• Title, Summary, Keyword: diclofenac

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A Behavioral Study of Promethazine Interaction with Analgesic Effect of Diclofenac: Pain Combination Therapy

  • Amidi, Niloofar;Izadidastenaei, Zohreh;Araghchian, Malihe;Ahmadimoghaddam, Davoud
    • Journal of Pharmacopuncture
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    • v.23 no.1
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    • pp.18-24
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    • 2020
  • Objectives: Pain is considered as a cause of sickness and the most prevalent symptom which makes people visit a physician. Nowadays, combination therapy is becoming useful to relieve chronic and postsurgical pain. The aim of this study was to study the promethazine (as an antihistamine) interactions with antinociceptive effect of diclofenac (as a non-steroidal anti-inflammatory drugs). Methods: In initial part of the study, we investigate the analgesic effect of diclofenac. Using writhing test, we demonstrate that diclofenac significantly reduces writhe response induced by acetic acid in a dose-dependent manner. In this study, we evaluate the combination effect of promethazine on diclofenac analgesic effect. Results: We observed that diclofenac inhibited pain in the dose dependent manner which means that by increasing dose of diclofenac a significant decrease in pain was observed. This experimental setup allowed calculation of the dose that caused 50% antinociception (ED50) for diclofenac. The ED50 for diclofenac in this study was determined to be 9.1 mg/kg according our previous study. Additionally, promethazine was showed a dose-dependent inhibition of writhes. The combination of different doses of promethazine (2, 4, 6 mg / kg) with diclofenac ED50 (9.1 mg / kg) was injected to mice. Promethazine 4 and 6 mg / kg in combination with diclofenac had significantly led to increase analgesic effect of diclofenac. Conclusion: In conclusion, these results add important information to the existing knowledge on combination of diclofenac and antihistamine in pain therapies to be used in clinical practice and maybe helpful in designing the future guidelines.

Determination of diclofenac and its metabolites in human urine by GC-MS (GC-MS를 이용한 소변 중 Diclofenac 및 대사체 분석)

  • Jeong, Jee-Hye;Huh, Hun;Lee, Won Woong;Hong, Jongki
    • Analytical Science and Technology
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    • v.21 no.6
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    • pp.510-517
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    • 2008
  • This study has been described the metabolism and excretion in a healthy male urine collected for 26hrs after oral administration of diclofenac. To detect conjugated metabolites of diclofenac, urine sample was acid-hydrolyzed under the conditions of 6M-HCl at over $110^{\circ}C$ for 1hr. During the acidic hydrolysis process, diclofenac and its metabolites were converted into their corresponding lactam-ring through dehydration reaction. As results of chemical conversion by means of hydrolysis, the structures of diclofenac and its metabolites were also changed acidic to basic forms. However, lactam-ring was degraded by hydroxyl ion at basic condition. Thus, the extraction rate of dehydrated diclofenac and its metabolites was not favored at basic condition. For the determination of trace amounts of diclofenac and its metabolites in urine, trimethylsilylation (TMS) with MSTFA was applied and followed by analysis with gas chromatograph-mass spectrometer. In this study, four metabolites that are formed by the hydroxylation of parent drug were mainly detected. Each metabolite was tentatively identified by both interpretation of mass spectra and comparison with previously reported results. In addition, time profile of urinary excretion rate for parent drugs and metabolites was studied. Finally, the metabolic pathway of diclofenac was suggested on the basis of the elucidation of its metabolites and excretion profiles.

Physicochemical Characterization and In Vivo Evaluation of Thermosensitive Diclofenac Liquid Suppository

  • Yong, Chul-Soon;Choi, Young-Kwon;Kim, Yong-Il;Park, Byung-Joo;Quan, Qi-Zhe;Rhee, Jong-Dal;Kim, Chong-Kook;Choi, Han-Gon
    • Archives of Pharmacal Research
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    • v.26 no.2
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    • pp.162-167
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    • 2003
  • Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers. since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

Solubility and In vivo Absorption Enhancement of Diclofenac Sodium by ${\beta}-Cyclodextrin$ Complexation (${\beta}$-시클로덱스트린과의 포접에의한 디플로페낙나트륨의 용해도 및 생체흡수율 증가)

  • Lee, Kyung-Tae;Kim, Jong-Hwan;Kim, Joo-Il;Kim, Seung-Jo;Seo, Hee-Kyoung;Seo, Seong-Hoon
    • Journal of Pharmaceutical Investigation
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    • v.26 no.3
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    • pp.169-174
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    • 1996
  • Inclusion complexes of diclofenac sodium with ${\beta}-cyclodextrin$ were prepared in aqueous solution, alkaline solution and solid phase. The interaction of diclofenac sodium with ${\beta}-cyclodextrin$ in pH 9.0 alkaline solution was evaluated by the solubility method and the instrumental analysis such as thermal analysis, infrared spectroscopy, X-ray diffractometry. The solubility of diclofenac sodium was increased linearly with the increase in the concentration of ${\beta}-cyclodextrin$up to 0.15 mol and showed that the aqueous solubility rate of diclofenac sodium was significantly increased by complex with ${\beta}-cyclodextrin$. The optimum composition of this complex was one molecule of ${\beta}-cyclodextrin$ included 1.59 molecular weight of diclofenac sodium as a guest molecule. The pharmacokinetic parameters of the diclofenac sodium and the complex with ${\beta}-cyclodextrin$ were studied in rats by oral route. $T_{max}$ between drug alone and inclusion complex showed significant difference to be 120 minute and 20 minute respectively. Both of $C_{max}$ and AUC of inclusion complex was about 40% higher than drug alone. It is estimated from the data in this study that complexation of diclofenac sodium with ${\beta}-cyclodextrin$ increased the absorption rate and improved the bioavalability of the diclofenac sodium by the formation of a water-soluble complexes.

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Effect of Glutamine on the Diclofenac Induced Bacterial Translocation and Lipid Peroxidation (Diclofenac에 의해 유발된 장내세균전위와 지질과산화에 대한 글루타민의 효과)

  • Kim, Eun-Jeong;Kim, Jeong-Wook
    • YAKHAK HOEJI
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    • v.49 no.2
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    • pp.128-133
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    • 2005
  • The aim of this study was to examine whether administration of glutamine are able to prevent the NSAID induced bacterial translocation and lipid peroxidation in the rats. The an imals with glutamine were fed with L-glutamine for 5 days before diclofenac administration (100 mg/kg orally). 48 hour after diclofenac administration, intestinal permeability, serum biochemical profiles, and malondialdehyde levels of ileum were measured for evaluation of gut damage. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric Iymph nodes, liver, spleen and kidney and malondialdehyde levels in liver, spleen, kidney and plasma were measured. Diclofenac caused the gut damage, enteric bacterial overgrowth, increased bacterial translocation and increased lipid peroxidation. Co-administration of glutamine reduced the gut damage, enteric bacterial overgrowth, bacterial translocation and lipid peroxidation induced by diclofenac. This study suggested that glutamine might effectively prevent non-steroidal anti-inflammatory drug induced bacterial translocation and lipid peroxidation in the rat.

The Changes in Intestinal Damage and Bacterial Translocation with Time after Administration of Diclofenac (Diclofenac 투여 후 시간경과에 따른 장손상과 장내세균전위의 변화)

  • Kim, Eun-Jeong;Kim, Jeong-Wook
    • YAKHAK HOEJI
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    • v.52 no.4
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    • pp.293-298
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    • 2008
  • Non-steroidal anti-inflammatory drug (NSAID)-induced gut damage and bacterial translocation (BT) have not been studies well, especially from the perspective of time after administration of NSAIDs. We therefore examined these changes in animals. The study was performed on 5 groups of rat; a control group (group A) and diclofenac groups (groups B, C, E, and F). Rats in the diclofenac groups were orally administered diclofenac sodium before intestinal permeability (IP) measurement (group B, 1 h before measurement; group C, 10 h before; group D, 22 h before; and group E, 52 h before). The IP, stool pellet number, serum biochemical profile, enteric bacterial number, and BT in the mesenteric lymph nodes (MLNs), liver, spleen, kidney and heart were measured. The administration of diclofenac resulted in significantly increased IP, caused intestinal protein loss, decreased stool pellet number, caused enteric bacterial overgrowth and increased BT in multiple organs in groups A, B, C, and D. IF, intestinal protein loss, and the BT in the liver and the spleen in group E were decreased than those in group D. There were no differences in the other parameters between group D and E. In the recovery phase of the diclofenac-induced gut damage, enteric bacterial overgrowth and BT in the kidneys and the heart did not change while the BT in the reticuloendothelial systems such as in the MLNs and liver was decreased.

Comparison of safety and analgesic efficacy of diclofenac sodium with etodolac after surgical extraction of third molars: a randomized, double-blind, double-dummy, parallel-group study

  • Vaghela, Jitendra H.;Shah, Jigna H.;Patel, Jaladhi H.;Purohit, Bhargav M.
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.20 no.1
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    • pp.19-27
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    • 2020
  • Background: Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3-5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies. Methods: We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome. Results: Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants. Conclusion: Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

Removal of Diclofenac, Ibuprofen and Naproxen using Oxidation Processes (산화공정에서의 Diclofenac, Ibuprofen 및 Naproxen의 제거특성 평가)

  • Son, Hee-Jong;Yoo, Soo-Jeon;Hwang, Young-Do;Roh, Jae-Soon;Yoo, Pyung-Jong
    • Journal of Korean Society of Environmental Engineers
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    • v.31 no.10
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    • pp.831-838
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    • 2009
  • In order to evaluate a removal characteristic of diclofenac, ibuprofen and naproxen by oxidizing agents, $Cl_2,\;O_3$ and $O_3/H_2O_2$ are used as oxidants in this study. In case of that $Cl_2$ is used for oxidizing pharmaceuticals, ibuprofen is not removed entirely at $Cl_2$ dose range of 0.5~5.0 mg/L for 60 minutes, however, removal tendency of diclofenac and naproxen are so obviously at $Cl_2$ dose higher than 0.5 mg/L. In addition, as $Cl_2$ dose and contact time are increased, the removal rate of diclofenac and naproxen is enhanced. When $O_3$ is used as oxidizing agent, ibuprofen is not eliminated at $O_3$ dose range of 0.2~5.0 mg/L. On the contrary, 72~100% of diclofenac and 49~100% of naproxen are removed at $O_3$ dose of 0.2~5.0 mg/L. From experiments using $O_3/H_2O_2$ as an oxidant, we can find that $O_3/H_2O_2$ is much more effective than $O_3$ only for removal of diclofenac and naproxen. Moreover, the efficiency is raised according to increase of $H_2O_2$ dose, however, experiments using $O_3/H_2O_2$ show that oxidation of pharmaceuticals is less effective as $H_2O_2$ to $O_3$ ratio increased to above approximately 1.0. On reaction rate constant and half-life of diclofenac, ibuprofen and naproxen depending on $Cl_2$, $O_3$ and $O_3/H_2O_2$ dose, an oxidation of pharmaceuticals by $Cl_2$ and $O_3$ particularly has a comparatively high reaction rate constant and short half-life comparing $O_3/H_2O_2$. From above results, we can fine that diclofenac and naproxen can be easily eliminated in oxidation processes.

Diclofenac Inhibits $IFN-{\gamma}$ Plus Lipopolysaccharide-Induced iNOS Gene Expression via Suppression of $NF-{\kappa}B$ Activation in RAW 264.7 Macrophages

  • Bae, So-Hyun;Ryu, Young-Sue;Hong, Jang-Hee;Park, Jin-Chan;Kim, Yong-Man;Seok, Jeong-Ho;Lee, Jae-Heun;Hur, Gang-Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.6
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    • pp.521-527
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    • 2001
  • Diclofenac, a phenylacetic acid derivative, is a widely used non-steroidal anti-inflammatory drug (NSAID) to provide effective relief of inflammation and pain. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. We examined the inhibitory effects of diclofenac on the induction of iNOS in RAW 264.7 macrophages which were activated with lipopolysaccharide (LPS) plus interferon-gamma $(IFN-{\gamma}).$ Treatment of RAW 264.7 cells with diclofenac and other NSAIDs (aspirin and indomethacin) significantly inhibited NO production and iNOS protein expression induced by LPS plus $IFN-{\gamma}.$ Also, diclofenac but not aspirin and indomethacin, inhibited iNOS mRNA expression and nuclear factor-kappa B $(NF-{\kappa}B)$ binding activity concentration-dependently. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked to a CAT reporter gene revealed that only diclofenac inhibited the iNOS promoter activity induced by LPS plus $IFN-{\gamma}$ through the $NF-{\kappa}B$ sites of iNOS promoter. Taken together, these suggest that diclofenac may exert its anti-inflammatory effect by inhibiting iNOS gene expression at the transcriptional level through suppression of $NF-{\kappa}B$ activation.

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Development of Poloxamer-Based Solid Suppository Containing Diclofenac Sodium (폴록사머를 이용한 디클로페낙 고형 좌제의 개발)

  • Yong, Chul-Soon;Oh, Yu-Kyoung;Kim, Jung-Ae;Kim, Yong-Il;Park, Sang-Man;Yang, Joon-Ho;Rhee, Jong-Dal;Choi, Han-Gon
    • Journal of Pharmaceutical Investigation
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    • v.34 no.2
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    • pp.91-94
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    • 2004
  • To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution ad dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based sold suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Ver small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about $32^{\circ}C$ was a sold for at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue colo of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/ P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in thε rectum for at least 4 h. Our results indicated that the poloxamer-based sold suppository with P 124 and P 188 would be a candidate of rectal dosage form for diclofenac sodium.