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Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is an effective route of drug administration, as it directs the drug to the inflamed site with reduced incidence of systemic adverse effects such as gastric hemorrhage and ulcers. Tenoxicam (TNX) is a member of NSAIDs that are marketed only as oral tablets due to very poor absorption through the skin. The current study intended to formulate and characterize a hydrogel loaded with nanostructured lipid carriers (NLCs) to enhance the transdermal delivery of TNX. Six formulations of TNX were formulated by slight modifications of high shear homogenization and ultrasonication method. The selected formula was characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo skin permeation studies. Moreover, the effectiveness of the developed formula was studied in-vivo using carrageenan-induced paw edema and hyperalgesia model in irradiated rats. Formula F4 was chosen from six formulations, as the average diameter was 679.4 ± 51.3 nm, PDI value of about 0.02, zeta potential of −4.24 mV, EE of 92.36%, globules nanoparticles without aggregations and absence of interactions in the developed formula. Additionally, the in-vivo study showed the efficacy of formula F4 (TNX-NLCs hydrogel) equivalent to oral TNX in reducing the exaggerated inflammatory response induced by carrageenan after irradiation. In conclusion, the present findings suggest that TNX-NLCs hydrogel could be a potential transdermal drug delivery system alternative to the oral formulation for the treatment of various inflammatory conditions.

The paraoxonase gene family in humans consists of three members as PON1, PON2 and PON3. PON2 can be expressed in several tissues; however, it is not released from the cells in those tissues. PON2 is also expressed in macrophages. Firstly, the commonly used NSAIDs diclofenac sodium and tenoxicam were applied on U937 cell line, the in vitro human monocyte cell line. Than PON2 specific Lactonase activity and paraoxonase family specific arylesterase were determined. Use of Diclofenac sodium in 0.845 mM dose during 6-12 h of incubation and Tenoxicam in 0.74 mM dose during 6 h of incubation resulted in a significant decline in the lactonase activity. Diclofenac sodium didn't make any change in the arylesterase activity. On the other hand, tenoxicam decreased arylesterase activity during the use of 12 h, in 0.74 mM and 1.48 mM dose.

Ibrahim Elsayed,1,2 Sinar Sayed1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates Abstract: Ocular drug delivery systems suffer from rapid drainage, intractable corneal permeation and short dosing intervals. Transcorneal drug permeation could increase the drug availability and efficiency in the aqueous humor. The aim of this study was to develop and optimize nanostructured formulations to provide accurate doses, long contact time and enhanced drug permeation. Nanovesicles were designed based on Box–Behnken model and prepared using the thin film hydration technique. The formed nanodispersions were evaluated by measuring the particle size, polydispersity index, zeta potential, entrapment efficiency and gelation temperature. The obtained desirability values were utilized to develop an optimized nanostructured in situ gel and insert. The optimized formulations were imaged by transmission and scanning electron microscopes. In addition, rheological characters, in vitro drug diffusion, ex vivo and in vivo permeation and safety of the optimized formulation were investigated. The optimized insert formulation was found to have a relatively lower viscosity, higher diffusion, ex vivo and in vivo permeation, when compared to the optimized in situ gel. So, the lyophilized nanostructured insert could be considered as a promising carrier and transporter for drugs across the cornea with high biocompatibility and effectiveness. Keywords: thin-film hydration, in situ, insert, confocal, transcorneal, tenoxicam

Two stability-indicating micellar liquid chromatographic methods were developed and validated for the determination of three oxicams, namely piroxicam (PX), tenoxicam (TX), and lornoxicam (LX), in presence of their degradation product and potential impurity (2-aminopyridine, AP). The analyses were achieved using C8 column (150 mm × 4.6 mm i.d., 5 µm particle size). In Method I, a micellar mobile phase consisting of 0.15 M SDS, 10% n-propanol, 0.3% triethylamine, and 0.02 M orthophosphoric acid (pH 3.0) was used for simultaneous determination of PX, TX, and AP. In Method II, a mobile phase of the same composition but at pH 6.0 was used for separation of LX and AP. Time-programmed UV detection was applied to allow sensitive determination of the drugs and AP. Method I showed good linearity for PX, TX, and AP over the concentration ranges of 1.0–32.0, 1.0–20.0, and 0.5–10.0 µg/mL, respectively, while Method II was linear over the concentration ranges of 0.8–32.0 and 0.5–10.0 µg/mL for LX and AP, respectively....

Tenoxicam is one of the potent non-steroidal anti-inflammatory drugs (NSAIDs), which is used clinically in the treatment of rheumatoid arthritis. Like other NSAIDs, Tenoxicam also suffers from the drawback of being associated with gastrointestinal side effects. Further, transdermal penetration of this drug is very poor, which circumvents the use of transdermal route. The main objective of this study is to exploit the concept of ultradeformable vesicles to increase the transport of Tenoxicam through transdermal route, and also to present it as a possible replacement for the oral NSAID therapy for rheumatoid arthritis. Three concentrations (5%, 15% and 25%) of three different surfactants (Tween-80, Span-80 and sodium desoxycholate) were used along with soya lecithin to prepare the ultradeformable vesicles. Among nine different types of vesicles, T3 vesicles (with 25% Tween-80) were found to have shown the smallest size (82.80 ± 0.74 nm), highest release in 24 h (98.01 ± 0.33%) and highest deformability (31....

A rapid and sensitive reversed phase high performance liquid chromatographic (HPLC) method was developed and validated for the analysis of tenoxicam in raw material and its pharmaceutical formulation. The analysis was carried out on a reversed phase C18 column, using mixtures of buffer/acetonitrile (40:60, v/v) with flow rate was of 1 mL min−1. The method was validated statistically for its linearity (correlation coefficient = 0.9983), accuracy, robustness, and intermediate precision. An experimental design was used during validation to evaluate method robustness and for the determination of intermediate precision. To test robustness, four factors were considered, mainly, percentage of organic modifier in the mobile phase, pH, flow rate, and different wavelengths. An increase of the flow rate results in a decrease of the drug concentration found, while the percentage of organic modifier, pH, and wavelength have no significant effect on the response. For intermediate precision the factors examined were mul...

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.

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.

A spectrophotometric study of the chemical coordination of two nonsteroidal anti-inflammatory drugs (tenoxicam and piroxicam) with Fe(III) has been undertaken in methanol in order to determine the stoichiometry and formation constants of the formed complexes, 1 : 1 and 1 : 2 stoichiometric ratios [Fe(III) : oxicam]. The formation constants determined with the aid of the program SQUAD, at 293 K in methanol, are: Fe(tenox), log β 11 = 4.71 ± 0.03; Fe(tenox)2, log β 12 = 8.57 ± 0.04; Fe(pirox), log β 11 = 5.54 ± 0.09; Fe(pirox)2, log β 12 = 9.75 ±0.08. However, the study in acetone gave rise to complexes with completely different stoichiometric ratios with polynuclear species [dimers of Fe(III)]. The formation constants determined with the aid of program SQUAD, at 293 K in acetone, are: Fe2(tenox), log β 21 =9.04 ± 0.03; Fe2(tenox)2, log β 22 = 14.75 ± 0.06; Fe2(tenox)3, log β 23 = 18.45 ± 0.07; Fe2(pirox), log β 21 = 9.06 ± 0.30; Fe2(pirox)2, log β 22 = 14.77 ± 0.09; Fe2(tenox)3, log β 23 = 18.48 ± 0.40. Be...

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. A...

Nonsteroidal antiinflammatory drugs (NSAIDs) are often metabolized by enzymes of the cytochrome P450 2C (CYP2C) family, CYP2C9 being the main enzyme involved in the biodisposition of these drugs. In the last decade, extensive research was conducted to identify the effect of polymorphism on the CYP2C9 gene in drug metabolism, and in the development of adverse effects after NSAIDs use. Here we review the findings obtained in these studies, with special focus on the relative importance of CYP2C9 in the metabolism and side effects of diverse NSAIDS, including aceclofenac, aspirin, celecoxib, diclofenac, dipyrone, flurbiprofen, ibuprofen, indomethacin, lornoxicam, meloxicam, naproxen, parecoxib, piroxicam, tenoxicam and valdecoxib. The role of the variant alleles CYP2C9*2, CYP2C9*3 and CYP2C8*3 in the metabolism in vivo and in vitro of these drugs is summarized, and key points that require further investigation are identified. The available information indicates that studies on these topics are still far from ...

Background : The aim of our study was to assess the efficacy of single perioperative wound infiltration with a combination of a local anesthetic, tramadol, and tenoxicam in patients who had undergone cesarean delivery with spinal anesthesia. Methods : In this randomized double blind study, patients undergoing cesarean delivery with spinal anesthesia were treated with a perioperative wound infiltration using a combination of 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 a 40 ml infiltration into the wound perioperatively of either 0.25% bupivacaine, 100 mg tramadol, and 20 mg tenoxicam (n= 30; group I) or normal saline (n= 30; group II). Postoperative pain was assessed using a visual analogue scale (VAS). The dosage of postoperative tramadol was assessed at 3, 6, 12, and 24 hours. The time until the first requirements...

In this study, we aimed to investigate the postoperative pain relief effect of preoperative tenoxicam usage in patients who undergo elective laparoscopic cholecystectomy or groin hernia repair. Eighty patients undergoing laparoscopic cholecystectomy or groin hernia repair procedures were randomized to receive either physiologic serum at 100 mL (group I, n = 40) or 20 mg iv tenoxicam (group II, n = 40) immediately before induction. Postoperative analgesic requirement, peroperative side effects and complications of drugs, operating time, post-operative mobilization time and pain score, hospitalization time, and patient pleasure were recorded. Postoperative pain was assessed by the visual analogue scale (VAS) on the recovery unit (RU), at 4, 8, and 24 h and every day at the same times in the morning. The RU median VAS score was also not different when Group 1 was compared with Group 2 (p = .97). However, the postoperative 4-h and 8-h median VAS score was significantly less (p = .01 and p = .03, respectively); first postoperative mobilization time was earlier in group 2 (p = .32). The median pain score and intramuscular analgesic requirement of patients were also reduced in Group 2 in postoperative day 1 (p = .015). The median duration of intramuscular analgesic requirement and total amount of intramuscular analgesic used in patients were also significantly less in Group 2 (p = .0001 and p = .0001, respectively). Thus, this study showed that preoperative use of iv tenoxicam is safe, simple, and effective for postoperative pain relief after laparoscopic cholecystectomy or inguinal hernia repair.

Osteoarthritis (OA) of the knee is a degenerative disorder that can cause pain and functional limitation. Intra-articular injections have become very popular in recent years. The efficacy of intraarticular tenoxicam injections in knee OA was investigated in this study. Eighty patients with knee (OA) were included in this study and were randomly assigned to two groups. Analgesics (paracetamol), hot-packs and exercise therapy were applied to both groups. Additionally, patients in Group 1 were treated with an intra-articular tenoxicam injection. Pain, functional capacity and disability parameters were evaluated. Pain was assessed by a visual analogue scale (VAS); functional capacity was assessed by Lequesne-Samson index (OA index); and the disability was evaluated by Health Assessment Quastionnaire (HAQ). After 6 months, statistically significant improvement in VAS and OA index was observed only in the tenoxicam group. Also, HAQ scores decreased significantly in Group 1.

Purpose: Patients undergoing laparoscopic procedures may experience postoperative pain. We conducted a randomized, double-blinded, placebo-controlled trial to evaluate the effectivenesses of peritoneal tramadol as an opioid analgesic, tenoxicam as an anti-imflammatory drug and bupivacaine as a local anesthetic. Methods: Patients were randomly assigned to one of four groups of 20 patients each. Group A received 50 mg tramadol (in 20 ml volume with 0.9% saline), group B received 20 mg tenoxicam (in 20 ml volume with 0.9% saline), group C received 20 ml 0.9% saline and group D received 50 mg bupivacaine HCl in 20 ml volume (10 ml 0.5% bupivacaine with 10 ml 0.9% saline) after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 30 and 60 min, and 2 and 4 h after surgery. Results: Pain intensity and analgesic requirements were significantly less in the group receiving intraperitoneal tramadol, tenoxicam and bupivacaine compared to placebo group. The pain scores of tenox...

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.

A spectrophotometric and a spectrofluorimetric methods are developed for the determination of two nonsteroidal anti-inflammatory drugs meloxicam I and tenoxicam II in the presence of their degradation products, namely 5-methyl-2-aminothiazole (III), benzothiazine carboxylic acid (IV), for meloxicam, pyridine-2-amine (V) and methyl 4-hydroxy-2-methyl-2H-thienol[2,3-e]1,2-thiazine-3-carboxylate-1, 1-dioxide (VI) for tenoxicam, Fig. 1. 10.1081/SL-120013886-F0001 Figure 1. The structure of the studied drugs and their degradation products. Both methods are based on the oxidative coupling reaction of these drugs with 3-methylbenzothiazolinone hydrazone (MBTH) hydrochloride in presence of ceric ammonium sulphate in an acid medium. Spectrophotometrically, the resulting stable coloured products showed absorption λ max at 450 nm and 465 nm for meloxicam and tenoxicam respectively. The method was applicable over the concentration range of (2–20 µg mL−1) with mean recoveries 99.90±0.85 and 100.27±1.27 respec...

Objective: This study was undertaken to assess the efficacy, acceptability and side-effects of the Norplant® (Leiras) contraceptive system during adolescence. Methods: A total of 13 adolescents were implanted with Norplant immediately after menstruation. Adolescents were advised to present for follow-up visits at 3 days after implantation, at 3, 6 and 12 months and every 1 year thereafter. Blood pressure, menstrual disorders, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose and side-effects were recorded at every visit. Results: The follow-up period was 24 months with a continuation rate of 100% (13/13) for the first 6 months, 92.5% (12/13) for 12 months and 53.8% (7/13) for the whole period. No pregnancies were observed. No infections at the implant site or expulsions were observed. Menorrhagia was observed in 4/13 (30.76%) adolescents in the third month. Thereafter all adolescents were treated with tenoxicam (prostaglandin synthetase inhibitor), so...

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 gamma-CD and M-beta-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.

In our experience, fixed drug eruption (FDE) is not a rare example of cutaneous adverse drug reactions, but the identification of the drug responsible often remains a challenge. We report on a patient in whom piroxicam was identified as the cause of recurring lesions of FDE. Epicutaneous testing with the offending drug was positive on residual lesions, but not on uninvolved skin. Histopathological and immunohistochemical findings on the positive tests were identical to those in an acute lesion of FDE. Patch testing on lesional skin revealed cross-sensitivity between piroxicam and tenoxicam, but no reactivity to thiosalicylic acid. This suggests that the molecular moiety involved in FDE to piroxicam is shared by tenoxicam, in contrast to piroxicam photosensitivity where there is no cross-reaction between these two drugs and the offending moiety is antigenically and structurally similar to thiosalicylic acid.

A simple and rapid isocratic high-performance liquid chromatographic method has been developed for the simultaneous analysis of the non-steroidal anti-inflammatory drugs tenoxicam, piroxicam, meloxicam, and lornoxicam using isoxicam as an internal standard. The analyte was chromatographed using a Lichrosphere RP18 column, a Tris acetic acid buffer-tetrabutylammonium reagent-tetrahydrofuran-acetonitrile as the mobile phase, and UV detection at 360 nm. The separation obtained was very good. The method was applied to pharmaceutical formulations containing a single active ingredient and was shown to be linear, sensible, accurate, and reproducible. A very small modification of the mobile phase enabled the separation of tenoxicam, piroxicam, isoxicam, cinnoxicam,meloxicam, and lornoxicam with symmetrical and well resolved peaks.

New simple spectrophotometric methods for the determination of piroxicam, and tenoxicam in pharmaceutical preparations based on the reaction of piroxicam, and tenoxicam with uranyl acetate have been developed. The reagent forms yellow 1:2 complexes with piroxicam and tenoxicam in alcoholic medium. The complexes are stable for more than 24 hrs. The coloured species have absorption maxima at 395 and 435 nm, with molar absorptivities of 3.8 × 103 and 0.21 × 103 1mole−1 cm−1, and the mean percentage recoveries for authentic samples were 99.11±0.79, 98.78 ± 0.62 for piroxicam and tenoxicam, respectively. The site of chelation is given, and discussed.

A size exclusion chromatography (SEC) method has been established for the study of hyaluronic acid depolymerization induced by oxygen free radicals and of the protective effect of two widely employed anti-inflammatory agents, piroxicam and tenoxicam. Molecular weight distribution of hyaluronic acid was determined by aqueous SEC equipped with absolute online detectors, light scattering detector and a viscometer. Ten min exposure of the macromolecules to a flux of hydroxyl radicals generated by xanthine/xanthine oxidase/Fe 2+ system caused massive depolymerization (Mw fell from 4.7 · 105 to 8.7 · 104). Both drugs exhibited a dose-dependent protective effect on hyaluronic acid degradation due to their radical scavenging properties. Tenoxicam was far more active than piroxicam in quenching highly reactive hydroxyl radicals (minimal effective concentrations 25 vs. 250 μM). This method gives a more complete analytical profile of the macromolecules with respect to conventional techniques.

Kirchheimer, J. C. Modulation of Receptor Bound Urokinase-type Plasminogen Activator on Human Monocytes by Non-steroidal Antiinflammatory Drugs. Scand J Rheumatol. 1993; 22: 53–57.It has been shown previously that cell surface bound fibrinolytic activitiy on human monocytes is significantly increased in patients with rheumatoid arthritis (RA) as compared to monocytes from healthy volunteers. Studies on the modulation of receptor-bound urokinase type plasminogen activator on peripheral blood monocytes of patients with RA showed that tenoxicam, a non-steroidal antiinflammatory drug with long half life and good tissue permeability, is able to downregulate the total number of urokinase receptors. Furthermore the degree of endogenous occupation of the urokinase receptor was significantly decreased in post-treatment monocytes. These data provide evidence that the non-steroidal antiinflammatory drug tenoxicam is able to downregulate cell bound fibrinolytic activity, known to contribute to pronounced degradation ...

A sensitive, specific and rapid liquid chromatographic procedure to selectively monitor tenoxicam in human plasma was developed and validated. Plasma samples were acidified and extracted using solid-phase exctration column. The procedure was linear from 0.1 to 10 μ.g/ml with a detection limit of 0.05μg/ml. The coefficient of variation for the procedure is 6.2% and 2.0% for the range of concentrations examinated. This method is suitable for pharmacological, toxicological and pharmacokinetic studies of tenoxicam.

Ten patients were recruited for this randomised double-blind pilot study to compare the efficacy and tolerance of tenoxicam 20 mg daily and piroxicam 20 mg daily in patients with rheumatoid arthritis (RA). The change in grip strength over an eight week study period was the primary efficacy variable and measurements were made using a digital pinch/grip analyser (MIE Medical Research Ltd.). There were no significant treatment differences in the change in grip strength (p greater than 0.2), although greater improvements in all efficacy parameters measured were achieved for patients receiving tenoxicam than those receiving piroxicam. Both treatments were well tolerated with few adverse events reported. Further studies with more patients are required to adequately assess whether there are any differences between treatments.

A double-blind multicentre study was conducted to compare the efficacy and safety of tenoxicam and ketoprofen in the treatment of osteoarthritis (OA). The study comprised 307 patients and the treatment period was 12 weeks. One-hundred and fifty-five patients received 20 mg tenoxicam once-daily and 152 patients received 100 mg ketoprofen b.i.d. Seventy-seven patients were prematurely withdrawn; 32 patients in the tenoxicam group and 45 in the ketoprofen group (p less than 0.05). There were only small insignificant differences in the efficacy parameters with the exception that significantly more patients in the tenoxicam group took paracetamol tablets during treatment. Adverse events developed in 29.0% of the patients on tenoxicam and in 47.3% of the patients on ketoprofen, this difference was statistically significant (p less than 0.05). The adverse events were predominantly from the gastrointestinal tract and the central nervous system. No serious side-effects occurred and the laboratory parameters showed no clinically relevant changes. The investigator's overall impression of treatment showed no significant difference between groups. Excellent or good results were judged in 55.2% of the patients on tenoxicam and in 62.1% on ketoprofen (p greater than 0.05). Tenoxicam appears to have a reasonable balance between efficacy and side-effects in the treatment of OA.

One-hundred and thirty-three clinical studies have been conducted with tenoxicam in patients with rheumatoid arthritis, osteoarthrosis, extra-articular rheumatism, ankylosing spondylitis and acute gouty arthritis. Its efficacy has been demonstrated in double-blind comparative studies against placebo, and dose-finding studies have found the optimal dose to be 20 mg. Most trials comparing tenoxicam with another NSAID have used piroxicam, an earlier oxicam derivative which also has a long half-life. In general, efficacy was similar in both drugs with a trend in favour of tenoxicam. The tolerability of tenoxicam has also been studied in detail. In short-term studies 11% of patients receiving 20 mg tenoxicam and 18% on 40 mg tenoxicam experienced side-effects (p less than 0.01), as did 20% treated with 20 mg piroxicam (p less than 0.01 against 20 mg tenoxicam). In long-term studies clinical tolerability of 20 mg tenoxicam was found to be superior to that of 20 mg piroxicam. The types of side-effects encountered were mainly gastrointestinal disturbances, followed in frequency by skin rashes. However, all side-effects were generally mild and reversible. The efficacy of tenoxicam is clearly established and its tolerability is acceptable with a 20 mg dose. Tenoxicam thus seems a promising drug and a useful addition to the therapeutic armamentarium.

The chelating tendency of the antiinflammatory drugs piroxicam and tenoxicam towards copper (II), lead (II) and cadmium (II) ions has been investigated using both differential pulse polarography and cyclic voltammetry and the stability constants of the formed complexes have been compared. The effect of the nature of the supporting electrolyte, the pH and other parameters have also been considered. Tenoxicam exhibits relatively stronger chelating properties than piroxicam towards each ion despite of their structural similarity.

The purpose of this review is to summarize what is know about the in vivo and in vitro disposition of oxicams as well as factors that may alter their metabolic profiles

The effectiveness and tolerability of tenoxicam and piroxicam, administered as a once-daily 20 mg suppository, were assessed in a comparative, randomised, double-blind trial in 48 subjects suffering from acute non-articular rheumatism. Both spontaneous and induced pain improved significantly with each of the treatments. There was no significant difference between the two treatments, whatever criterion of effectiveness was considered, i.e. spontaneous pain, induced pain or overall judgement. The incidence of undesirable side-effects was comparable for both treatments. Thirteen per cent of patients in the tenoxicam group and 16% of the patients in the piroxicam group experienced at least one undesirable side-effect. The majority of reported side-effects were of a digestive nature; however none of these were serious. The risk/benefit ratio of tenoxicam was found to be identical to that of piroxicam in the treatment of acute non-articular rheumatism.

Investigations have shown that elderly patients have an increased sensitivity to the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with a concomitant higher frequency of side-effects. Several explanations for such an observation are possible including altered receptor responsiveness or changes in absorption and disposition of a drug. From a literature survey it becomes clear that the rate and extent of NSAID absorption do not appear to be changed to a clinically significant degree in the elderly patient. Most NSAIDs are eliminated predominantly by hepatic metabolism and metabolic clearance therefore controls their elimination and accumulation upon chronic dosage. Differences in the dependence of these disposition processes on age exist between the commonly used NSAIDs. In our studies with tenoxicam, steady-state concentrations and accumulation factors did not differ in elderly subjects from those observed in a young population. Therefore, no dosage adjustment of this drug is necessary in elderly patients to achieve similar plasma concentrations following standard dosing in young subjects. Disposition processes of propionic acid derivatives seem to be more affected by advanced age as shown by reports in the literature. Alterations in plasma protein binding, with an increased free fraction of the drug subsequent to changes in serum albumin concentrations were reported with naproxen and salicylates in the aged population. Similarly, ketoprofen and ibuprofen clearance were significantly lower in the elderly than in young volunteers, and an accumulation of naproxen was reported in the elderly after multiple dosing.

Tenoxicam milk formulation is a new galenical form of a non-steroidal anti-inflammatory drug (NSAID). It is especially suitable for patients having compliance problems or difficulty in swallowing tablets. This formulation has proved to be a useful alternative oral treatment in various rheumatic conditions. Combining rapid onset of action and maintenance of active plasma levels, tenoxicam achieved good clinical efficacy and tolerability in the vast majority of the patients studied.

Every doctor faced with the task of testing a drug is well aware of the difficulty of making his or her results objective. In designing test procedures, methods need to be found which are unaffected by the subjective views of either the testing doctor or the patients undergoing the treatment. This study was designed taking this into account, using scintigraphic joint measurements in patients with chronic rheumatoid arthritis (RA) to record comparable data. Even this method, however, despite its indisputable scientific accuracy, requires clinical interpretation.

Tenoxicam is a thienothiazine derivative with marked analgesic and anti-inflammatory activities. The parenteral application of tenoxicam is especially suitable for initial therapy in acute and painful rheumatic conditions. The pharmacokinetic behaviour of tenoxicam after i.m., i.v. and p.o. administration did not differ, with the exception that higher plasma concentrations were reached during the first two hours after the parenteral dose. After both i.m. and i.v. application, tenoxicam showed a rapid onset of action, and reliable improvement of pain status. Tenoxicam was well tolerated both systemically and locally. About 10% of all patients experienced adverse events characteristic of non-steroidal anti-inflammatory drugs (NSAIDs).