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David Mauleon - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of Dexketoprofen trometamol in healthy volunteers after single and repeated oral doses
The Journal of Clinical Pharmacology, 1998Co-Authors: Manel J Barbanoj, Ignasi Gich, Remei Artigas, Digna Tost, Cristina Moros, Rosa M Antonijoan, Luisa M Garcia, David MauleonAbstract:The pharmacokinetics of Dexketoprofen trometamol were evaluated in two studies using healthy volunteers. In the first study, the relative bioavailability of a single oral capsule of Dexketoprofen free acid 25 mg or Dexketoprofen trometamol 25 mg (given as 37 mg of the trometamol salt) was compared to ketoprofen 50 mg in 18 healthy volunteers. In the second study, the pharmacokinetics and tolerability of oral Dexketoprofen trometamol in tablet form were evaluated after either a single 25 mg dose (24 volunteers) or a repeated dose of 25 mg twice daily for 7 days (12 volunteers). The absorption of Dexketoprofen from Dexketoprofen trometamol capsules was bioequivalent to that of ketoprofen. On the other hand, the extent of absorption of Dexketoprofen free acid was significantly lower than that for ketoprofen. Dexketoprofen trometamol showed the most rapid absorption rate, with highest Cmax and shortest tmax values, whereas Dexketoprofen free acid had the slowest absorption rate, and ketoprofen had an intermediate absorption rate. After repeated-dose administration of Dexketoprofen trometamol, the pharmacokinetic parameters were similar to those obtained after single doses, indicating that no drug accumulation occurred. Dexketoprofen trometamol was well tolerated, with no clinically relevant adverse events reported.
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comparison of Dexketoprofen trometamol and ketoprofen in the treatment of osteoarthritis of the knee
The Journal of Clinical Pharmacology, 1998Co-Authors: Juan Beltran, Remei Artigas, E Martinmola, Manuel Figueroa, Josep Granados, Raimon Sanmarti, Ferran Torres, Monica Forns, David MauleonAbstract:: Dexketoprofen, the active enantiomer of the racemic compound ketoprofen, is a new nonsteroidal antiinflammatory drug (NSAID) of the arylpropionate family. The efficacy and safety of Dexketoprofen trometamol were compared with the equivalent enantiomeric dose of ketoprofen in a multicenter, randomized, double-blind 3-week trial of adult outpatients with pain due to osteoarthritis of the knee. After a washout period of 7-15 days, patients were randomly assigned to receive either Dexketoprofen trometamol 25 mg tid (N = 89) or ketoprofen 50 mg tid (N = 94). Of the 183 patients enrolled, two were lost to follow-up. At the end of treatment (3 weeks), the main efficacy outcome measures were significantly better in the Dexketoprofen trometamol group than in the ketoprofen group. In addition, overall physician assessment indicated that 75% of the Dexketoprofen group had improved compared with 50% of the ketoprofen patients. There were fewer adverse events in the Dexketoprofen treatment group, but the difference did not reach statistical significance. These results demonstrate that Dexketoprofen trometamol 25 mg tid is more effective than ketoprofen 50 mg tid in short-term symptomatic treatment of knee osteoarthritis and suggest that the tolerability of Dexketoprofen trometamol is more favorable than ketoprofen. Therefore, the substitution of Dexketoprofen for racemic ketoprofen may be advantageous in clinical practice.
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comparison of the efficacy and tolerability of Dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea
The Journal of Clinical Pharmacology, 1998Co-Authors: Miguel Ezcurdia, Remei Artigas, Ferran Torres, Francisco Javier Cortejoso, Ramon Lanzon, Francisco Javier Ugalde, Alfonso Herruzo, Francisca M Fernandez, David MauleonAbstract:: Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with Dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that Dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, Dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of Dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of Dexketoprofen or between Dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo.
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clinical comparison of Dexketoprofen trometamol and dipyrone in postoperative dental pain
The Journal of Clinical Pharmacology, 1998Co-Authors: Jose Vicente Bagan, Remei Artigas, Monica Forns, Sebastian Lopez J Arranz, Eduardo Valencia, Joseba Santamaria, Isabel Eguidazu, Manuel Horas, Antonio Zapata, David MauleonAbstract:: A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive Dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post dose to the end of the 6-h observation period, both doses of Dexketoprofen trometamol had higher pain relief scores than dipyrone: Between 3 and 6 h the differences were statistically significant. In addition, peak measures (PIDmax and PARmax ) were statistically superior after both doses of Dexketoprofen trometamol compared to dipyrone. The overall efficacy assessed at the end of the first-dose phase was rated as good or excellent by 90%, 83.3%, and 70% of patients receiving Dexketoprofen trometamol 25 mg, Dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The number of patients who required remedication during the 6-h period was significantly lower in both Dexketoprofen groups. Repeated-dose data were also obtained. No significant differences were found in the efficacy after repeated doses, the number of doses taken, or the mean time elapsed between doses. The overall efficacy at the end of the repeated-dose phase was rated as good or excellent by 84.2%, 66.7%, and 70% of patients receiving Dexketoprofen trometamol 25 mg, Dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The frequency of adverse events was similar for all treatments and no serious adverse events were reported during the study.
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clinical comparison of Dexketoprofen trometamol ketoprofen and placebo in postoperative dental pain
The Journal of Clinical Pharmacology, 1998Co-Authors: Mark Mcgurk, Remei Artigas, P Robinson, V Rajayogeswaran, M De Luca, A Casini, G Munoz, David MauleonAbstract:: The efficacy and tolerability of single doses of Dexketoprofen trometamol 12.5 mg, 25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind, randomized, placebo-controlled study of 210 patients with moderate to severe pain after removal of one mandibular impacted third molar tooth. Pain intensity and pain relief were monitored for 6 h after administration of medication using visual analogue and verbal rating scales. All four active treatments were significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50 mg produced an analgesic effect within 30 min of administration and their effect persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to those of the higher doses of Dexketoprofen trometamol, but it had a slower onset. The 12.5-mg dose of Dexketoprofen trometamol was significantly superior to placebo but produced a lower level and shorter duration of analgesia compared to the other active treatments. There were no significant differences between 25 and 50 mg of Dexketoprofen trometamol in any measure of analgesic efficacy. No serious adverse events were observed and there were no significant differences in the incidence of adverse events among treatment groups. These results demonstrate that Dexketoprofen trometamol 25 mg is at least as effective as the racemic ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid onset of action compared to ketoprofen suggests that Dexketoprofen trometamol is more appropriate for treatment of acute pain.
Remei Artigas - One of the best experts on this subject based on the ideXlab platform.
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Single and repeated dose pharmacokinetics of Dexketoprofen trometamol in patients with impaired liver function.
Methods and Findings in Experimental and Clinical Pharmacology, 2006Co-Authors: J Valles, Remei Artigas, A Crea, F Muller, I Paredes, M Bertolotti, A CapriatiAbstract:: Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of Dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg Dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated Dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated Dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to 2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of Dexketoprofen trometamol in patients with impaired hepatic function is recommended.
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Comparison of Dexketoprofen Trometamol and Dipyrone in the Treatment of Renal Colic
Clinical Drug Investigation, 2003Co-Authors: Juan Sánchez-carpena, Monica Forns, Santiago Tomás-vecina, Javier Sesma-sánchez, Carlos Sánchez-juan, Dolors García-alonso, Jordi Rico-salvadó, Isabel Paredes, Remei ArtigasAbstract:Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for pain relief in patients with renal colic. Dexketoprofen trometamol is an NSAID that has demonstrated good analgesic efficacy and a good safety profile after oral administration in different models of acute and chronic pain. Objective: To assess the analgesic efficacy and safety of single intramuscular doses of Dexketoprofen trometamol (25 and 50mg) compared with dipyrone (2g) in moderate to severe pain due to renal colic. Study design: Multicentre, randomised, double-blind, parallel-group study. Patients: Patients of both sexes aged 18–70 years with a diagnosis of renal colic were eligible for randomisation if they presented with at least moderate pain as assessed by visual analogue scale (VAS) scoring ≥40mm on a scale of 100mm immediately before study drug administration. Methods: Assessment of analgesic efficacy was done using standard pain intensity and pain relief scales. Total scores from baseline to 6 hours after study drug administration were calculated for the sum of pain intensity differences relative to baseline (SPID), sum of analogue pain intensity differences relative to baseline (SAPID) and total pain relief scores (TOTPAR) as primary efficacy endpoints. Secondary efficacy and safety variables were also analysed. Results: A total of 333 patients (Dexketoprofen 25mg, n = 112; Dexketoprofen 50mg, n = 113; dipyrone 2g, n = 108) were included in the study. No significant differences were found between the treatment groups with regard to SPID (p = 0.797), SAPID (p = 0.852) and TOTPAR (p = 0.716). The time-effect course for pain intensity differences and pain relief showed significantly (p < 0.05) higher values for both doses of Dexketoprofen trometamol compared with dipyrone during the first hour after treatment administration. More than 90% of the patients in all three groups achieved pain relief of at least 50% as compared with baseline. Similarly, over 70% of the patients in all three groups considered the received treatment as excellent or good in the overall assessment of efficacy at the end of the study. No dose-effect relationship was observed in this pain model between both doses of Dexketoprofen trometamol. All three treatments were well tolerated, showing mostly mild to moderate adverse events. Conclusion: Dexketoprofen trometamol is a good analgesic for the treatment of moderate to severe pain due to renal colic, with a good safety profile and an efficacy comparable to that of dipyrone. The significantly greater effect of Dexketoprofen trometamol early after administration suggests a faster onset of action, which can be of paramount importance in this condition.
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pharmacokinetics of Dexketoprofen trometamol in healthy volunteers after single and repeated oral doses
The Journal of Clinical Pharmacology, 1998Co-Authors: Manel J Barbanoj, Ignasi Gich, Remei Artigas, Digna Tost, Cristina Moros, Rosa M Antonijoan, Luisa M Garcia, David MauleonAbstract:The pharmacokinetics of Dexketoprofen trometamol were evaluated in two studies using healthy volunteers. In the first study, the relative bioavailability of a single oral capsule of Dexketoprofen free acid 25 mg or Dexketoprofen trometamol 25 mg (given as 37 mg of the trometamol salt) was compared to ketoprofen 50 mg in 18 healthy volunteers. In the second study, the pharmacokinetics and tolerability of oral Dexketoprofen trometamol in tablet form were evaluated after either a single 25 mg dose (24 volunteers) or a repeated dose of 25 mg twice daily for 7 days (12 volunteers). The absorption of Dexketoprofen from Dexketoprofen trometamol capsules was bioequivalent to that of ketoprofen. On the other hand, the extent of absorption of Dexketoprofen free acid was significantly lower than that for ketoprofen. Dexketoprofen trometamol showed the most rapid absorption rate, with highest Cmax and shortest tmax values, whereas Dexketoprofen free acid had the slowest absorption rate, and ketoprofen had an intermediate absorption rate. After repeated-dose administration of Dexketoprofen trometamol, the pharmacokinetic parameters were similar to those obtained after single doses, indicating that no drug accumulation occurred. Dexketoprofen trometamol was well tolerated, with no clinically relevant adverse events reported.
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comparison of Dexketoprofen trometamol and ketoprofen in the treatment of osteoarthritis of the knee
The Journal of Clinical Pharmacology, 1998Co-Authors: Juan Beltran, Remei Artigas, E Martinmola, Manuel Figueroa, Josep Granados, Raimon Sanmarti, Ferran Torres, Monica Forns, David MauleonAbstract:: Dexketoprofen, the active enantiomer of the racemic compound ketoprofen, is a new nonsteroidal antiinflammatory drug (NSAID) of the arylpropionate family. The efficacy and safety of Dexketoprofen trometamol were compared with the equivalent enantiomeric dose of ketoprofen in a multicenter, randomized, double-blind 3-week trial of adult outpatients with pain due to osteoarthritis of the knee. After a washout period of 7-15 days, patients were randomly assigned to receive either Dexketoprofen trometamol 25 mg tid (N = 89) or ketoprofen 50 mg tid (N = 94). Of the 183 patients enrolled, two were lost to follow-up. At the end of treatment (3 weeks), the main efficacy outcome measures were significantly better in the Dexketoprofen trometamol group than in the ketoprofen group. In addition, overall physician assessment indicated that 75% of the Dexketoprofen group had improved compared with 50% of the ketoprofen patients. There were fewer adverse events in the Dexketoprofen treatment group, but the difference did not reach statistical significance. These results demonstrate that Dexketoprofen trometamol 25 mg tid is more effective than ketoprofen 50 mg tid in short-term symptomatic treatment of knee osteoarthritis and suggest that the tolerability of Dexketoprofen trometamol is more favorable than ketoprofen. Therefore, the substitution of Dexketoprofen for racemic ketoprofen may be advantageous in clinical practice.
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comparison of the efficacy and tolerability of Dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea
The Journal of Clinical Pharmacology, 1998Co-Authors: Miguel Ezcurdia, Remei Artigas, Ferran Torres, Francisco Javier Cortejoso, Ramon Lanzon, Francisco Javier Ugalde, Alfonso Herruzo, Francisca M Fernandez, David MauleonAbstract:: Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with Dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that Dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, Dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of Dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of Dexketoprofen or between Dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo.
Andrew R Moore - One of the best experts on this subject based on the ideXlab platform.
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single dose oral ketoprofen and Dexketoprofen for acute postoperative pain in adults
Cochrane Database of Systematic Reviews, 2017Co-Authors: Helen Gaskell, Sheena Derry, Philip J Wiffen, Andrew R MooreAbstract:Background Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically Dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and Dexketoprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and Dexketoprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared Dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis. Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 2.4 to 3.3. For dental studies only there was a trend to more efficacy at higher doses, with NNT decreasing from 2.4 at 12.5 mg to 1.6 at 100 mg. Dexketoprofen at doses of 10/12.5 mg and 20/25 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 3.2 and 3.6, with no obvious dose response. Significantly fewer participants used rescue medication with ketoprofen and Dexketoprofen than placebo. The median time to remedication was about 5 hours with ketoprofen and 4 hours with Dexketoprofen. The expected equivalent efficacy with a half dose of Dexketoprofen compared to ketoprofen was not demonstrated. Adverse events were uncommon with both drugs, and not significantly different from placebo. Authors' conclusions Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 3.3 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 at 50 mg dose). Duration of action is about 5 hours. Dexketoprofen is also effective with NNTs of 3.2 to 3.6 in the dose range 10 mg to 25 mg. Both drugs were well tolerated in single doses.
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Dexketoprofen tramadol randomised double blind trial and confirmation of empirical theory of combination analgesics in acute pain
Journal of Headache and Pain, 2015Co-Authors: Andrew R Moore, R. Figueiredo, T. Dietrich, S. Milleri, C. M. Hill, Cosme Gayescoda, Z Tothbagi, Daniel Torreslagares, Abel Garciagarcia, P. CoulthardAbstract:Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
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systematic review of Dexketoprofen in acute and chronic pain
BMC Clinical Pharmacology, 2008Co-Authors: Andrew R Moore, Jodie BardenAbstract:Background Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of Dexketoprofen in painful conditions to assess evidence on efficacy and harm.
P. Coulthard - One of the best experts on this subject based on the ideXlab platform.
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain
The Journal of Headache and Pain, 2015Co-Authors: R Andrew Moore, C. Gay-escoda, R. Figueiredo, Z. Tóth-bagi, T. Dietrich, S. Milleri, D. Torres-lagares, C. M. Hill, A. García-garcía, P. CoulthardAbstract:Background Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. Methods This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. Results 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Conclusions Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. Trial registration EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
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Dexketoprofen tramadol randomised double blind trial and confirmation of empirical theory of combination analgesics in acute pain
Journal of Headache and Pain, 2015Co-Authors: Andrew R Moore, R. Figueiredo, T. Dietrich, S. Milleri, C. M. Hill, Cosme Gayescoda, Z Tothbagi, Daniel Torreslagares, Abel Garciagarcia, P. CoulthardAbstract:Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain
Journal of Headache and Pain, 2015Co-Authors: R Andrew Moore, C. Gay-escoda, R. Figueiredo, Z. Tóth-bagi, T. Dietrich, S. Milleri, D. Torres-lagares, C. M. Hill, A. García-garcía, P. CoulthardAbstract:Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
R Andrew Moore - One of the best experts on this subject based on the ideXlab platform.
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain
Journal of Headache and Pain, 2015Co-Authors: R Andrew Moore, C. Gay-escoda, R. Figueiredo, Z. Tóth-bagi, T. Dietrich, S. Milleri, D. Torres-lagares, C. M. Hill, A. García-garcía, P. CoulthardAbstract:Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain
The Journal of Headache and Pain, 2015Co-Authors: R Andrew Moore, C. Gay-escoda, R. Figueiredo, Z. Tóth-bagi, T. Dietrich, S. Milleri, D. Torres-lagares, C. M. Hill, A. García-garcía, P. CoulthardAbstract:Background Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of Dexketoprofen and tramadol is untested, but predicted to be highly effective. Methods This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including Dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. Results 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the Dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to Dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. Conclusions Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. Trial registration EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).
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The Cochrane Library - Single dose oral ketoprofen and Dexketoprofen for acute postoperative pain in adults
Cochrane Database of Systematic Reviews, 2009Co-Authors: Helen Gaskell, Sheena Derry, Philip J Wiffen, R Andrew MooreAbstract:Background Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically Dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and Dexketoprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and Dexketoprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared Dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis. Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 2.4 to 3.3. For dental studies only there was a trend to more efficacy at higher doses, with NNT decreasing from 2.4 at 12.5 mg to 1.6 at 100 mg. Dexketoprofen at doses of 10/12.5 mg and 20/25 mg produced NNTs for at least 50% pain relief over 4 to 6 hours of 3.2 and 3.6, with no obvious dose response. Significantly fewer participants used rescue medication with ketoprofen and Dexketoprofen than placebo. The median time to remedication was about 5 hours with ketoprofen and 4 hours with Dexketoprofen. The expected equivalent efficacy with a half dose of Dexketoprofen compared to ketoprofen was not demonstrated. Adverse events were uncommon with both drugs, and not significantly different from placebo. Authors' conclusions Ketoprofen at doses of 25 mg to 100 mg is an effective analgesic in moderate to severe acute postoperative pain with an NNT for at least 50% pain relief of 3.3 with a 50 mg dose. This is similar to that of commonly used NSAIDs such as ibuprofen (NNT 2.5 for 400 mg dose) and diclofenac (NNT 2.7 at 50 mg dose). Duration of action is about 5 hours. Dexketoprofen is also effective with NNTs of 3.2 to 3.6 in the dose range 10 mg to 25 mg. Both drugs were well tolerated in single doses.