Preparation and thermal study of Mg-diclofenac compound in solid state

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Tissue tolerance of diclofenac sodium encapsulated in liposomes after intramuscular administration

In this work the effect of the encapsulation of diclofenac sodium within liposomes on the reduction of the myotoxicity after intramuscular administration in rats was studied. Diclofenac sodium was encapsulated in small unilamellar liposomes obtained from phosphatidylcholine, cholesterol, and a-tocopherol (40:10:0.04 mM), and administered by intramuscular injection in the quadriceps femoral muscle of male Wistar rats. After a single dose of 0.2 mg diclofenac formulations the local tissue damage was assessed by plasma creatine kinase (CPK) activity and histological analysis. It was demonstrated that formulations containing free diclofenac produced a higher increase in CPK activity, while those encapsulated in liposomes exhibited CPK activity similar to the control groups. Histopathological analysis of local muscle tissue performed on the third and seventh days following the injection showed intense cellular damage when free drug solution was used, while encapsulation in liposome protected the tissue against the local tissue inflammation.

Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication

AIM OF STUDY: To report the management of cardiovascular failure refractory to standard catecholamine therapy with terlipressin in a patient with tricyclic antidepressant (TCA) intoxication. CASE REPORT: A 41-year-old woman, with suicidal ingestion of 11.25 g amitriptyline and 1500 mg diclofenac, was admitted to the emergency department. After 30 min in ventricular fibrillation, with ongoing CPR, she regained a potentially perfusing rhythm, but with hypotension refractory to standard catecholamine therapy with adrenaline, 2 microg/kg/min (norepinephrine); adrenaline, 1 microg/kg/min (epinephrine) until 55 min after admission. An injection of 1 mg terlipressin restored mean arterial blood pressure >65 mmHg within 10 min. Ten hours after admission to the intensive care unit, catecholamine support could be withdrawn because of a stable haemodynamic state. Within 7 days, all organ function recovered, and the patient regained full neurological function. CONCLUSIONS: Successful management of cardiovascular failure with terlipressin after TCA intoxication refractory to catecholamines suggests a potential role for terlipressin as an adjunct vasopressor in severely hypotensive patients.

A randomised controlled trial of spinal manipulative therapy in acute low back pain

OBJECTIVE: To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption. METHODS: 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months. RESULTS: Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns. CONCLUSIONS: SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.

Characterization of inhibition of platelet function by paracetamol and its interaction with diclofenac and parecoxib

Aim: To characterize the inhibition of platelet function by paracetamol in vivo and in vitro, and to evaluate the possible interaction of paracetamol and diclofenac or valdecoxib in vivo. To assess the analgesic effect of the drugs in an experimental pain model. Methods: Healthy volunteers received increasing doses of intravenous paracetamol (15, 22.5 and 30 mg/kg), or the combination of paracetamol 1 g and diclofenac 1.1 mg/kg or valdecoxib 40 mg (as the pro-drug parecoxib). Inhibition of platelet function was assessed with photometric aggregometry, the platelet function analyzer (PFA-100), and release of thromboxane B2. Analgesia was assessed with the cold pressor test. The inhibition coefficient of platelet aggregation by paracetamol was determined as well as the nature of interaction between paracetamol and diclofenac by an isobolographic analysis in vitro. Results: Paracetamol inhibited platelet aggregation and TxB2-release dose-dependently in volunteers and concentration-dependently in vitro. The inhibition coefficient was 15.2 mg/L (95% CI 11.8 - 18.6). Paracetamol augmented the platelet inhibition by diclofenac in vivo, and the isobole showed that this interaction is synergistic. Paracetamol showed no interaction with valdecoxib. PFA-100 appeared insensitive in detecting platelet dysfunction by paracetamol, and the cold-pressor test showed no analgesia. Conclusions: Paracetamol inhibits platelet function in vivo and shows synergism when combined with diclofenac. This effect may increase the risk of bleeding in surgical patients with an impaired haemostatic system. The combination of paracetamol and valdecoxib may be useful in patients with low risk for thromboembolism. The PFA-100 seems unsuitable for detection of platelet dysfunction and the cold-pressor test seems unsuitable for detection of analgesia by paracetamol.

Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose -0.1-0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

Toxicity of diclofenac to Gyps vultures

Three endemic vulture species Gyps bengalensis, Gyps indicus and Gyps tenuirostris are critically endangered following dramatic declines in South Asia resulting from exposure to diclofenac, a veterinary drug present in the livestock carcasses that they scavenge. Diclofenac is widely used globally and could present a risk to Gyps species from other regions. In this study, we test the toxicity of diclofenac to a Eurasian (Gyps fulvus) and an African (Gyps africanus) species, neither of which is threatened. A dose of 0.8 mg kg(-1) of diclofenac was highly toxic to both species, indicating that they are at least as sensitive to diclofenac as G. bengalensis, for which we estimate an LD50 of 0.1-0.2 mg kg(-1). We suggest that diclofenac is likely to be toxic to all eight Gyps species, and that G. africanus, which is phylogenetically close to G. bengalensis, would be a suitable surrogate for the safety testing of alternative drugs to diclofenac.

Effect of meloxicam and diclofenac sodium on peri-implant bone healing in rats

Background: This study evaluated the effects of diclofenac sodium and meloxicam on peri-implant bone healing. Methods: Thirty male rats were divided into three groups: the control group (CG) received no drug; the diclofenac sodium group (DSG) received 1.07 mg/kg twice a day for 5 days; and the meloxicam group (MG) received 0.2 mg/kg daily for 5 days. A screw-shaped titanium implant was placed in the tibia. Fluorochromes, oxytetracycline (OxT), calcein (CA), and alizarin (AL), were injected at 7, 14, and 21 days, respectively, after implantation, and the animals were sacrificed 28 days after implant placement. The percentages of OxT-, CA-, and AL-labeled bone as well as the percentages of bone-to-implant contact (BIC), cortical bone area (CBA), and trabecular bone area (TBA) within the implant threads were evaluated. Results: Bone healing was delayed in the DSG during the first 14 days after implant placement (OxT-labeled bone: DSG: 5.3% +/- 7.3% versus CG: 13.2% +/- 9.8%, P= 0.002, and versus MG: 14.4% +/- 13.1%, P = 0.05). The percentages of BIC (DSG: 49.6% +/- 21.9%; MG: 67.1% +/- 22.8%; and CG: 68.1% +/- 22.8%) and CBA (DSG: 63.7% +/- 21.2%; MG: 82.7% +/- 12.4%; CG: 84.9% +/- 10.6%) were lower in the DSG compared to the MG and CG (P<0.001). The percentage of TBA was significantly greater in the DSG compared to the MG and CG (DSG: 36.3% +/- 21.2% versus MG: 17.3% +/- 12.7% and versus CG: 15.1% +/- 10.6%; P<0.001). Conclusion: Diclofenac sodium seemed to delay peri-implant bone healing and to decrease BIC, whereas meloxicam had no negative effect on peri-implant bone healing.

Amlodipine reduces the antimigratory effect of diclofenac in spontaneously hypertensive rats

Amlodipine, an antihypertensive drug, and diclofenac, an anti inflammatory drug, may generally be combined, particularly in elderly patients; therefore, the potential for their interaction is high. We aim to determine if amlodipine interferes with the antimigratory effect of diclofenac. For this, male spontaneously hypertensive rats (SHRs) were treated with either diclofenac (1 mg.kg(-1).d(-1), 15 d) alone or combined with amlodipine (10 mg.kg(-1).d(-1), 15 d). Leukocyte rolling, adherence, and migration were studied by intravital microscopy. Diclofenac did not change (180.0 +/- 2.3), whereas amlodipine combined (163.4 +/- 5.1) or not (156.3 +/- 4.3) with diclofienac reduced the blood pressure (BP) levels in SHR (183.1 +/- 4.4). Diclofenac and amlodipine reduced leukocyte adherence, migration, and ICAM-I expression, whereas only diclofenac reduced rolling leukocytes as well. Combined with amlodipine, the effect of the diclofenac was reduced. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, P-selectin, PECAM-1, L-selectin, or CD-18 expressions. No difference could be found in plasma concentrations of both drugs given alone or in association. In conclusion, amlodipine reduces leukocyte migration in SHR, reducing endothelial cell ICAM-1 expression. Amlodipine reduces the effect of the diclofenac, possibly by the same mechanism. A pharmacokinetic interaction as well as an effect on the other adhesion molecules tested could be discarded.

Effects of diclofenac and dexamethasone on horse experimental endotoxemia

Quinze eqüinos machos, da raça Mangalarga, com idades entre dois e três anos, foram utilizados para se avaliar os possíveis efeitos clínicos benéficos da administração de dexametasona ou diclofenaco sódico durante a endotoxemia experimental em eqüinos. Os animais foram divididos em três grupos de cinco animais cada: controle (C), diclofenaco sódico (SD) e dexametasona (DM). Todos os grupos receberam 0,1µg/kg de lipopolissarídeo de Escherichia coli 055:B5, durante 15 minutos, por via intravenosa mais: grupo SD - 2,2mg/kg de SD, por via oral, 60 minutos antes da infusão da endotoxina; grupo DM - 1,1mg/kg, por via intravenosa, 30 minutos antes da endotoxina; grupo C - 20ml de NaCl 0,9%, por via intravenosa, 30 minutos antes da endotoxina. O SD não preveniu a leucopenia, neutropenia e linfopenia ocorridas três horas após a indução da endotoxemia, porém a DM atenuou essas alterações. As taxas de proteínas plasmática e peritoneal, a concentração de glicose e de fósforo inorgânico e a contagem de células nucleadas totais peritoneais mantiveram-se inalteradas. O diclofenaco foi eficaz na prevenção da febre e alterações nos borborigmos intestinais enquanto que a dexametasona bloqueou as alterações no número de células inflamatórias em relação ao grupo controle.

Diclofenac sodium and Imipenem action on rat intestinal mucosa: a biomechanical and histological study

OBJETIVO: Avaliar as alterações histológicas e biomecânicas do diclofenaco de sódio na mucosa intestinal do rato e a associação com o uso de Imipenem. MÉTODOS: Foram estudados 240 ratos Wistar distribuídos aleatoriamente em quatro grupos experimentais: GI: 60 ratos tratados com injeção IM de soro fisiológico 0,9%; GII: 60 ratos tratados com injeção IM de diclofenaco de sódio na dose de 6mg/kg de peso por 4 dias; GIII: 60 ratos tratados com injeção IM de Imipenem na dose de 30 mg/kg de peso por 4 dias; GIV: 60 ratos tratados com injeção IM de soro fisiológico e diclofenaco de sódio nas doses acima. em cada grupo os animais foram posteriormente divididos em 4 momentos de 15 animais em cada um para sacrifício, respectivamente, no 4º, 7º, 14º e 21º dias após o início do tratamento. As alterações da cavidade abdominal, assim como as características histológicas e de força de ruptura do intestino delgado foram analisadas em cada momento, em cada grupo. RESULTADOS: Não foram encontradas alterações histológicas e biomecânicas nos animais do Grupo I nesse estudo. Lesões ulceradas na mucosa do intestino delgado foram observadas nos animais tratados com diclofenaco de sódio, assim como diminuição da força de ruptura. As lesões ulceradas encontradas foram prevenidas pelo uso de Imipenem. CONCLUSÃO: O diclofenaco de sódio induz lesões ulceradas na mucosa intestinal do rato que podem ser prevenidas pelo uso de Imipenem.

Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups (n = 10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C14H10C12NNaO2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis-Menten (K-M) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control. (C) 2008 Elsevier B.V. All rights reserved.

Photocatalytic decomposition of diclofenac potassium using silver-modified TiO(2) thin films

The effects of silver insertion on the TiO(2) photocatalytic activity for the degradation of diclofenac potassium were reported here. Techniques such as X-ray diffraction, scanning electron microscopy and UV-Vis spectroscopy were used to comprehend the relation between structure and properties of the silver-modified TiO(2), thin films obtained by the sol-gel method. The lattice parameters and the crystallinity of TiO(2) anatase phase were affected by inserted silver, and the film thickness increased about 4 nm for each 1 wt.% of silver inserted. The degradation of diclofenac potassium and by-products reached an efficiency of 4.6 mg(C) W(-1) when the material was modified with silver. Although the first step of degradation involves only the photochemical process related to the loss of the chlorine and hydrogen atoms. This cyclization reaction leads to the formation of intermediate, which degradation is facilitated by the modified material. (C) 2007 Elsevier B.V. All rights reserved.

Preparation of the Ca-diclofenac complex in solid state

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Thermal Behavior of Sr(II) and Ba(II)-Diclofenac Complexes in Solid State: Study of the Dehydration and Thermal Decomposition

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