lornoxicam and Inflammation

The purpose of the present study was to evaluate the effects of intravenous lornoxicam on haemodynamic and biochemical parameters, serum cytokine levels and patient outcomes in severe sepsis.. A total of 40 patients with severe sepsis were included, and were randomly assigned (20 per group) to receive either lornoxicam (8 mg administered intravenously every 12 hours for six doses) or placebo. For both groups the following were recorded: haemodynamic parameters (heart rate, mean arterial pressure), nasopharyngeal body temperature, arterial blood gas changes (pH, partial oxygen tension, partial carbon dioxide tension), plasma cytokine levels (IL-1beta, IL-2 receptor, IL-6, IL-8, tumour necrosis factor-alpha), biochemical parameters (lactate, leucocytes, trombocytes, creatinine, total bilirubin, serum glutamate oxalate transaminase), length of stay in the intensive care unit, duration of mechanical ventilation and mortality. All measurements were obtained at baseline (before the start of the study) and at 24, 48 and 72 hours from the start of lornoxicam/placebo administration.. No significant differences were found between the intravenous lornoxicam and placebo groups in major cytokines, duration of ventilation and length of intensive care unit stay, and inspired fractional oxygen/arterial oxygen tension ratio (P > 0.05).. In these patients with severe sepsis, we found intravenous lornoxicam to exert no effect on haemodynamic and biochemical parameters, cytokine levels, or patient outcomes. Because of the small number of patients included in the study and the short period of observation, these findings require confirmation by larger clinical trials of intravenous lornoxicam, administered in a dose titrated manner.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; APACHE; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Female; Hemodynamics; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Piroxicam; Placebos; Respiration, Artificial; Sepsis; Severity of Illness Index; Treatment Outcome

Increased faecal calprotectin shedding indicates gastrointestinal mucosal inflammation.. We studied the effect of short-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) on faecal calprotectin shedding in two randomized crossover studies, with treatment regimens of indomethacin or naproxen for 14 days in the first study (n = 16) and lornoxicam or naproxen for 7 days in the second study (n = 18).. The method's reproducibility and stability were satisfactory. Indomethacin and naproxen increased the faecal calprotectin significantly from a base line of 4.7 mg/l to 9.0 mg/l and 8.0 mg/l, respectively. Lornoxicam failed to increase the faecal calprotectin. Shedding after 7 days of naproxen treatment was positively correlated to gastroduodenal mucosal inflammation assessed by endoscopy.. Although seemingly influenced by concurrent upper airway infections, the study indicates that the calprotectin test may be useful for monitoring the inflammatory response to NSAID treatment, even in short-term setting.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Feces; Gastric Mucosa; Humans; Indomethacin; Inflammation; Intestinal Mucosa; Leukocyte L1 Antigen Complex; Male; Naproxen; Neural Cell Adhesion Molecules; Piroxicam; Reproducibility of Results

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3-4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of -27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62-77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.

Topics: Anti-Inflammatory Agents; Carrageenan; Drug Carriers; Humans; Inflammation; Lipids; Liposomes; Nanoparticles; Particle Size; Piroxicam; Tablets

Clinical utility of lornoxicam in oral therapy is primarily restricted by the low solubility and gastric adverse effects. This study evaluated the prospective of optimized proniosomal gel to improve the clinical efficacy of lornoxicam and compare with oral therapy.. Proniosomes were formulated by coacervation phase separation technique using span 60, lecithin and cholesterol. A four-factor three-level Box-Behnken design was used to evaluate the effect of amount of four independent variables; span 60 (X. Optimization study signifies that amount of formulation components (span 60, cholesterol, lecithin and lornoxicam) influence the vesicle size, entrapment efficiency and/or transdermal flux. Optimized formulation F19 exhibited nano size with high entrapment efficiency, adequate zeta potential, greater transdermal flux and better stability (at refrigerated conditions). The entrapment of lornoxicam in the bilayers of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F19 was distinct (p < 0.001) from gel prepared using hydroxypropyl methylcellulose (control) and displayed steady lornoxicam release by Fickian diffusion. Transdermal administration of F19 significantly inhibited the carrageenan induced hind-paw edema in rats as compared to oral lornoxicam group.. The data observed in this study demonstrated that the developed proniosomal gel (F19) improved the clinical efficacy of lornoxicam as compared to oral therapy. Graphical Abstract Proniosomal gel for transdermal delivery of lornoxicam: optimization using factorial design and in vivo evaluation in rats.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Carrageenan; Drug Compounding; Gels; Inflammation; Liposomes; Piroxicam; Rats

Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p<0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Carriers; Drug Liberation; Drug Stability; Drug Storage; Emulsions; Fatty Acids; Fatty Alcohols; Inflammation; Lipids; Male; Nanoparticles; Oleic Acid; Pain; Piroxicam; Rats; Rats, Wistar; Skin Absorption; Skin Diseases; Temperature; Time Factors

The objective of this work was to increase the solubility, in vitro skin permeability of lornoxicam from semisolid topical formulations and also to investigate the in vivo potential of nanoemulsion formulation. Optimized lornoxicam loaded nanoemulsion was prepared successfully by spontaneous self-emulsification method and the size of the stable formulations was found within the range of 102 to 200 nm. The stable nanoemulsion formulations characterized for viscosity, droplet size, transmission electron microscopy (TEM) and refractive index. In vitro permeation rate of nanoemulsion and conventional gel of lornoxicam (LX) were determined. Prmeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion NE8 and the nanogel NG8 as compared to conventional gel (LG). In vivo studies revealed a significant increase in anti-inflammatory effects as compared with conventional gel of LX. The anti-inflammatory effects of formulation NG8 showed a significant increase in percent inhibition value when compared with control, this difference was found to be highly significant (p<0.001). This work shows for the first time that lornoxicam can be formulated into nanoemulsions and may show promise in enhancing solubility and permeation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Disease Models, Animal; Edema; Emulsions; Freund's Adjuvant; Gels; Inflammation; Microscopy, Electron, Transmission; Nanomedicine; Nanoparticles; Particle Size; Permeability; Piroxicam; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility; Surface-Active Agents; Technology, Pharmaceutical; Viscosity

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effects of lornoxicam in relation to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain.. A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01-1 mg/kg), celecoxib (0.3-30 mg/kg) or loxoprofen (0.3-30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall-Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzyme-immunoassay.. In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen significantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it.. Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Celecoxib; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Extremities; Fever; Freund's Adjuvant; Hyperalgesia; Hypothalamus; Inflammation; Male; Pain Measurement; Phenylpropionates; Piroxicam; Pyrazoles; Rats; Rats, Inbred Lew; Rats, Wistar; Sulfonamides

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the analgesic properties of agents belonging to this family. As clinical pain is characterized by hyperalgesia, we evaluated the effects of NSAIDs with similar chemical structures but different selectivities for cyclo-oxygenase (COX)-1 and COX-2 in a new behavioural model of central hyperalgesia in rats. We assessed the effects of lornoxicam, piroxicam, and meloxicam on the reduction of hindpaw nociceptive thresholds to thermal stimulation produced by a 10% formaldehyde (formalin) injection into rat tail. Each drug was administered intraperitoneally (i.p.) at its ED(50)for the anti-inflammatory effect (namely the inhibition of carrageenan-induced hindpaw oedema). At this dose (1.3 mg kg(-1), 1.0 mg kg(-1), and 5.8 mg kg(-1), respectively), lornoxicam, piroxicam, and meloxicam produced the same anti-inflammatory effect, did not modify thermal nociceptive thresholds, and significantly reduced the hyperalgesia. However, only lornoxicam was fully effective for prevention of hyperalgesia. Our results indicate a dissociation between the anti-inflammatory and the anti-hyperalgesic activity of NSAIDs, where the latter seems to be more evident after the block of both COX-1 and COX-2. Finally, they suggest that our experimental model of thermal hindpaw hyperalgesia can be effectively utilized to assess the ability of different drugs to reduce central sensitization, and thus hyperalgesia.

Topics: Analgesics, Non-Narcotic; Animals; Formaldehyde; Hindlimb; Hyperalgesia; Inflammation; Male; Meloxicam; Pain Threshold; Piroxicam; Rats; Rats, Sprague-Dawley; Tail; Thiazines; Thiazoles

To evaluate the anti-inflammatory/analgesic effects of lornoxicam in the carrageenan model of inflammatory nociception.. Three hours after intraplantar carrageenan (6 mg/150 microl of saline), we assessed the effects of pre-administered lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg i.v., n=10 rats for each group) on both the peripheral oedema and number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar L4-L5 segments, in the awake rat.. Lornoxicam dose-relatedly reduced both the carrageenan evoked oedema (r=0.63 and r=0.53 for paw and ankle diameter respectively; p<0.001 for both) and total number of spinal c-Fos-LI neurons (r=0.79; p<0.001), with the strongest effect corresponding to a 75 +/- 2% reduction of the number of c-Fos-LI neurons (p<0.001) for the highest dose (9 mg/kg), and a 45 +/- 3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Reductions of both the peripheral oedema and spinal c-Fos expression were correlated (r=0.74 and r=0.57 for the paw and ankle diameter respectively; p<0.001 for both).. Our results demonstrate that lornoxicam reduces in parallel both the carrageenan-evoked oedema and spinal c-Fos expression, with clear evidence for a potent effect of low doses of lornoxicam. Correlated reductions in c-Fos expression and paw oedema suggest a predominantly peripheral site of action of lornoxicam.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cell Count; Edema; Inflammation; Male; Neurons; Nociceptors; Piroxicam; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Spinal Cord