mobiflex and lornoxicam

The aim of this study was to compare the efficacy and safety of 3 nonsteroidal anti-inflammatory drugs-intravenous tenoxicam, lornoxicam, and dexketoprofen trometamol-for the treatment of patients with renal colic.. We conducted a prospective double-blind randomized trial of consecutive adult patients who presented to the emergency department with a chief complaint of acute flank pain and had a clinical diagnosis of suspected acute renal colic. Patients were randomly allocated to receive an intravenous bolus of tenoxicam, lornoxicam, or dexketoprofen trometamol in a blinded fashion. Primary outcome measure of the study was visual analog scale (VAS) score difference at 30 minutes. Secondary outcome measures were VAS scores at 5, 15, and 120 minutes as well as rescue analgesic need at 30 minutes and adverse events during the follow-up period.. A total of 445 patients were screened, and 123 patients were enrolled in the study. The mean age was 36 ± 10 years. The mean reduction in VAS pain scores at 30 minutes was 42 ± 26 mm for tenoxicam, 57 ± 23 mm for lornoxicam, and 52 ± 25 mm for dexketoprofen (P = .047). Lornoxicam demonstrated the fastest rate of VAS score reduction over the first 30 minutes. The mean reduction values in VAS pain scores at 5, 15, and 120 minutes were similar among the 3 groups. Rescue analgesics at 30 minutes were required by 16 patients (39%) receiving tenoxicam, 10 patients (24%) receiving lornoxicam, and 8 patients (19%) receiving dexketoprofen (P = .121). No serious adverse events were observed.. Intravenous tenoxicam, lornoxicam, and dexketoprofen are all effective in the treatment of renal colic, although lornoxicam appears to reduce VAS pain scores with the fastest rate in this comparison.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Emergency Service, Hospital; Humans; Injections, Intravenous; Ketoprofen; Male; Pain Management; Pain Measurement; Piroxicam; Prospective Studies; Renal Colic; Treatment Outcome; Tromethamine

To assess the analgesic efficacy of lornoxicam and compare it with that of tenoxicam in patients undergoing extracorporeal shock-wave lithotripsy (ESWL) for renal stones.. The study was carried out in a randomized, double-blind fashion and involved 60 patients (American Society of Anesthesiologists physical status I-II) undergoing ESWL who were divided into three groups. Patients in the placebo group (n = 20) received saline and those in the lornoxicam group (n = 20) received lornoxicam 8 mg intravenously 60 min before the procedure. In the tenoxicam group, patients (n = 20) received tenoxicam 20 mg intravenously at the same time point. All patients were started on patient-controlled i.v. meperidine analgesia during the procedure. The effectiveness was assessed by using a visual analog scale (VAS) and by calculating the total analgesic consumption of meperidine during the procedure. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; nausea and vomiting, agitation, and respiratory depression were assessed.. Compared with patients in the placebo group, patients in the lornoxicam and tenoxicam groups received smaller doses of meperidine at all time points (p < 0.05). After 30, 45, and 60 min of ESWL, patients in the lornoxicam group required significantly smaller doses of meperidine than those in the tenoxicam group (p < 0.05). Patients in the placebo group showed higher VAS scores than those in the lornoxicam and tenoxicam groups at 15, 30 and 60 min. The VAS score in the lornoxicam group was lower than that in the tenoxicam group at 15, 30, and 45 min, but the difference between the groups was statistically significant only at 45 min (1 and 3, respectively; p < 0.05).. In patients undergoing ESWL the i.v. administration of a single dose of 8 mg lornoxicam provides significantly better pain control compared with tenoxicam 20 mg and placebo, without increasing adverse side-effects.

Topics: Adult; Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Injections, Intravenous; Kidney Calculi; Lithotripsy; Male; Middle Aged; Pain Measurement; Piroxicam; Treatment Outcome

The efficacy, tolerability and the morphine-sparing effects of lornoxicam were compared with those of tenoxicam when used preoperatively in patients undergoing laparoscopic cholecystectomy.. In this prospective, double-blind study, 60 ASA I-II patients undergoing laparoscopic cholecystectomy were randomized equally to receive intravenous tenoxicam 40 mg (Group T) or lornoxicam 16 mg (Group L), preemptively. Three patients withdrew from the study, so 57 patients were included in the analysis. In the postoperative period, the first morphine demand times, pain scores, side-effects and cumulative morphine consumptions were evaluated during the first 24 h.. The patient characteristics data and the duration of surgery were similar between two groups, except for body weights (P = 0.002). The first morphine demand time was significantly longer in Group L (P = 0.037), but the pain levels did not differ. The mean pain scores were higher in Group T in the 15 min (P = 0.036), 1 h (P = 0.020), 2 h (P = 0.001) and 4 h (P = 0.0042) after extubation. A statistically significant difference between two groups was found in calculated cumulative morphine consumptions per kilogram in the 15 min (P = 0.037), 30 min (P = 0.016), and 1 h (P = 0.004) and 2 h (P = 0.013) between two groups. There was no difference in the severity of nausea but 13 patients in Group T and five patients in Group L had vomiting (P = 0.018). Patient satisfaction was similar in the two groups.. Preoperatively administered lornoxicam 16 mg significantly prolonged the first morphine demand time, reduced postoperative morphine consumption during the first 4 h and caused significantly fewer adverse effects when compared with tenoxicam after laparoscopic cholecystectomy.

Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cholecystectomy, Laparoscopic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Pain Measurement; Pain, Postoperative; Piroxicam; Prospective Studies; Time Factors

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique was developed for the simultaneous determination of five non-steroidal anti-inflammatory oxicam drugs (ampiroxicam, tenoxicam, piroxicam, meloxicam and lornoxicam) in human plasma. These five oxicam drugs and isoxicam (internal standard) were extracted from human plasma with an Oasis(®) MAX cartridge column and analysed on a Unison UK-C18 column (2.0 mm × 100 mm, 3 μm) with an acetonitrile:10mM formic ammonium buffer (pH 3.0) (50:50) mobile phase at 0.20 ml/min at 37°C. The analytes were detected using a tandem mass spectrometer, equipped with an electrospray ion source (ESI). The instrument was used in multiple-reaction-monitoring (MRM) mode. The extraction yields from a 200 μl human plasma sample (containing 10 ng of each drugs) with the Oasis(®) MAX cartridge column were 93.3-102.5%. The detection limits were 0.01-6.5 ng/ml (S/N=3). Our developed method is very useful for the simultaneous determination of five oxicam (non-steroidal anti-inflammatory) drugs in human plasma by LC/MS/MS.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Forensic Toxicology; Humans; Meloxicam; Molecular Structure; Piroxicam; Tandem Mass Spectrometry; Thiazines; Thiazoles

The in vitro effects of the analgesic drugs, lornoxicam, indomethacin, tenoxicam, diclofenac sodium, ketoprofen and lincomycine, on the activity of purified human serum paraoxonase (hPON1) (EC 3.1.8.1.) were evaluated. hPON1 was purified from human serum with a final specific activity of 3840 U mg(-1) and a purity of 25.3 % using simple chromatographic methods, including DEAE-Sephadex anion exchange and Sepharose 4B-L-tyrozine-1-napthylamine hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis indicated a single protein band corresponding to hPON1. The six analgesics dose-dependently decreased in vitro hPON1 activity, with IC(50) values for lornoxicam, indomethacin, tenoxicam, diclofenac sodium, ketoprofen and lincomycine of 0.136, 0.195, 0.340, 1.639, 6.23 and 9.638 mM, respectively. K(i) constants were 0.009, 0.097, 0.306, 0.805, 13.010 and 11.116 mM, respectively. Analgesics showed different inhibition mechanisms: lornoxicam, diclofenac sodium and lincomycine were uncompetitive, indomethacin and tenoxicam were competitive, ketoprofen was noncompetitive. According to the results, inhibition potency was lornoxicam>indomethacin>tenoxicam> diclofenac sodium>ketoprofen> lincomycine.

Topics: Analgesics; Aryldialkylphosphatase; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Enzyme Inhibitors; Humans; Ketoprofen; Molecular Structure; Piroxicam; Serum

Inhibitory effects of some analgesic and anaesthetic drugs on human erythrocyte glutathione reductase were investigated. For this purpose, human erythrocyte glutathione reductase was initially purified 2139-fold in a yield of 29% by using 2', 5'-ADP Sepharose 4B affinity gel and Sephadex G-200 gel filtration chromatography. SDS polyacrylamide gel electrophoresis confirmed the purity of the enzyme by sharing a single band. A constant temperature (+4 degrees C) was maintained during the purification process. Diclofenac sodium, ketoprofen, lornoxicam, tenoxicam, etomidate, morphine and propofol exhibited inhibitory effects on the enzyme in vitro using the Beutler assay method. K(i) constants and IC(50) values for drugs were determined from Lineweaver-Burk graphs and plotting activity % versus [I] graphs, respectively. The IC(50) values of diclofenac sodium, ketoprofen, lornoxicam, propofol, tenoxicam, etomidate and morphine were 7.265, 6.278, 0.3, 0.242, 0.082, 0.0523 and 0.0128 mM and the K(i) constants were 23.97 +/- 2.1, 22.14 +/- 7.6, 0.42 +/- 0.18, 0.418 +/- 0.056, 0.13 +/- 0.025, 0.0725 +/- 0.0029 and 0.0165 +/- 0.0013 mM, respectively. While diclofenac sodium, ketoprofen, lornoxicam, tenoxicam etomidate and morphine showed competitive inhibition, propofol displayed noncompetitive inhibition.

Topics: Analgesics; Anesthetics; Chromatography, Gel; Diclofenac; Dose-Response Relationship, Drug; Erythrocytes; Etomidate; Glutathione Reductase; Humans; Inhibitory Concentration 50; Ketoprofen; Kinetics; Morphine; Piroxicam; Propofol

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK(a) values of tenoxicam in H(2)O/DMSO 1:4 (v/v) have been obtained from (1)H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 degrees C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.

Topics: Algorithms; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Meloxicam; Models, Chemical; Molecular Structure; Piroxicam; Software; Stereoisomerism; Thiazines; Thiazoles

Two sensitive and selective spectrofluorimetric and spectrophotometric stability-indicating methods have been developed for the determination of some non-steroidal anti-inflammatory oxicam derivatives namely lornoxicam (Lx), tenoxicam (Tx) and meloxicam (Mx) after their complete alkaline hydrolysis. The methods are based on derivatization of alkaline hydrolytic products with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl). The products showed an absorption maximum at 460 nm for the three studied drugs and fluorescence emission peak at 535 nm in methanol. The color was stable for at least 48 h. The optimum conditions of the reaction were investigated and it was found that the reaction proceeds quantitatively at pH 8, after heating in a boiling water bath for 30 min. The methods were found to be linear in the ranges of 1-10 microg ml(-1) for Lx and Tx and 0.5-4.0 microg ml(-1) for Mx for spectrophotometric method, while 0.05-1.0 microg ml(-1) for Lx and Tx and 0.025-0.4 microg ml(-1) for Mx for the spectrofluorimetric method. The validity of the methods was assessed according to USP guidelines. Statistical analysis of the results revealed high accuracy and good precision. The suggested procedures could be used for the determination of the above mentioned drugs in pure and dosage forms as well as in the presence of their degradation products.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Buffers; Capsules; Drug Stability; Hydrogen-Ion Concentration; Indicators and Reagents; Meloxicam; Nitrobenzenes; Oxazoles; Pharmaceutical Solutions; Piroxicam; Powders; Reproducibility of Results; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Tablets; Thiazines; Thiazoles

Intrinsic clearances (CLint-HLM-total) for the metabolism of NE-100, metoprolol, clarithromycin (CAM), lornoxicam and tenoxicam were predicted from in vitro data with recombinant cytochorme P450s (CYPs) using relative activity factor (RAF) and then compared with CLint-HLM observed in human liver microsomes (HLM). The predicted CLint-HLM-total correlated well with the observed CLint-HLM in HLM. When oral clearances (CLoral) of low-clearance drugs such as metoprolol, CAM, lornoxicam and tenoxicam were predicted from the in vitro data using four physiological models (well-stirred, parallel tube, distributed and dispersion models), the predicted CLoral corresponded well with the observed CLoralin vivo and were similar among the four models. For a high-clearance drug, the predicted CLoral of NE-100 in extensive CYP2D6 metabolizers (EMs) was substantially different between individual models, although the predicted CLoral in a poor metabolizer of CYP2D6 (PMs) was similar. The CLoral ratio of NE-100 between the EMs and the PMs predicted from the dispersion model, which leads to a reliable prediction for the high-clearance drug, was 48.4, but the ratio decreased depending on the increase of the NE-100 plasma concentration. The results suggest that the CLoral decrease in the EMs is caused by saturation of NE-100 metabolism mediated by CYP2D6 and is based on increases in plasma NE-100 concentrations dependent on the dose of NE-100. The study suggests that the RAF and the in vitro-in vivo scaling approaches are useful for predicting CLoral from in vitro data with recombinant CYPs without using HLM and hepatocytes.

Topics: Administration, Oral; Animals; Anisoles; Aryl Hydrocarbon Hydroxylases; Clarithromycin; Cytochrome P-450 Enzyme System; Dogs; Humans; Male; Metabolic Clearance Rate; Metoprolol; Models, Biological; Piroxicam; Predictive Value of Tests; Propylamines; Rats; Rats, Wistar; Recombinant Proteins

A series of thiophene [3,2-b] pyrrole derivatives were synthesized and evaluated their abilities to inhibit anti-inflammatory activity. In this series, substituent effects at the N-1, 2 and 5 positions of thiophene [3,2-b] pyrrole were examined. The results obtained are compared to those previously reported anti-inflammatory drugs like Tenidap sodium, Diclofenac sodium and Piroxicam. The results indicated the critical role of the group linked in the N-1 position and 2, 5 positions of thiophene [3,2-b] pyrrole with different functional groups.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Male; Piroxicam; Pyrroles; Rats; Rats, Wistar; Structure-Activity Relationship; Thiophenes

Hypochlorous acid (HOCl) is an oxygen-derived species involved in physiological processes related to the defence of the organism that may cause adverse effects when its production is insufficiently controlled. In order to examine its reactivity with potential scavenging molecules from the non steroidal anti-inflammatory drugs (NSAIDs) family, a competition assay based on para-aminobenzoic acid (PABA) chlorination was developed. The original optimised in vitro fluorimetric procedure offered the possibility to determine rate constants (ks) for the reaction with HOCl in physiologically relevant conditions. The specificity of the system was improved by a liquid chromatography (LC) which allows the separation of the drugs and their oxidation products. After determination of the rate constant for PABA chlorination by HOCl (mean +/- SD in M(-1) s(-1): 4.3 +/- 0.3 x 10(3)), the applied mathematical model for a chemical competition permits to obtain linear curves from competition studies between several NSAIDs and PABA. Their slopes provided the following rate constants for the different studied drugs: tenoxicam: 4.0 +/- 0.7 x 10(3), piroxicam: 3.6 +/- 0.7 x 10(3), lornoxicam: 4.3 +/- 0.7 x 10(3), meloxicam: 1.7 +/- 0.3 x 10(4), nimesulide: 2.3 +/- 0.6 x 10(2). Meloxicam therefore reacted significantly faster than the other oxicams and nimesulide, which is the weakest scavenger of the studied series. The identification of some of the oxidation products by NMR or MS permitted to explore the reaction mechanism and to examine some aspects of the structure/activity relationships for the molecules of the same chemical family.

Topics: 4-Aminobenzoic Acid; Anti-Inflammatory Agents, Non-Steroidal; Binding, Competitive; Hypochlorous Acid; Kinetics; Linear Models; Meloxicam; Molecular Structure; Oxidation-Reduction; Piroxicam; Sulfonamides; Thiazines; Thiazoles

The thermal effects of non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam, tenoxicam, piroxicam and lornoxicam have been studied in dipalmitoylphosphatidylcholine (DPPC) membrane bilayers using neutral and acidic environments (pH 2.5). The strength of the perturbing effect of the drugs is summarized to a lowering of the main phase transition temperature and a broadening of the phase transition temperature as well as broadening or abolishment of the pretransition of DPPC bilayers. The thermal profiles in the two environments were very similar. Among the NSAIDs studied meloxicam showed the least perturbing effect. The differential scanning calorimetry results (DSC) in combination with molecular modeling studies point out that NSAIDs are characterized by amphoteric interactions and are extended between the polar and hydrophobic segments of lipid bilayers. The effects of NSAIDs in membrane bilayers were also investigated using Raman spectroscopy. Meloxicam showed a gauche:trans profile similar to DPPC bilayers while the other NSAIDs increased significantly the gauche:trans ratio. In conclusion, both techniques show that in spite of the close structural similarity of the NSAIDs studied, meloxicam appears to have the lowest membrane perturbing effects probably attributed to its highest lipophilicity.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Hydrogen-Ion Concentration; Lipid Bilayers; Meloxicam; Models, Molecular; Molecular Structure; Piroxicam; Spectrum Analysis, Raman; Structure-Activity Relationship; Temperature; Thiazines; Thiazoles

CYP2C9 is involved in the metabolism of the oral anticoagulants warfarin, phenprocoumon, and acenocoumarol. It is also responsible for the 5'-hydroxylation of the nonsteroidal anti-inflammatory drug lornoxicam. Therefore, lornoxicam and the oral anticoagulants are potential inhibitors of their metabolism. Their inhibitory potency was investigated in microsomes from six human livers. An approach to predict pharmacokinetic interactions of lornoxicam from in vitro inhibition data was developed. Where possible, the forecasts were verified by comparison with data from clinical interaction studies. The following increases in steady-state plasma concentrations or areas under the plasma concentration-time curve of the oral anticoagulants by concomitant lornoxicam medication were predicted (values in parentheses are for healthy volunteers): (S)-warfarin, 1. 58-fold (1.32-fold for racemate); racemic-acenocoumarol, 1.28-fold (1.09-fold); (R)-acenocoumarol, 1.10-fold (1.0-fold); racemic-phenprocoumon, 1.11-fold (1.18-fold); and (S)-phenprocoumon, 1.13-fold (1.24-fold). Lornoxicam 5'-hydroxylation was competitively inhibited in vitro by both phenprocoumon (K(i) = 1.2 +/- 0.4 microM) and acenocoumarol (K(i) = 5.5 +/- 3.5 microM). The present results indicate that relatively close predictions of the interactions of lornoxicam with oral anticoagulants from in vitro data are possible under the assumption that hepatic lornoxicam concentrations are similar to its total plasma concentrations. The degree of pharmacokinetic interactions exhibited by oral anticoagulants and lornoxicam is dependent on the respective contribution of CYP2C9 to their total clearance.

Topics: Acenocoumarol; Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Area Under Curve; Chromatography, High Pressure Liquid; Drug Interactions; Humans; In Vitro Techniques; Microsomes, Liver; Phenprocoumon; Piroxicam; Predictive Value of Tests; Warfarin

A rapid and sensitive HPLC method for the determination of the non-steroidal anti-inflammatory drug lornoxicam in plasma samples of humans and laboratory animals is described. After addition of the internal standard (tenoxicam) the plasma sample is acidified and extracted either by dichloromethane via Extrelut columns or by solid-phase extraction using C18 columns. After evaporation of the solvent the separation is performed on a C18 column in isocratic mode with a mobile phase consisting of 0.1 M phosphate buffer (pH 6.0)-methanol and detection at 372 nm. The limit of determination was set to 10 ng/ml using 0.5 ml of sample but can be extended down to 2.0 ng/ml plasma. Using solid-phase extraction with C18 columns both lornoxicam and its main metabolite 5'-hydroxylornoxicam can be determined while extraction via Extrelut was used in studies where only lornoxicam was to be determined. This method was used successfully in several thousand samples of pharmacokinetic and bioavailability studies in animals and in humans.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Calibration; Dogs; Haplorhini; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Mice; Piroxicam; Rabbits; Rats; Solvents; Spectrophotometry, Infrared; Synovial Fluid