin, and this was verified by immunofluorescence staining for inflammation marker P-selectin. Thus, these models may not be appropriate for long-term monitoring of chronic colitis and subsequent treatment response with dual-selectin targeted USMI.

Synthesis and pharmacological evaluation of novel arylpiperazine oxicams derivatives as potent analgesics without ulcerogenicity.

Gastrotoxicity continues to be a major issue in therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Medicine is yet to develop absolutely safe analgesics. Numerous strategies are employed to discover new, safer NSAIDs, for example selective inhibition of cyclooxygenase-2, new molecular targets (e.g. microsomal prostaglandin E2 synthase-1), incorporation of cytoprotective compounds in the drug molecule or modification of the classic NSAIDs currently available on the market. The research presented in this paper is indicative of a current worldwide trend in this area of science, and is an example of the fourth strategy noted above. Two series of new arylpiperazine derivatives of the classic NSAID - piroxicam, were developed by conventional synthesis. The full range of compounds obtained proved to be between two and five times analgesically more potent than the reference drug and, most importantly, they did not show any ulcerogenic activity.

Patient-controlled intravenous analgesia with tramadol and lornoxicam after thoracotomy: A comparison with patient-controlled epidural analgesia.

To determine efficacy and safety of patient-controlled intravenous analgesia (PCIA) with tramadol and lornoxicam for postoperative analgesia, and its effects on surgical outcomes in patients following thoracotomy.The records of patients who underwent thoracotomy for lung resection between January 2014 and December 2014 at our institution were reviewed. The patients were divided into 2 groups according to postoperative pain treatment modalities. Patients of the patient-controlled epidural analgesia (PCEA) group (n = 63), received PCEA with 0.2% ropivacaine plus 0.5 µg/mL sufentanil, while patients in the PCIA group (n = 48), received PCIA with 5 mg/mL tramadol and 0.4 mg/mL lornoxicam. Data were collected for the quality of pain control, incidences of analgesia related side effects and pulmonary complications, lengths of thoracic intensive care unit stay and postoperative hospital stay, and in-hospital mortality.Pain at rest was always controlled well in both groups during the 4-day postoperative period. Patients in the PCIA group reported significantly higher pain scores on coughing and during mobilization in the first 2 postoperative days. The incidences of side effects and pulmonary complications, in-hospital mortality and other outcomes were similar between groups.PCIA with tramadol and lornoxicam can be considered as a safe and effective alternative with respect to pain control and postoperative outcomes for patients underwent thoracotomy.

Piroxicam-induced fixed drug eruption: Cross-reactivity with meloxicam.

BACKGROUND: Non-steroidal anti-inflammatory drugs constitute a main cause of fixed drug eruption (FDE). A few cases of piroxicam-induced FDE have been reported; however, the cross-reactivity among oxicams has rarely been evaluated. OBJECTIVES: To describe a series of patients with piroxicam-induced FDE, mostly confirmed by a positive patch test reaction, in whom cross-reactivity to meloxicam was assessed. METHODS: We included all cases of piroxicam-induced FDE diagnosed in the department of pharmacovigilance of Monastir. Patch tests for piroxicam and meloxicam were performed in the involved skin according to the European Network on Drug Allergy recommendations. Oral provocation tests (OPTs) were performed for patients with negative skin test results. RESULTS: Seven patients were included in this study. FDE was multiple for five patients and solitary for two. Bullous eruption was noticed in two cases. Lesional patch tests for piroxicam gave positive results in six patients. To assess cross-reactivity with meloxicam, this was patch tested. The test gave a positive result in only one patient. OPTs with meloxicam gave positive results in two patients with negative patch test results. CONCLUSION: Meloxicam is not a safe alternative for the treatment of piroxicam-induced FDE, and OPTs can be used to confirm tolerance before this drug is prescribed as a safer alternative.

Comparison of the Efficacy of Intravenous and Intramuscular Lornoxicam for the Initial Treatment of Acute Renal Colic: A Randomized Clinical Trial.

PURPOSE: We aimed to find out if there was any difference between intramuscular and intravenous administration of lornoxicam in terms of efficacy and side effects. MATERIALS AND METHODS: This study was a single-blind parallel-group randomized clinical trial. A total of 51 patients who were diagnosed with acute renal colic at our clinic were included in the study. Pain severity prior to treatment was rated using the Visual Analogue Scale (VAS). Patients were randomized into 2 groups: Group 1 (n = 27) received intramuscular 8mg lornoxicam and Group 2 (n=24) received intravenous 8mg lornoxicam. Pain severity was reassessed 30 minutes after the treatment. Pre- and post-treatment VAS scores and the mean changein the VAS scores of the 2 groups were statistically compared. RESULTS: The mean VAS scores decreased significantly from 7.65 to 2.07 in Group 1, from 7.96 to 1.38 in Group 2, and from 7.79 to 1.75 in total (P < 0.001). No statistically significant difference was observed between Groups 1 and 2 in terms of VAS score reduction (P = 0.128). None of the patients suffered any side effects except for 1 (2%) patient who had dyspepsia. CONCLUSION: Parenteral lornoxicam provides significant pain relief in patients with acute renal colic. However, no significant difference was found between intramuscular and intravenous administration in terms of analgesic efficacy.