Dipyrone Research Articles

Rapid, simple and accurate liquid chromatography–diode array detection validated method for the determination of dipyrone in solid and liquid dosage forms

The goal of this study was to develop and validate a liquid chromatography (LC) method for the rapid determination of dipyrone (metamizole sodium) in solid and liquid formulations. Samples were extracted with water and filtered prior to LC analysis. The analytical procedure involved reversed phase LC with a Zorbax SB C 18 column (5 μm particle size, 4.6 mm × 250 mm i.d.), isoctratic methanol/water (80/20, v/v) mobile phase with UV detection at 254 nm. The flow rate was 1 mL min −1 , injection volume was 100 μL and retention time of dipyrone was 3.3 min. The method was validated with respect to linearity, precision and accuracy. Calibration curves were linear in the range 0.5–100 μg mL −1 for analyte and the recoveries at three levels (10, 15 and 25 μg mL −1 ) ranged from 93 to 100%. All results for dipyrone were confirmed by liquid chromatography–mass spectrometry (LC–MS) and 1 H nuclear magnetic resonance (NMR) spectroscopy. Due to its simplicity and accuracy, the assay method is suitable for routine analysis of both solid and liquid formulations and seven retail samples were analyzed using the validated method.

A prospective randomized trial of Kotase® (Bromelain + Trypsin) in the management of post-operative abdominal wounds at the University of Nigeria Teaching Hospital Enugu, Nigeria

Background : Kotase ® is a combination systemic enzyme therapy that contains bromelain and trypsin. Bromelain is a crude extract of pineapple plant that contains mainly plant proteases. A multitude of actions have been ascribed to it including anti inflammatory properties. Aim : To evaluate the efficacy of bromelain/trypsin combination (Kotase ® ) in resolution of post laparotomy wound inflammation. Materials and Methods : The study is an open labeled study in which 111 patients were randomized in a 1:1 ratio to receive either Kotase ® or no kotase in their post op treatment. All the patients had major laparotomy wounds and were able to resume oral intake within 72 hours of surgery. The two groups of patients received all treatment necessary for their condition except with regards to analgesic and anti-inflammatory treatment. After commencement of oral intake, patients for Kotase treatment had two tablet of Kotase ® qid added to their post op drugs for a maximum of ten days or until the patient was discharged. Patients were assessed every day for operative wound pain, and inflammatory oedema. Also, the analgesic requirements and wound failure rates were assessed. Results : The two groups were matched with respect to demographic characteristics and case distribution. In the no treatment arm, the average post op inflammatory oedema decreased from 1.969mm on commencement of oral intake to 1.827mm on the 5 th day of measurement and 1.631mm by the time the patients were discharged. In the Kotase ® treatment group, the inflammatory oedema decreased from 1.959mm on the first day of drug treatment to 1.389mm by the 5 th day and 1.018mm by the time the patients were discharged. There was significant difference in the size of the oedema of the two groups on the 5 th day and by the time of discharge. The average visual analogue pain score of patients without Kotase ® decreased from 6.27 on the first day of oral intake to 3.65 by the 5 th day and 1.84 by the time the patients were discharged. The patients that had Kotase ® had an average pain score of 6.32 on the 1 st day and 2.45 on the 5 th day and 0.68 by the time of discharge. Again the drop in pain score was significantly more in the patients that had Kotase ® . Ten patients in the no Kotase ® arm needed extra doses of dipyrone in addition to the set down analgesics to control their pain while only one in the Kotase ® arm needed extra doses of analgesics to control his pain. There were 6 minor wound infections in each treatment arm and one wound breakdown in the no Kotase ® treatment group. There was no unexpected adverse reaction due to the use of Kotase ® . Conclusion : The results show the effectiveness of combination of bromelain and trypsin in reducing post operative inflammatory oedema and operation wound pain that accompany major laparotomy wounds. Keywords : bromelain, trypsin, post op inflammation, systemic enzyme therapy (SET) Journal of College of Medicine Vol. 10(2) 2005: 61-66

Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity.

A complex approach based on the use of test organisms belonging to different systematic groups (plants, invertebrates and vertebrates), as well as the nucleolar biomarker and the micronucleus test on their cells, was applied to assess the toxicity, cytotoxicity and genotoxicity of two pharmaceutical substances (metamizole sodium and acetylsalicylic acid) applied at ic(50) concentrations for mammalian cells. The compound acetylsalicylic acid was evaluated at a concentration (1.6 x 10(3) mg l(-1)) that was non-toxic for bioassays based on fish (Carassius auratus gibelio) and hydra (Hydra attenuata) and acutely toxic for bioassays with ceriodaphnia (Ceriodaphnia affinis) and onion (Allium cepa). The metamizole sodium solution (6.25%) demonstrated acute toxicity for the whole set of test organisms. Both drugs, after their 30-360 min influence on the test organisms, first changed the nucleolar size in plant and animal cells (i.e. the transcriptional activity of ribosomal genes was affected most significantly). Moreover, the metamizole sodium solution caused nucleolar structural damage in 90% of hydra cells as early as after 30 min of exposure. The acetylsalicylic acid solution inhibited essentially the rate of cell division in the meristem of onion roots (the mitotic index decreased to 9.6 per thousand, as compared 51.7 per thousand for the control). The carp incubation and the onion germination in the acetylsalicylic acid solution showed a reproducible increase in the frequency of cells with micronuclei (2 and 5.5 times, respectively) and double nuclei (3 and 1.5 times, respectively). The approach described herein may be applied for obtaining rapid, cost-efficient and useful supplementary data on different types of toxicity for marketed drugs as well as for drugs under development.

Analgesic effects of interpleural bupivacaine with fentanyl for post-thoracotomy pain

Objective: The analgesic effect of bupivacaine/fentanyl with epinephrine given interpleurally after thoracotomy was investigated in a randomized placebo and intravenous controlled study. Design: Prospective clinical study. Setting: University teaching hospital. Participants: Sixty American Society of Anesthesiologists physical status II and III patients scheduled for posterolateral thoracotomy with general anesthesia. Interventions: Patients were randomly divided into 4 groups to receive either 0.5% bupivacaine/1.5 μg/kg of fentanyl with 5 μg/mL of epinephrine (n = 15, group IPBF), 0.5 % bupivacaine with 5 μg/mL of epinephrine (n = 15, group IPB), or saline (n = 15, group IPS) in a total volume of 15 to 20 mL in 60 seconds by an interpleural catheter placed at the end of surgery by direct vision. The same volume of bupivacaine 0.25% and 1.5 μg/kg of fentanyl with 5 μg/mL of epinephrine to group IPBF, bupivacaine 0.25% with 5 μg/mL of epinephrine to group IPB or saline to group IPS was injected through the interpleural catheter every 6 hours for 48 hours postoperatively. Intravenous fentanyl (n = 15, group IVF) and interpleural saline groups received 1.5 μg/kg of fentanyl intravenously at the first complaint of pain. All patients also received patient-controlled analgesia (PCA) with fentanyl for 48 hours postoperatively. Metamizol sodium was used as a rescue analgesic. Measurements and Main Results: Adequacy of pain relief was evaluated with the “Prince Henry Pain Scale” and visual analog pain scale. Fentanyl consumption via PCA and complications were evaluated for 48 hours. Visual analog scale scores were significantly higher in the interpleural saline group at 4 and 12 hours (6.6 ± 1.2 and 5.0 ± 2.1, respectively) postoperatively. Significantly more patients in the IPBF group had lower pain scores during coughing and deep breathing. Fentanyl consumption via PCA device was significantly higher in the intravenous fentanyl group (1,069 ± 96.9 μg) than the interpleural groups (577.3 ± 72.2 μg, 651.1 ± 61.9 μg, and 601.0 ± 22.6 μg in IPBF, IPB, and IPS groups, respectively). Conclusion: It is concluded that total fentanyl consumption via PCA decreased in all interpleural groups, but pain during coughing and deep breathing was significantly reduced in only the interpleural bupivacaine/fentanyl with epinephrine group.

Comparison of cizolirtine citrate and metamizol sodium in the treatment of adult acute renal colic: A randomized, double-blind, clinical pilot study

Background: Renal colic causes excruciating pain that provides a good clinical model of acute pain for the development of new analgesics.Objective: The purpose of the study was to compare the analgesic efficacy and tolerability of cizolirtine citrate and metamizol sodium in adult acute renal colic.Methods: This Phase II, randomized, double-blind, clinical pilot study was conducted in the emergency departments of 6 general hospitals in the Czech Republic between October 2000 and February 2001. Male and female patients aged 18 to 65 years and presenting with hematuria and moderate to severe pain due to suspected renal colic starting within the 24 hours before presentation were eligible. Patients were randomized to receive a single IV dose of cizolirtine 350 mg or metamizol 2500 mg, administered by slow infusion over 15 minutes. Both doses were maximal for the respective drugs to attain adequate analgesia. Use of rescue medication with butorphanol was allowed 30 minutes after study drug administration. Pain intensity was assessed at various time points during the following 360 minutes using a 100-mm visual analog scale (VAS) and a verbal categoric scale. In addition, a specific verbal categoric scale was used to rank pain relief. Physical examinations, laboratory tests, and questioning for adverse events addressed drug tolerability.Results: Sixty-four patients (50 men, 14 women; mean [SD] age, 44.21 [12.29] years; mean [SD] body mass index, 25.97 [3.38] kg/m2) were enrolled. Physical examination findings and mean VAS pain intensity scores at baseline (mean [SD], 79.42 [7.89] mm and 82.59 [10.50] mm in the cizolirtine and metamizol groups, respectively) were similar in both groups. After 30 minutes, the mean (SD) scores were 33.84 (25.15) mm and 25.41 (24.51) mm, respectively. This difference was not statistically significant, and the noninferiority of cizolirtine with respect to the comparator could not be established. However, the proportion of patients that showed satisfactory pain relief (ie, decrease of ≥50% in VAS pain intensity score compared with baseline) at 30 minutes in the cizolirtine group was fairly high (64.5%), which means relevant analgesic activity. Both treatments were well tolerated; 6 adverse events were reported in 5 patients (7.8%), and all were considered as not treatment related.

Metamizole Sodium-Induced Severe Aplastic Anemia and its Recovery with a Short-Course Steroid Therapy

The authors treated a girl with severe aplastic anemia that developed following urinary tract infection. She was referred to our hospital for bone marrow transplantation. The detailed medical history of the patient revealed iatrogenic metamizole sodium overdose that was given during her infection. She responded to a 3-day, high-dose methylprednisolone therapy and consequent conventional dose steroid. The authors observed at first partial and subsequently complete remission of all the hematologic parameters of the patient within 30 days and 4 months, respectively. This case suggests that the history of drug use should be questioned carefully in the patients with aplastic features. Steroid treatment may be an appropiate alternative therapy for aplastic anemia if associated drug use is detected in the medical history.

Interaction between metamizol and tramadol in a model of acute visceral pain in rats

Tramadol (TRM) and metamizol (MTZ) are drugs with complex mechanisms of action, extensively used in combination in pain management. In the present investigation we have evaluated the interaction between MTZ:TRM in the ethacrinic acid writhing test in rats. Dose–response curves (s.c.) were obtained for each drug individually, combined in fixed potency ratios (1:0.3, 1:1, 1:3), and for MTZ in presence of a fixed-dose of TRM (3.5 mg/kg). Interactions were analysed using isobolograms, interaction indexes (INT-I) and ANOVA. We used naloxone (1 mg/kg s.c.) to determine the opioid-component of the effects (ED 80). Isobolograms demonstrated antagonism at the ED 20, for 1:0.3 and 1:3 mixtures ( p<0.01), whereas 1:1 was additive. At the ED 50 and ED 80 all combinations showed synergy. Fixed-dose experiments demonstrated that treatment ( p<0.0001), dose ( p<0.0001), and their interaction ( p<0.0001) were statistically significant. Naloxone partially antagonized TRM (67%), but not MTZ; the percentage reversal of the combinations was directly related to the dose of TRM in the combination. The results show that the MTZ:TRM interaction on antinociception is synergistic or antagonistic depending on the level of effect. Synergy is demonstrated at 50% or higher levels, thus supporting the results obtained in humans by our group. Below the ED 50 antagonism or additivity is present depending on the ratio of the combination. The mechanisms of the interaction remain unknown.

Linear regression analysis and its application to the multivariate spectral calibrations for the multiresolution of a ternary mixture of caffeine, paracetamol and metamizol in tablets

The multivariate spectral calibration methods, tri-linear regression-calibration (TLRC) and multi-linear regression-calibration (MLRC) were developed for the multiresolution of a ternary mixture of caffeine (CAF), paracetamol (APAP), metamizol (MET), which have closely overlapped in the spectra. The calibration algorithms were briefly described for the three-component system, CAF–APAP–MET. By using the various synthetic mixtures of three compounds, the validity of the TLRC and MLRC methods was confirmed and applied to the real samples containing the above-mentioned compounds in two different commercial tablet formulations. The TLCR and MLRC methods which are very rapid, easy to apply, yet not expensive, are powerful tools with very simple mathematical contents for multiresolution of the three- or multi-component mixture systems. The data treatments were carried out by the maple v, excel and spss 10.0 Softwares. The obtained results were successfully compared with each other as well as with those obtained by other literature methods.

Dipyrone and agranulocytosis: what is the risk?

Dipyrone and agranulocytosis: what is the risk?

Effect of antipyretics on polymorphonuclear leukocyte functions in children

The aim of this study was to investigate whether fever and antipyretic drugs had an adverse effect on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity). Twenty febrile children with an axillary temperature of 39–40 °C and 20 healthy children without fever were included. Polymorphonuclear leukocytes were isolated. The effects of in vitro addition of antipyretic drugs (acetaminophen, metamizole sodium, nimesulid and ibuprofen) on PMN functions were tested. Phagocytic activity was assayed by the ingestion of yeast cells by PMNs and intracellular killing activity by the ingestion of yeast cells (stained blue) killed by PMNs. PMNs derived from febrile children exhibited better phagocytic activity when ibuprofen was added. In contrast, phagocytic activity was enhanced when acetaminophen, metamizole sodium or nimesulid was added in children without fever. Intracellular killing activity was enhanced when ibuprofen or metamizole sodium was added in children without fever. We conclude the antipyretic drugs at safely achievable concentrations do not suppress PMN function in vitro.

Exanthema to metamizole

Exanthema to metamizole

Exanthema to metamizole

AllergyVolume 56, Issue 3 p. 262-263 Exanthema to metamizole† D. Quiñones Estévez, D. Quiñones Estévez Centro Médico GijónPlaza Seis de Agosto n° 3, bajo33206 – Gijón (Asturias)SpainSearch for more papers by this authorC. Fernández Schmitz, C. Fernández Schmitz Centro Médico GijónPlaza Seis de Agosto n° 3, bajo33206 – Gijón (Asturias)SpainSearch for more papers by this author D. Quiñones Estévez, D. Quiñones Estévez Centro Médico GijónPlaza Seis de Agosto n° 3, bajo33206 – Gijón (Asturias)SpainSearch for more papers by this authorC. Fernández Schmitz, C. Fernández Schmitz Centro Médico GijónPlaza Seis de Agosto n° 3, bajo33206 – Gijón (Asturias)SpainSearch for more papers by this author First published: 20 December 2001 https://doi.org/10.1034/j.1398-9995.2001.00956.xCitations: 3 † First case of nonpigmented fixed exanthema. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume56, Issue3March 2001Pages 262-263 RelatedInformation

Modified microelectrodes and multivariate calibration for flow injection amperometric simultaneous determination of ascorbic acid, dopamine, epinephrine and dipyrone.

Flow injection amperometric quantification of ascorbic acid (AA), dopamine (DA), epinephrine (EP) and dipyrone (DI) in mixtures (in the microgram g-1 range) was successfully performed by using an array of microelectrodes with units modified by the electrodeposition of different noble metals, together with multivariate calibration analysis. The four groups of microelectrodes utilized included a pure gold electrode and electrodes modified by electrodeposition of platinum, palladium or a mixture of platinum + palladium. The array of microelectrodes was inserted in a flow cell and the amperometric data acquisition was performed with a four-channel potentiostat. The analysis of the resulting signals was carried out by a multivariate calibration method, using a group of 16 standard mixtures selected by a two-level factorial design. The analysis of synthetic samples and pharmaceutical compounds containing AA and DI led to very similar values to those obtained by the classical iodimetric analysis. The average absolute errors (in microgram g-1) calculated for each analyte were 0.3, 0.2, 0.4 and 0.4 for AA, DA, EP and DI, respectively.

Study of Load Capacity of Avicel PH-200 and Cellactose, Two Direct Compression Excipients, Using Experimental Design

The load capacity of two excipients, a large particle size grade of microcrystalline cellulose (Avicel™ PH-200) and a coprocessed material composed of lactose and pulverized cellulose (Cellactose™) was determined using a model mix with Dipyrone (metamizol sodium) and experiments planned by design of experiments. A multiple-regression model was proposed, and as a result, a new parameter, called specific load capacity SLC was obtained. This constant can be determined for other excipients and drugs; it depends only on the excipient and the drug used.

Lubricant Susceptibility of Cellactose and Avicel PH-200: A Quantitative Relationship

The lubricant susceptibility of two direct compression excipients, Avicel PH-200 and Cellactose, was determined using a model mix with metamizol sodium (dipyrone) and designed experiments to obtain a quantitative relationship by multiple regression. As a result, a new constant called specific lubricant sensibility Ls, is proposed for the comparison of lubricant susceptibility in other drug-excipient systems.

The antinociceptive effect of PAG-microinjected dipyrone in rats is mediated by endogenous opioids of the rostral ventromedial medulla

Microinjection of non-opioid analgesics, such as dipyrone (DIP), into the periaqueductal gray matter (PAG) in rats causes an inhibition of nociceptive circuits in the spinal cord. We have herein investigated whether this effect is mediated by opioidergic mechanisms in the rostral ventromedial medulla (RVM), which is an important relay between the PAG and the spinal cord. The responses of spinal wide-dynamic-range neurons to noxious stimulation of their receptive field (RF) were inhibited by microinjection of DIP (100 μg/0.5 μl) into PAG. Subsequent microinjection of naloxone (NAL; 0.5 μg/0.5 μl) into RVM reversed this inhibition. The present and previous results suggest that non-opioid analgesics, as well as opiates, inhibit nociception by activating descending opioidergic mechanisms in PAG and RVM.

Mutagenicity assay in Salmonella and in vivo sister chromatid exchange in bone marrow cells of mice for four pyrazolone derivatives

Phenylbutazone (PB), oxyphenbutazone (OPB), antipyrine (AP) and dipyrone (DP) are four important pyrazolone derivatives mainly used as anti-inflammatory, antipyretic and analgesic drugs. At present these are the most widely used pyrazolone derivatives throughout the world. The widespread use of these drugs are of great concern for human health problems. In the present study these four drugs were tested in mutagenicity assays in Salmonella strains TA97a, TA98, TA100 and TA102 using a plate incorporation assay both with and without S-9 mix and for in vivo sister chromatid exchanges (SCE) in bone marrow cells of mice. The first three drugs were negative in all the tester strains but dipyrone showed a weak mutagenic activity at higher concentrations in all four strains both with and without metabolic activation. In the in vivo SCE assay in male mice, all four drugs showed a statistically significant increase in SCE in bone marrow cells when compared with control.

Naloxone partial reversal of the antinociception produced by dipyrone microinjected into the periaqueductal gray of rats. Possible involvement of medullary off- and on-cells

Medullary off- and on-cells have been proposed to inhibit and facilitate, respectively, nociceptive transmission. Upon hearing the tail in lightly anesthetized rats, the tail flick (TF) reflex occurs only after off-cells decrease and on-cells increase their activity. Dipyrone (DIP) microinjection (100 μg/0.5 μl) into the periaqueductal gray (PAG) caused retardation in the off-cell pause, on-cell burst and corresponding TF. This effect was partly reverted by naloxone given i.v. (1 mg/kg) or microinjected into PAG (5 μg/0.5 μl). These results suggest that endogenous opioids are partly responsible for the central antinociceptive action of DIP, and that such action involves medullary off- and on-cells.

Naloxone partial reversal of the antinociception produced by dipyrone microinjected into the periaqueductal gray of rats. Possible involvement of medullary off- and on-cells

Medullary off- and on-cells have been proposed to inhibit and facilitate, respectively, nociceptive transmission. Upon hearing the tail in lightly anesthetized rats, the tail flick (TF) reflex occurs only after off-cells decrease and on-cells increase their activity. Dipyrone (DIP) microinjection (100 μg/0.5 μl) into the periaqueductal gray (PAG) caused retardation in the off-cell pause, on-cell burst and corresponding TF. This effect was partly reverted by naloxone given i.v. (1 mg/kg) or microinjected into PAG (5 μg/0.5 μl). These results suggest that endogenous opioids are partly responsible for the central antinociceptive action of DIP, and that such action involves medullary off- and on-cells.

Dipyrone and diclofenac IM and IV compared

Dipyrone and diclofenac IM and IV compared