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Much work has been focused on interactions of metal ions with nonsteroidal anti-inflammatory drugs (oxicams). Numerous attempts to synthesize several metal complexes have been published. This review highlights the synthesis and properties of the synthesized metal complexes. Different physico-chemical methods (IR, UV-Vis, measurement, thermal analysis, and NMR spectroscopy) as well as the bioactivity of the metal compounds are mentioned. [ABSTRACT FROM AUTHOR]

The formulation study of tenoxicam, a poorly water-soluble drug, was developed by use of a ternary cosolvent system and has significantly enhanced the solubility. Additionally, the relative bioavailability of testing formulation was also evaluated by New Zealand rabbit with a single i.m. injection. The three-phase diagram for dimethylsulfoxide (DMSO)/propylene glycol/water, DMSO/ethanol/water, and DMSO/polyethoxylated castor oil/ethanol system was developed. The volume ratio of 5:4:1 in the DMSO/polyethoxylated castor oil/ethanol system resulted in a more suitable vehicle than other systems, with a high solubility (20.73 mg/ml) and low viscosity (10.0 Cp). A pharmacokinetic study of bioequivalence ( F rel = 0.89) was also obtained. The present study not only provides a novel strategy improving tenoxicam solubility but also helps further scientific knowledge for the development of parenteral formulations. [ABSTRACT FROM AUTHOR]

The aim of the present study was to improve the dissolution, and therefore the bioavailability, of poorly water-soluble tenoxicam. Solid dispersions consisting of tenoxicam with two different types of polymers were prepared. The first type were PVP30 and β-cyclodextrin and the second type were two superdisintegrants, explotab and croscarmellose sodium. A solid dispersion with an explotab ratio of 1:1 (F8) had the best dissolution profile compared to all of the prepared solid dispersions as well as the pure drug, which was then formulated into tablets (T2F8). T2F8 had far better dissolution than commercial tablets, releasing only 28.3% of the drug, while T2F8 exhibited 96.5% drug release in 20 min. T2F8 was subjected to analytical validation as well as stability studies. The formulation was found to be stable after storage at 40°C for one month, 40°C and 75% relative humidity (40°C/75% RH) for one month, and 60°C for 15 days; this was confirmed by the absence of degraded product prepared in the laboratory by refluxing the drug with 1 N NaOH for 15 min. Infrared (IR) spectroscopy and differential scanning calorimetry (DSC) were performed on T2F8 to identify physicochemical interactions between the drug and carrier, hence its effect on dissolution. A simple and rapid HPLC method was also developed to determine tenoxicam in human plasma and was then used in a pharmacokinetic study. Plasma samples were analyzed on a C18 column with a mobile phase of 0.02 M sodium acetate:acetonitrile: methanol (7:2.5:0.5, v/v/v) and UV detection at 375 nm. The linear range of the plasma concentration was 1-16 μg/mL with a detection limit of 158 ng/mL. Within-day and between-day precision expressed as the relative standard deviation was less than 2%. The proposed method was successfully used in a bioequivalence study in healthy volunteers and mean pharmacokinetic parameters were calculated. [ABSTRACT FROM AUTHOR]

Abstract: We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs. *1 and *2 in AUC0–∞ (median (min–max)): 256 (230–516) vs. 150 (100–268) and 169 (124–197)μgh/mL (p <0.01) and half-life time (t1/2) 102 (79–36) vs. 56 (45–94) and 64 (60–80)h (p <0.01). Non-significant differences were observed in C max 1.9 (1.8–2.9) vs. 2.4 (1.7–3.4), 2.5 (1.6–2.9)μg/mL or in according to CYP2C8 alleles presence. CYP2C9*3 allele is associated to a longer elimination time of tenoxicam. PK parameters calculated in bioequivalence studies (AUC0–∞, t1/2) may be influenced by the presence of CYP2C9*3 allele resulting in a high variability. Thus, bioequivalence studies of tenoxicam formulations should be designed considering genotype profile. [Copyright &y& Elsevier]

Abstract: The effect of cyclodextrins on photodegradation of tenoxicam (TEN) was studied at pH 4, 7 and 10. After 60min of irradiation with UV light, the photodegradation was extensive. All cyclodextrins (α, β, or γ) stabilize TEN and reduce the rate of photodegradation. The largest effect of cyclodextrins is at pH 7. Molecular modeling results help to explain and manipulate the results. The results are discussed and compared with other results from previous studies. [Copyright &y& Elsevier]

A simple cloud-point extraction method for the determination of meloxicam in human serum was developed. Meloxicam was extracted from serum sample after adding 1 mL of 3% (v/v) Triton X-114 aqueous solution in the presence of 1M HCl and 60 mg NaCl. The meloxicam, present in the surfactant-rich phase, was enriched again with acetonitrile. Tenoxicam was used as the external standard. The separation was achieved on a C18 analytical column with a mobile phase consisting of aqueous acetic acid (1%, v/v) and acetonitrile (54:46, v/v). UV detection was performed at 360 nm. The response was linear over the range 45–2000 ng mL−1 in human serum, and intra- and interday precisions of less than 15.0% were obtained. The relative error was within ±3.0%. The recoveries of meloxicam were larger than 92.0%. The method was compared with liquid–liquid extraction. The results showed that the new method has a considerable LOQ and higher recoveries but poorer precision than liquid–liquid extraction, which exhibited poor recoveries of less than 86.0%, precisions of less than 5.0% and relative errors of less than 7.0%. The method was used for the determination of meloxicam in healthy human volunteers. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of ternary Fe(III)- (1), Co(II)- (2), Ni(II)- (3), Cu(II)- (4), Zn(II)- (5) and UO2(VI)- (6) chelates with the potent anti-inflammatory drug tenoxicam (H2ten) and (dl-alanine, Hala) are reported. All complexes are octahedral except Cu(II) and Zn(II) chelates, which are tetrahedral, and U-atoms in the uranyl chelates have a pentagonal-bipyramidal coordination sphere. The ternary Co(II) and Zn(II) complexes dissociate in dmso where orange and yellow crystals of trans,trans-[Co(II)(Hten)2(dmso)2] (8) and trans,trans-[Zn(II)(Hten)2(dmso)2] (9), respectively, were obtained. Crystallization of the binary uranyl chelate (7) from ethanol afforded the ethanol solvate cis,cis-[UO2(VI)(Hten)2(H2O)] · 2C2H5OH (7a). trans,trans-[Co(II)(Hten)2(dmso)2] (8) and trans,trans-[Zn(II)(Hten)2(dmso)2] (9) crystallize in the monoclinic space group P21/n while 7a crystallizes in the triclinic space group [image omitted]. The kinetics of the thermal decompositions for 1, 3, 4, 6 and 7 were studied and the thermodynamic parameters E*, ΔH*, ΔS* and ΔG* evaluated. [ABSTRACT FROM AUTHOR]

Objective. 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. Material and methods. 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. Results. 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). Conclusion. 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. [ABSTRACT FROM AUTHOR]

Abstract: Metal chelates of anti-inflammatory drug, tenoxicam (Ten), are synthesized and characterized using elemental analyses, IR, solid reflectance, magnetic, mass spectra, thermal analyses (TGA and DTA) and X-ray powder diffraction techniques. The chelates are found to have the general formulae [M(H2L)2(H2O) x ] (A)2·yH2O (where H2L=neutral Ten, A=Cl in case of Ni(II) and Co(II) or AcO in case of Cu(II) and Zn(II) ions, x =0–2 and y =0–2.5) and [M(H2L)3](A) z ·yH2O (A=SO4 in case of Fe(II) ion (z =1) or Cl in case of Fe(III) (z =3) and y =0–4). IR spectra reveal that Ten behaves as a neutral bidentate ligand coordinated to the metal ions through the pyridyl-N and carbonyl-O of the amide moiety. The solid reflectance spectra and magnetic moment measurements reveal that these chelates have tetrahedral, square planar and octahedral geometrical structures. Mass spectra are also used to confirm the proposed formulae and the possible fragments resulted from fragmentation of Ten and its Zn(II) and Cu(II) chelates are suggested. The thermal behaviour of the chelates (TG/DTG, DTA) are discussed in detailed manner and revealed that water molecules of crystallization together with anions are removed in the first and second steps while the Ten molecules are removed in the subsequent steps. Different thermodynamic parameters are evaluated and the relative thermal stabilities of the complexes are discussed. X-ray powder diffraction patterns are used to indicate the polymorphic form of Ten and if the complexes have molecular similarity with respect to type of coordination. [Copyright &y& Elsevier]

Introduction: In the management of bone defects, pseudoarthrosis, deformities, chronic osteomyelitis and in extremity lengthening procedures, the technique of distraction osteogenesis (DO) has been frequently used. In this experimental animal study, the effects of two non-steroidal anti-inflammatory drugs, i.e., diclofenac and tenoxicam, on the outcomes of distraction osteogenesis are investigated.Materials and Methods: In this study, 30 mature New Zealand-type male rabbits (2.5-4.5 kg) were used. The rabbits were randomized into three groups, each consisting of ten animals. Under optimal operating conditions, a pre-reconstructed circular external fixator was applied on the right tibias of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. After seven postoperative days, distraction was initiated at a rhythm of 2 x 0.5 mm/day. During the 10 days of distraction, adjunctive therapy was not instituted for group I (control group). For 10 days, group II received i.m. diclofenac sodium (0.5 mg/kg per day) and group III was treated with tenoxicam (8 mg/kg per day i.m.). At the end of 3 weeks postoperatively, five rabbits from each group were killed for histologic examinations. The remaining rabbits were killed at the end of eight postoperative weeks for biomechanical and histological analysis. Besides, radiological examinations were performed at the end of 3, 6 and 8 weeks postoperatively for the radiologic evaluation of calluses. For statistical evaluations between groups, Kruskal-Wallis variance analysis, and for intergroup assessments, Mann-Whitney test were performed.Results: For radiological evaluations, the scoring system developed by Lane and Sandhu, and for histopathological assessments, the grading system of Huddlestone et al. were used. Biomechanical tests were realized using torsional loading. During the first 3 weeks, the groups did not differ much in the radiological parameters. However, in the diclofenac group and in especially the tenoxicam group, the histological scores were lower than in the control group. Radiological images obtained at the end of 6 weeks demonstrated inadequate consolidation in the diclofenac and tenoxicam groups when compared with the control group. At the end of 8 weeks postoperatively, in consideration of biomechanical, radiological and histological tests, significantly worse regenerates were obtained in the diclofenac and tenoxicam groups.Conclusions: During the distraction osteogenesis period, diclofenac and tenoxicam affected the quality of regenerate unfavorably. This effect is sustained during all periods of bone healing. However, this finding should be supported by experimental and human studies. [ABSTRACT FROM AUTHOR]

Abstract: An extraction-less sample preparation technique followed by a RPLC-UV method on sub-two microns particles packed short column were used for the assay of tenoxicam in plasma samples. Protein precipitation was made by means of trichloroacetic acid addition. Supernatant was injected to the chromatographic column without any further pH adjustment. The mobile phase consisted in a mixture of acetonitrile and aqueous 0.1% phosphoric acid, at 2mL/min flow rate and gradient elution. The Zorbax SB-C18® column (50mm length, 4.6mm internal diameter and 1.8μm particle size) was thermostated at 60°C. The mobile phase gradient composition program allowed separation of tenoxicam and piroxicam (internal standard), column clean-up and re-equilibration within 4min. UV detection was achieved at 368±10nm. The method is characterized by a low limit of quantitation of 25ng/mL for tenoxicam, with a linearity interval up to 5500ng/mL. The use of a low volume detection cell and detector high frequency data acquisition rate produced high precision and accuracy through a whole bioequivalence study of tenoxicam in two commercially available tablet formulations, after a single oral administration dose. Full method validation is presented. The high throughput characteristic of the proposed method allowed full validation and bioanalytical study completion within a 96h period. [Copyright &y& Elsevier]

The aim of this study was to determine whether tenoxicam, administered by the intra-articular route, is useful for the treatment of osteoarthritis [OA] of the knee. Methods: Patients with knee OA were placed into three groups. Patients with no evidence of inflammation were randomized into Groups 1 and 2. Group 3 consisted of patients with knee OA with associated signs of inflammation. Groups 1 and 3 received three weekly intra-articular injections of tenoxicam, whereas only physical exercise was applied to Group 2. The Western Ontario McMaster Universities Index [WOMAC], the Lequesne Index for knee OA, and physical examination findings of the knee joint were used in the clinical and functional evaluations at baseline and months 1, 3, and 6. Results: A total of 63 subjects participated in this study. Statistically significant improvements from baseline were detected in Group 1 and Group 3, but not in Group 2. There was no lasting benefit from tenoxicam therapy since Groups 1 and 2 showed no significant differences at the six-month conclusion of the study. Similarly, Group 1 and Group 3 did not differ significantly. Conclusions: Intra-articular tenoxicam therapy seemed to show greater efficacy for pain and improvement of functional performance than exercise therapy alone, but the effects were no longer present. Tenoxicam, given intra-articularly, may provide benefit from the symptoms of OA, but the effects are transient. [ABSTRACT FROM AUTHOR]

Purpose: To compare post-operative analgesic effects of intra-articular (i.a.) drugs. Methods: After the approval of ethic committee, a randomized study on 68 patients undergoing knee arthroscopy was performed. In Group I (n = 16) 0.5 mg of neostigmine, in Group II (n = 14) 100 mg of tradamol, in Group III (n = 20) 20 mg of tenoxicam in 20 ml 0.9% NaCl solution and Group P (n = 18) 20 ml of 0.9% NaCl were injected i.a. at the end of the arthroscopy. The visual analogue scale, heart rate (HR), mean arterial pressure (MAP) values and side effects were recorded at intervals of 1, 2, 6 and 24 hours after the operation. Patient's satisfaction was also recorded. Results: The duration of analgesia in Group I was significantly longer than in the other groups. In Group III patients' satisfaction was excellent. One patient in Group I and Group II had nausea, one patient in Group II had somnolence. Conclusion: All drugs provided acceptable post-operative analgesia with excellent satisfaction in Group III. According to these results i.a. tenoxicam may be a good choice for post-operative analgesia. [ABSTRACT FROM AUTHOR]

Abstract: An overview is given of the results of organotin–NSAIDs interactions. Several organotin complexes with NSAIDs, derivatives of the carboxylic acid family and oxicam family, have been synthesized and characterized by spectroscopy and X-ray crystallography at the University of Ioannina. Results concerning the biological activity of these organotin complexes will be referred. [Copyright &y& Elsevier]

This study was designed to compare efficacy of local administration of a nonsteroidal anti-inflammatory drug with systemic administration in patients with osteoarthritis (OA) of the knee. For this purpose, intra-articular tenoxicam and oral tenoxicam therapies were applied and the improvement in control of pain and physical functioning were evaluated. A total of 69 patients with OA of the knee were randomized into three groups. Patients in the first group (41 knees of 23 patients) were treated for 1–3 weeks with once weekly intra-articular injection of tenoxicam 20 mg. Patients in the second group (45 knees of 26 patients) received 20 mg/day tenoxicam orally for 3 weeks and only physical exercises were applied to the third group (32 knees of 20 patients). Physical examination of the knee joint, Western Ontario and McMaster Universities Index and the Lequesne Algofunctional Index were used as outcome measurements at baseline, and the 1st, 3rd and 6th months. More significant improvement in pain and disability parameters was observed in groups 1 and 2 than group 3 compared with baseline measures. Among the patients’ responses a few of the differences were statistically significant, more in favour of tenoxicam, and tenoxicam seemed to be superior to exercise alone especially at the final evaluation. There was no significant difference between the oral and intra-articular tenoxicam treatment regimens. The results of this study showed that treatment of OA of the knee with intra-articular tenoxicam is as effective as that with oral tenoxicam. It can be thought that intra-articular administration can be preferred to oral therapy due to minimal possibility of systemic side effects. [ABSTRACT FROM AUTHOR]

Abstract: A rapid, sensitive and selective liquid chromatography–tandem mass spectrometric (LC–MS/MS) method for the determination of piroxicam, meloxicam and tenoxicam in human plasma was developed. Piroxicam, meloxicam, tenoxicam and isoxicam (internal standard) were extracted from human plasma with ethyl acetate at acidic pH and analyzed on a Sunfire column with the mobile phase of methanol:ammonium formate (15mM, pH 3.0) (60:40, v/v). The analytes were detected using a mass spectrometer, equipped with electrospray ion source. The instrument was set in the multiple-reaction-monitoring (MRM) mode. The standard curve was linear (r =1.000) over the concentration range of 0.50–200ng/ml. The coefficient of variation (CV) and relative error (RE) for intra- and inter-assay statistics at three QC levels were 1.0–5.4% and −5.9 to 2.8%, respectively. The recoveries of piroxicam, meloxicam and tenoxicam ranged from 78.3 to 87.1%, with that of isoxicam being 59.7%. The lower limit of quantification for piroxicam, meloxicam and tenoxicam was 0.50ng/ml using a 100μl plasma sample. This method was successfully applied to a pharmacokinetic study of piroxicam after application of transdermal piroxicam patches to humans. [Copyright &y& Elsevier]

We conducted a randomized, placebo-controlled, double blinded study to compare the analgesic effects of intraarticular neostigmine, morphine, tenoxicam, clonidine and bupivacaine in 150 patients undergoing arthroscopic knee surgery. General anaesthesia protocol was same in all patients. At the end of the surgical procedure, patients were randomized into six intraarticular groups equally. Group N received 500 mug neostigmine, Group M received 2 mg morphine, Group T received 20 mg tenoxicam, Group C received 1 microg kg(-1) clonidine, Group B received 100 mg bupivacaine and Group S received saline 20 ml. Visual analog scale scores 0, 30 and 60 min and 2, 4, 6, 12, 24, 48 and 72 h, time to first analgesic need, analgesic consumption at 48 h and 72 h and side effects were noted. Demographic and operational parameters were similar in six groups. All study groups provided analgesia when compared with saline group (P<0.05). Duration of analgesia in Group N and C was longer than other groups (P<0.001). Analgesic consumptions of Group N, C and T were lower than other groups (P<0.01). Pain scores during 2 h postoperatively were lower in all study groups than the control group (P<0.001). In Group B, median pain scores were higher than Groups N and C at 0 min and 30 min postoperatively (P<0.001). Side effects were not significantly different among the six groups. We conclude that the most effective drugs that are administered intraarticularly are neostigmine and clonidine among the five drugs we studied. Tenoxicam provided longer analgesia when compared with morphine and bupivacaine, postoperatively. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to assess the efficacy of single perioperative wound infiltration with a combination of a local anaesthetic, tramadol, and tenoxicam in patients who had undergone a caesarean delivery with spinal anaesthesia. Methods: In this randomized double blind study, patients undergoing caesarean delivery with spinal anaesthesia were treated with perioperative wound infiltration using a combination of multiple analgesic drugs. The infiltration was applied to the abdominal wall layers including visceral and parietal peritoneum, fascia, and subcutaneous tissue during the closure of the abdominal wall. Patients were randomized to receive an infiltration of 40 ml into the wound perioperatively, comprising either 0.25% bupivacaine, 100 mg tramadol, and 20 mg tenoxicam (n = 30) in Group I, or normal saline (n = 30) in Group II. Postoperative pain was assessed using a visual analogue scale (VAS). Pain and postoperative tramadol dosage were assessed at 3, 6, 12, and 24 hours after the intervention. The time passed until the first requirements for analgesia was recorded for each patient. Results: There were no differences in age, gestation time, parity or duration of surgery between groups. No subcutaneous infections or wound breakdowns occurred. The mean time before the first requirement for analgesia in Group I and Group II was 630 ± 166.6, and 300 ± 87.8 minutes, respectively, and the difference was statistically significant. The total amount of postoperative tramadol requirement in Group I and Group II was 74.3 ± 4.9 and 198.6 ± 51.9 mg, respectively; this difference was also statistically significant. VAS values were significantly higher at 3, 6, 12 and 24 hours after surgery in Group II than in Group I. Conclusion: The use of single perioperative wound infiltration with a combination of a local anaesthetic, tramadol, and tenoxicam in patients who had undergone caesarean delivery with spinal anaesthesia appears to be effective in reducing postoperative analgesic use, and would prolong analgesia time. [ABSTRACT FROM AUTHOR]

We investigated adverse events (AEs) associated with perioperative tenoxicam in a double-blind, prospective, randomised study. Patients undergoing surgery, screened for contraindications to non-steroidal anti-inflammatory drug, received tenoxicam (n=750) on 2843 days or placebo (n=251) on 988 days, in courses of 1–12 days. There was no increase in the overall incidence of side effects with tenoxicam (33 vs 38% with placebo: P=0.15), or in major side effects (3.9 vs 2.0% with placebo: P=0.11). Of major side effects possibly or probably related to tenoxicam (2.1 vs 1.2% with placebo: P=0.26), all but one involved post-operative surgical site bleeding. However, in the subgroup of patients undergoing otorhinolaryngology surgery, surgical site bleeding occurred in 18 of 171 (10.5%) patients on tenoxicam and one of 57 (1.8%) on placebo (P=0.026); of these, nine in the tenoxicam group and 0 in the placebo were classified as major (P=0.07). One patient on tenoxicam experienced endoscopically proven duodenal ulceration with malaena. In conclusion, perioperative tenoxicam is well tolerated in comparison with placebo and the incidence of drug-related major AEs (other than post-operative bleeding) is no greater than 1 in 150 in low risk patients, but in patients undergoing otorhinolaryngological surgery there may be an increased risk of post-operative bleeding. [Copyright &y& Elsevier]

A polarographic study about how three anti-inflammatories, such as Aceclofenac, Tenoxicam and Droxicam behave, using tast polarography (TP) and differential pulse polarography (DPP) was carried out. These studies were always carried out in a media formed by Methanol–Britton–Robinson aqueous buffer (0.1 M) (4:96 (v/v)) due to the low solubility of these drugs in water. A strong influence of pH on analytical signals was observed, showing that the optimal pH values were between 4 and 5. Using DPP in the optimal experimental conditions, a detection limit of 10 ppb for Tenoxicam and Droxicam and 52 ppb for Aceclofenac was reached. The DPP proposed method was successfully applied to the determination of the active compounds in commercial drugs. [Copyright &y& Elsevier]

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the modulation of the inflammatory response. However, a number of facts involving the occurrence of gastrointestinal lesions have limited the chronic use of NSAIDs. In order to diminish the occurrence of gastrointestinal damage caused by NSAIDs, the combination of NSAIDs with the H2 receptor blocker, cimetidine, has been evaluated. The anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in association with or without cimetidine were determined at pre-clinical levels. It was observed that the group of animals treated with indomethacin and cimetidine, or tenoxicam and cimetidine (10 mg/kg, p.o.) demonstrated a significant reduction (P < 0.05, ANOVA followed by Tukey– Kramer multiple comparison test) of type-III gastric ulcers. Furthermore, indomethacin or tenoxicam (10 mg/kg, p.o.) in association with cimetidine increased the anti-inflammatory activity. The group, which received indomethacin and cimetidine presented the best performance in decreasing the inflammatory process (P < 0.05, ANOVA followed by Tukey–Kramer multiple comparison test). [ABSTRACT FROM AUTHOR]

A quantitative thin-layer chromatography (TLC)–matrix-assisted laser desorption (MALDI) TOF mass spectrometry (MS) method for the determination of Piroxicam has been developed. Following preliminary experiments three different approaches to the incorporation of the internal standard (Tenoxicam) into the TLC plates were investigated. These were: (a) adding the internal standard to the mobile phase and pre-developing the plate, (b) coating the plate with internal standard by electrospraying prior to matrix application and finally, (c) mixing the internal standard into the matrix solution and electrospraying both. The most successful method was that where the internal standard was pre-developed over the plate. For this method linearity was observed over the range between 400 and 800 ng of Piroxicam. The precision was found to be in the range of 1–9% R.S.D. from the average detected value (n=5), dependent on the amount of analyte on the TLC plate. The proposed method was accurate with ±2% deviation from the known amount of Piroxicam in the sample spot. [Copyright &y& Elsevier]

Background: The aim of our study was to assess the effect of intraperitoneal and abdominal wall infiltration with bupivacaine plus tramadol and tenoxicam after total abdominal hysterectomy. Methods: Sixty patients who have undergone abdominal hysterectomy were allocated randomly to three different groups: group I (bupivacaine + tramadol): 20 patients infiltrated with 40 ml 0.25% bupivacaine plus 100 mg tramadol; group II (bupivacaine + tenoxicam): 20 patients infiltrated with 40 ml 0.25% bupivacaine plus 20 mg tenoxicam; and group III (bupivacaine + tramadol + tenoxicam): 20 patients infiltrated with 40 ml 0.25% bupivacaine + 100 mg tramadol + 20 mg tenoxicam. The intraperitoneal and abdominal wall infiltration was done to each patient after hysterectomy. The study was performed in a double-blind controlled manner. Results: In group III, pain scores (VAS) and analgesic requirement (tramadol) during the 24 h after surgery were significantly lower than in groups I and II. Tramadol requirements after the operation were similar in groups I and II. Pain scores, were similar in groups I and II. Side effects and recovery variables were similar in all groups. [ABSTRACT FROM AUTHOR]

The British Pharmacopoeia defines 2-aminopyridine (2-AP) as a potential impurity in piroxicam (PX) and tenoxicam (TX). Selective spectrofluorimetric determination of 2-AP in PX and TX, within or near the pharmacopoeial level, 0.2%, was developed, based on the measurement of the native fluorescence either in aqueous 0.1N sulfuric acid or in dioxane. Accordingly, this approach was followed for confirming purity of PX and TX in bulk and pharmaceutical preparations. The study was also extended to include simultaneous determinations of PX/2-AP and TX/2-AP systems based on selective fluorescence measurements in the cited solvents. [Copyright &y& Elsevier]

Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil°-a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the ‘clinical recovery’ of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree. [Copyright &y& Elsevier]

A speciation study was carried out in aqueous solution of the anti-inflammatory drug tenoxicam (Htenox), under quasi-physiological conditions (temperature of 37 °C and ionic strength 0.15 M NaCl) in order to determine the acidity constants from spectrophotometric studies, the pKa values found being pK1=1.143±0.008 and pK2=4.970±0.004. Subsequently, the spectrophotometrical speciation of the different complexes of Cu(II) with the drug was performed under the same conditions of temperature and ionic strength, observing the formation of Cu(Htenox)22+ with log β212=20.05±0.01, Cu(tenox)2 with log β012=13.6±0.1, Cu(Htenox)2+ with log β111=10.52±0.08, as well as Cu(tenox)+ with log β011=7.0±0.2, all of them in solution, and solid species Cu(tenox)2(s) with an estimated value of log β012(s)&ap;18.7. The crystalline structure of the complex [Cu(tenox)2(py)2]·EtOH, was also determined, and it was observed that tenoxicam employs the oxygen of the amide group and the pyridyl nitrogen to bond to the cation. [Copyright &y& Elsevier]

The reaction of tenoxicam (H2ten, 4-hydroxy-2-methyl-N-2-pyridyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide-1,1-dioxide), with M(CH3COO)2 (M=Cd, Co, Zn; 2:1 molar ratio) in hot methanol produced the microcrystalline compounds: CdII(Hten)2·2CH3OH, 1, CoII(Hten)2CH3OH3H2O, 2, ZnII(Hten)22CH3OH, 3. Single crystals of trans,trans-[CdII(Hten)2(dmso)2] 4 (dmso, dimethylsulfoxide) were obtained on cooling hot dmso solutions of 1. trans-[PtCl2(η2-C2H4)(H2ten)], 5 and trans-[PtCl2(η2-C2H4)(H2mel)]·0.5C6H6, 6·0.5C6H6 were obtained from the reaction of the Zeise's salt (K[PtCl3(η2-C2H4)]·H2O) with tenoxicam and meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxammide-1,1-dioxide), respectively (1:1 molar ratio) in ethanol solution and subsequent recrystallization from benzene. Microcrystalline FeII(Hmel)2·4H2O·2CH3OH, 7, was prepared by reacting Fe(CH3COO)2 with H2mel in refluxing methanol at a 1:2 molar ratio, under an atmosphere of ultrapure nitrogen. The X-ray diffraction structure of 4 consists of pseudo-octahedral complex molecules in which the two chelating Hten− anions (trans to each other) occupy the equatorial positions through the O-amide (Cd&z.sbnd;O(15), 2.214(2) A˚) and the N-pyridyl (Cd&z.sbnd;N(1′), 2.303(3) A˚) atoms. The conformation is ZZZ around the C(3)&z.sbnd;C(14), C(14)&z.sbnd;N(16) and N(16)&z.sbnd;C(2′) bonds. The coordination sphere is completed by two oxygen atoms from two dmso ligands at the apical positions. The sulfur atom from the thieno system as well as the SO2 function are not involved in any interactions to the metal; they contribute to the crystal packing via S⋯H&z.sbnd;C and O⋯H&z.sbnd;C hydrogen bond type interactions. The structures of 5 and 6 are similar each other as regards the coordination mode and overall conformation of the ligands (H2ten and H2mel, respectively). The platinum center links the nitrogen atom from pyridyl and thiazolyl rings with Pt&z.sbnd;N bond lengths 2.077(5) and 2.072(13) A˚, respectively. The EZE conformation of the neutral ligand molecules facilitates the formation of O(17)&z.sbnd;H⋯O(15) strong intramolecular hydrogen bonds. The (N(16))H⋯Pt intramolecular contact distances are 2.54(1) (5) and 2.93(1) A˚ (6), suggesting that an attractive interactions may exist for 5 on the basis of van der Waals radii for H and Pt. The 1H NMR data for 1 in dmso-d6 show a general shift towards higher fields for signals of Hten− ligand with respect to those of free H2ten. On the contrary the signals for H2ten and H2mel relevant to 5 and 6 (CDCl3) undergo significant low field shifts upon the coordination to the platinum center. It is worth note that the signal for the H(16) atom is moved downfield by 1.93 ppm for 5, and this can be related to the short intramolecular Pt⋯H contact distance (see above). The infrared data for 5 and 6 at the solid state show intense and sharp bands at 1524 and 1528 cm−1, respectively, attributable to the CH2&z.dbnd6;CH2 stretching vibration coupled to the CH2 bending mode, some 100 cm−1 lower energy than the band for free ethylene. [Copyright &y& Elsevier]

Oxicam group of non steroidal anti-inflammatory drugs has been chosen as a prototype molecular group that shows diverse biological functions and dynamic structural features. Photophysical studies of three drugs from this group viz., piroxicam, meloxicam and tenoxicam have been carried out in different solvents with varying polarity, H-bond character and viscosity. The spectral responses of different prototropic forms of these drugs towards varying solvent parameters have been studied, with the aim to characterize their interaction in biomimetic environment non-invasively. The nature of the lowest transition has been identified. The extinction coefficient, quantum yield and viscosity dependence on the nature of the solvents, all indicate the extreme sensitivity of these drugs to their microenvironment. [Copyright &y& Elsevier]

Tenoxicam, a thienothiazine oxicam, is a potent anti- inflammatory and antirheumatic drug. A comprehensive study on the photostability of tenoxicam is presented, including a comparison of three different methods (HPTLC/densitometry, HPLC, CE) developed for the photostability testing of the title compound. The stability indicating capability of the respective assays is proven with sample solutions forcedly degraded by artificial irradiation from a xenon source. The chromatograms and the electropherogram of the resulting solution, show tenoxicam well resolved from the degradation products. The methods are applied for testing the photostability of solutions containing tenoxicam in various concentrations (2 mg mL-1; 250 μg mL-1; 40 μg mL-1), and stored under different conditions. The stability of tenoxicam was found to be dependent on the nature of the light source, as well as on the concentration of the sample solution. The assays are validated and compared with respect to performance and precision. [ABSTRACT FROM AUTHOR]

Arthroscopic knee surgery is one of the most common surgeries done in outpatient settings; however, postoperative pain is believed to be the major barrier for discharge and early rehabilitation. In this study we evaluated and compared the efficacy of intraarticular application of long-lasting non-steroidal analgesic drug tenoxicam, a long-lasting local anaesthetic bupivacaine and combination of the two on postoperative pain after arthroscopic knee surgery. With the approval of the local ethics committee and signed informed consent of the patients, 75 American Society of Anesthesiologists I–II patients aged between 18 and 65 years going under elective arthroscopic meniscectomy were included in this randomized, blind, prospective study. The patients were divided into three groups: group-T (GT) patients (n=25) had intraarticular 20 mg of tenoxicam in 20 ml normal saline; group-B (GB) patients (n=25) had 50 mg bupivacaine in 20 ml normal saline (0.25%); group-BT (GBT) patients (n=25) had intraarticular 20 mg of tenoxicam and 50 mg bupivacaine (0.25%) in 20 ml normal saline after completion of the surgery and before deflation of the tourniquet. Postoperative analgesia was maintained by intravenous tramadol hydrochloride 50 mg/s at the first 4 h and paracetamol 500 mg and codeine 7.5 mg preparation (Pacofen) as needed (maximum six per day) during the study period. The numeric rating scale (NRS) values were at rest and at active–passive motion at 4, 12, 24 and 48 h, total analgesic consumption, at 4 h for tramadol and at the end of 48 h for oral medication; and patient satisfaction at the end of 48 h was evaluated and recorded. The demographic features of the patients, and tourniquet times, were found to be similar between the groups. Group BT had significantly lower NRS values than GB at 12 h at rest. Group BT was found to have significantly lower NRS values at 4 h compared with GT, and significantly lower NRS values at 12 h compared with GB. Group BT was found to have significantly lower NRS values at 48 h compared with GB. Group T had significantly higher NRS values at 4 h compared with GB. Group B had significantly higher values at 12 h compared with GT and GBT. Group B used significantly more analgesics than GBT and GT throughout the study period. Group BT patients had significantly more satisfaction at the end of the study period when compared with GT and GB. Application of intraarticular tenoxicam–bupivacaine solution is a simple, safe and effective method of analgesia after arthroscopic meniscectomy with high patient satisfaction. [ABSTRACT FROM AUTHOR]

This study compared the analgesic effect of intra-articular injection of tenoxicam with that of morphine on postoperative pain after anterior cruciate ligament (ACL) reconstruction. Forty-two patients undergoing arthroscopically ACL reconstructions using hamstring tendons underwent the same anesthetic protocol. The patients were randomized to receive 25 ml normal saline, 20 mg tenoxicam in 25 ml normal saline, or 2 mg morphine in 25 ml normal saline. Postoperative pain was assessed using a visual analogue scale and measuring analgesic requirements. We found both that both intra-articular tenoxicam and intra-articular morphine provided better analgesia than that in the control group. Although pain scores were similar between tenoxicam and morphine groups 30 min postoperative, the analgesic requirements in with tenoxicam were significantly lower than those with morphine group 3-6 h postoperatively. [ABSTRACT FROM AUTHOR]

The interaction of tenoxicam with six metal ions, viz. Fe(III), Bi(III), Sb(III), Cr(III), Cd(II) and Al(III) was studied using potentiometric and fluorimetric methods. In the potentiometric method the ionization constant of the ligand and stability constants of the complexes formed have been tabulated at 25±0.1 °C, ionic strength of NaNO3 in 50% (v/v) aqueous acetonitrile solution was 0.05 mol dm−3. Complexes of 1:1 and/or 1:2 and/or 1:3 metal to ligand ratios are formed. The fluorescence of tenoxicam in the presence and absence of the metal ions was studied. The drug can be determined fluorimetrically in 0.5 M HNO3 at an emission wavelength of 450 nm (excitation at 350 nm). The linear range is 0.040–0.2 μg/ml in the absence of Al(III) and 0.016–0.1 μg/ml in the presence of Al(III). Tenoxicam was determined by the proposed method in tablet, suppository and injection. The recovery percent ranged from 98.16 to 102.22%. The effect of 2-aminopyridine on the recovery of tenoxicam was also investigated. [Copyright &y& Elsevier]

The effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from saturated solutions through dorsal hairless mouse skin were investigated. Various types of vehicles, including ester-, alcohol-, and ether-types and their mixtures, were used as vehicles, and then a series of fatty acids and amines were employed as enhancers, respectively. Even though the fluxes of tenoxicam from saturated pure vehicles were generally low (0.1–1.1 μg/cm2 per h), the skin permeability of tenoxicam was significantly increased by the combination of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) or propylene glycol monocaprylate (PGMC); the highest fluxes were achieved at 40% of DGME in both of the two cosolvents. The marked synergistic enhancement was also obtained by using propylene glycol (PG)–oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. But saturated fatty acids failed to show a significant enhancing effect. The enhancement factors with the addition of oleic acid (OA) or linoleic acid (LOA) to PG were 348 and 238, respectively. Tromethamine (TM) showed an enhancing effect by the increased solubility; however, triethanolamine (TEA) did not show a significant enhancing effect. Rather, it decreased the fluxes of tenoxicam when added to PG with fatty acids. The above results indicate that the combinations of lipophilic vehicles like OA, LOA or OAl and hydrophilic vehicles like PG can be used for enhancing the skin permeation of tenoxicam. [Copyright &y& Elsevier]

Complexation of tenoxicam (TEN) with γ-, HPγ-, β-, HPβ-, and Mβ-cyclo-dextrin (CD) in aqueous solution at pH 7.4 has been investigated using phase solubility diagrams. TEN formed soluble complexes with 1:1 stoichiometry with all the CDs studied, although the inclusion stability constants (K[sub 1:1]) obtained had low values. The presence of propylene glycol (PC) in the dissolution medium decreased the stability constants and led to a higher fraction of free drug by competitive displacement and by an increase in the lipophility of the media. Among the CDs tested, MβCD was chosen for further studies since TEN-MβCD complexes yielded the best results: good solubility and the highest stability constant. The effect of MβCD and PC on the TEN partitioning coefficient was also studied in skin-buffer systems. Although each substance reduced the partitioning value, the combination of PC and MβCD increased this parameter. The noticeable increase in solubility of the drug found in the presence of MβCD allowed the formulation of carbopol gels with higher doses of TEN and a reduced amount of cosolvent. The presence of MβCD improved the percutaneous penetration of TEN through abdominal rat skin by increasing the solubility of the drug in the vehicle and by affecting the partitioning behavior of TEN in the skin. In addition, TEN retention in the skin was found to be related to the flux values attained with the corresponding gels. [ABSTRACT FROM AUTHOR]

Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1 : 1 molar ratio, were obtained by the coprecipitation method and characterized by x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The binding capacity of the CDs with TEN was also demonstrated in aqueous solution and in water-propylene glycol mixtures. The purpose of this study was to determine the effect of CDs on the in vitro percutaneous penetration of TEN from carbopol gels, taking into account the role of the CD cavity size and the nature of the substituents. The effect of pretreatment was studied too. In vitro permeation experiments were carried out on Franz diffusion cells using cellulose nitrate membranes and abdominal rat skin. In these results, the release rates of the drug scarcely decreased when the CDs were added, probably because of a lower concentration of the free drug and an increased gel viscosity. However, it was also found that CDs, particularly γ-CD and M-β-CD, can improve slightly TEN absorption through the skin. Pretreatment studies with CDs, however; provided no effects on TEN permeation, but lag time was markedly reduced suggesting a faster partitioning of TEN into the skin. Therefore, the use of pretreatment with CDs would be interesting when a quick action of the drug is desired. [ABSTRACT FROM AUTHOR]

Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group. The drug is slightly soluble in water. In a trial to increase its dissolution, different commonly used excipients were selected to prepare coprecipitates with tenoxicam. The coprecipitates were prepared using the solvent evaporation method, and the ratio used was 1:3 drug to additive. The prepared coprecipitates were subjected to a dissolution study, and they were characterized using infrared (IR) and differential scanning calorimetry (DSC) techniques. Dissolution profiles of most of the prepared coprecipitates demonstrated higher dissolution than pure tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared in the spectra of all the prepared coprecipitates except those prepared with sodium chloride, for which the IR spectrum was identical to that of the pure drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of the coprecipitates under study, indicating a change in structure from pure tenoxicam. Characterization of the coprecipitates by IR and DSC techniques revealed structural changes in the prepared coprecipitates from the plain drug, which may account for increased dissolution rates. [ABSTRACT FROM AUTHOR]

Photodegradation of tenoxicam was investigated under different reaction conditions. After 60 min of exposure to UV light, the photodegradation was extensive, and the maximum and minimum in the UV-visible spectrum were shifted to shorter and longer wavelengths, respectively. Ethanol exerted a photostabilizing effect on tenoxicam. Tenoxicam is more stable in acidic and basic media than in neutral solution. Increasing light intensity or temperature causes an increase in the rate of photodegradation. The photodegradation of tenoxicam was found to follow first-order kinetics under all these conditions. [ABSTRACT FROM AUTHOR]

SummaryThe intraoperative effects of continuous spinal anaesthesia, and the efficacy of postoperative continuous spinal analgesia in 48 elderly high risk patients undergoing major abdominal, vascular or orthopaedic surgery is reported. Intraoperative anaesthetic technique proved to be safe and provided satisfactory results in the immediate postoperative period. Furthermore, the postoperative analgesic regimen which involved intrathecal fentanyl and bupivacaine, and intravenous tenoxicam, provided effective analgesia for all patients. The intrathecal analgesic regimen was administered continuously through a PCA pump which had the facility to provide bolus doses when requested in predetermined lockout intervals. The mean doses of fentanyl and bupivacaine infused intrathecally for the first 24 h postoperatively were 14.5 ± 1.5 µg h-1 (mean ± SD) and 0.72 ± 0.08 mg h-1 (mean ± SD), respectively, while the requirements for analgesia decreased progressively over time but lasted for 118 h. The technique provided effective analgesia with low pain scores that was reflected by the ease in performing physical exercises and the pleasant co-operation with the physiotherapist. Only minor complications related to anaesthesia/analgesia were encountered. [ABSTRACT FROM AUTHOR]