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1.
Clin Drug Investig ; 44(6): 413-424, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38842764

ABSTRACT

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Drug Combinations , Ketoprofen , Pyridoxine , Thiamine , Tromethamine , Vitamin B 12 , Humans , Double-Blind Method , Thiamine/administration & dosage , Thiamine/analogs & derivatives , Thiamine/therapeutic use , Ketoprofen/administration & dosage , Ketoprofen/analogs & derivatives , Female , Adult , Pyridoxine/administration & dosage , Pyridoxine/therapeutic use , Male , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Vitamin B 12/analogs & derivatives , Vitamin B 12/administration & dosage , Vitamin B 12/therapeutic use , Middle Aged , Tromethamine/administration & dosage , Prospective Studies , Vitamin B Complex/administration & dosage , Vitamin B Complex/therapeutic use , Pain Measurement/methods , Young Adult
3.
Ann Med ; 56(1): 2357235, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38813682

ABSTRACT

OBJECTIVE: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults. METHODS: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554. RESULTS: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I2 between the studies was low. CONCLUSIONS: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).


To our knowledge, this is the first network meta-analysis comparing the available data on adult patients with episodic tension-type headache (ETTH) treated with different simple analgesics recommended by the current guidelines.Ibuprofen (400 mg) and diclofenac-K (12.5 mg, 25 mg) are potentially the most effective and safe treatment options, supported by high-quality evidence.


Subject(s)
Analgesics , Ibuprofen , Network Meta-Analysis , Tension-Type Headache , Humans , Tension-Type Headache/drug therapy , Analgesics/adverse effects , Analgesics/therapeutic use , Analgesics/administration & dosage , Adult , Ibuprofen/adverse effects , Ibuprofen/administration & dosage , Ibuprofen/therapeutic use , Acetaminophen/therapeutic use , Acetaminophen/adverse effects , Acetaminophen/administration & dosage , Bayes Theorem , Treatment Outcome , Diclofenac/adverse effects , Diclofenac/therapeutic use , Diclofenac/administration & dosage , Randomized Controlled Trials as Topic , Naproxen/therapeutic use , Naproxen/adverse effects , Naproxen/administration & dosage , Ketoprofen/adverse effects , Ketoprofen/therapeutic use , Ketoprofen/administration & dosage , Ketoprofen/analogs & derivatives , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Female , Male
4.
Eur J Trauma Emerg Surg ; 50(4): 1791-1798, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38653816

ABSTRACT

INTRODUCTION: Long bone fractures (LBF) often cause severe pain, impacting patients' quality of life. This prospective, randomized, double-blind study aimed to compare the analgesic efficacy of dexketoprofen (Dex) and ibuprofen (Ibu) in LBF patients in the emergency department. METHODS: Conducted between August 10, 2023, and January 17, 2024, the study included 100 eligible patients randomized into Dex and Ibu groups. Visual analog scale (VAS) scores were measured at baseline and at 30, 60, and 120 min. DeltaVAS (ΔVAS) values and ΔVAS percentages (ΔVAS%) were calculated. Primary endpoints were ΔVAS scores (ΔVAS 30-60-120) and ΔVAS% for comparative analysis. RESULTS: Statistical analysis showed no significant difference in ΔVAS30 (p = 0.359). However, ΔVAS60 exhibited a significant difference (p = 0.027), as did ΔVAS120 (p = < 0.001). ΔVAS%30 showed no significance (p = 0.224), but ΔVAS%60 and ΔVAS%120 were clinically and statistically significant (p = 0.017 and p = < 0.001, respectively). CONCLUSION: Ibuprofen 800 mg demonstrated superior analgesic efficacy at 60 and 120 min compared to Dex in long bone fractures. These findings suggest ibuprofen's potential as an effective pain management option in emergency departments.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Fractures, Bone , Ibuprofen , Ketoprofen , Pain Measurement , Humans , Ibuprofen/therapeutic use , Double-Blind Method , Ketoprofen/analogs & derivatives , Ketoprofen/therapeutic use , Ketoprofen/administration & dosage , Male , Female , Prospective Studies , Middle Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Adult , Fractures, Bone/complications , Tromethamine/therapeutic use , Tromethamine/administration & dosage , Pain Management/methods , Aged , Emergency Service, Hospital
5.
BMJ Open ; 14(3): e080620, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38508619

ABSTRACT

INTRODUCTION: Satisfactory management of acute pain remains a major medical challenge despite the availability of multiple therapeutic options including the fixed-dose combination (FDC) drugs. Tramadol and dexketoprofen trometamol (TRAM/DKP) 75/25 mg FDC was launched in 2018 in Asia and is widely used in the management of moderate to severe acute pain. There are limited data on its effectiveness and safety in Asian patients, and therefore, a need to better understand its usage patterns in clinical practice. We aim to understand the usage pattern of TRAM/DKP FDC, its effectiveness and tolerability in patients with moderate to severe acute pain in Asia. METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app. ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.


Subject(s)
Acute Pain , Ketoprofen/analogs & derivatives , Tramadol , Tromethamine , Humans , Male , Female , Tramadol/therapeutic use , Acute Pain/drug therapy , Prospective Studies , Pain, Postoperative/drug therapy , Double-Blind Method , Registries , Thailand , Observational Studies as Topic , Drug Combinations
6.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473945

ABSTRACT

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors' knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode.


Subject(s)
Amylose , Chromatography, Reverse-Phase , Ketoprofen/analogs & derivatives , Tromethamine , Amylose/chemistry , Temperature , Polysaccharides/chemistry , Cellulose/chemistry , Chromatography, High Pressure Liquid/methods , Water , Acetonitriles , Stereoisomerism
7.
J Coll Physicians Surg Pak ; 34(2): 160-165, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38342865

ABSTRACT

OBJECTIVE: To evaluate the analgaesic efficacy of tenoxicam and dexketoprofen in patients admitted to the Emergency Medicine (EM) Clinic with severe acute pain due to primary dysmenorrhea (PD). STUDY DESIGN: Randomised-controlled trial. Place and Duration of the Study: Emergency Medicine Clinic, Health Sciences University, Adana City Training and Research Hospital, Adana, Turkiye, from January to December 2022. METHODOLOGY: Patients presenting with PD, were divided into two groups of 60 each, administered 50 mg dexketoprofen and 20 mg tenoxicam intravenously. Visual analogue scale (VAS) scores were recorded at the 15th, 30th, 60th, and 120th minutes. VAS scores and ΔVAS scores were compared with the effectiveness of drugs, the need for rescue drugs and its side-effects. RESULTS: Intravenous (IV) dexketoprofen was administered to 60 of the patients and IV tenoxicam was administered to another 60. At the time of admission, mean VAS scores of the patients were 8.8 ± 0.9 for the dexketoprofen group and 8.6 ± 0.8 for the tenoxicam group. The VAS scores of the dexketoprofen group were found to be statistically significantly lower after 30 minutes with lower need for rescue analgaesics. ΔVAS scores of the dexketoprofen group were statistically significantly higher from the 30th minute. CONCLUSION: According to the VAS scoring, IV dexketoprofen was a more effective drug than IV tenoxicam in patients who were admitted to the EM clinic with severe pain due to PD. KEY WORDS: Dexketoprofen, Primary dysmenorrhea, VAS score.


Subject(s)
Acute Pain , Anti-Inflammatory Agents, Non-Steroidal , Ketoprofen , Piroxicam , Tromethamine , Female , Humans , Acute Pain/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Double-Blind Method , Dysmenorrhea/drug therapy , Ketoprofen/analogs & derivatives , Pain, Postoperative/drug therapy , Piroxicam/analogs & derivatives
8.
Curr Drug Metab ; 25(1): 63-70, 2024.
Article in English | MEDLINE | ID: mdl-38258775

ABSTRACT

BACKGROUND: The simultaneous use of NSAIDs and antibiotics is recommended for bacterial diseases in human and veterinary medicine. Moxifloxacin (MFX) and dexketoprofen (DEX) can be used simultaneously in bacterial infections. However, there are no studies on how the simultaneous use of DEX affects the pharmacokinetics of MFX in rats. OBJECTIVES: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics of MFX in male and female rats. METHODS: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the highperformance liquid chromatography-UV and pharmacokinetic parameters were evaluated by noncompartmental analysis. RESULTS: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to 8 h (AUC0-8) and peak concentration (Cmax) of MFX in rats, while it significantly decreased the total body clearance (CL/F). When female and male rats were compared, significant differences were detected in AUC0-8, Cmax, CL/F and volume of distribution. The AUC0-8lung/AUC0-8plasma ratios of MFX were calculated as 1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively. CONCLUSION: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats but did not change its passage to the lung. However, there is a need for a more detailed investigation of the difference in the pharmacokinetics of MFX in male and female rats.


Subject(s)
Ketoprofen , Lung , Moxifloxacin , Rats, Sprague-Dawley , Animals , Female , Male , Moxifloxacin/pharmacokinetics , Ketoprofen/pharmacokinetics , Ketoprofen/administration & dosage , Ketoprofen/analogs & derivatives , Rats , Lung/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Drug Interactions , Tromethamine/pharmacokinetics , Tissue Distribution
9.
Hip Int ; 34(3): 304-310, 2024 May.
Article in English | MEDLINE | ID: mdl-38204364

ABSTRACT

BACKGROUND: Multimodal analgesia for total hip arthroplasty (THA) is increasingly employed to reduce early postoperative pain and promote fast patient discharge. The aim of this study was to compare the efficacy and tolerability of tramadol/dexketoprofen (TRAM/DKP, Group A) versus paracetamol + tramadol (PARA+TRAM, Group B) in patients undergoing THA using minimally invasive direct anterior approach (DAA). METHODS: A single-centre, randomised, single-blind, parallel, interventional study conducted in 323 patients undergoing primary THA with DAA was performed. Group A consisted of 188 patients and Group B of 135. The primary endpoints were the change from baseline (measured 2 hours postoperatively) in pain intensity (PI) during the treatment period (48 hours), assessed by visual analogue scale (VAS) at pre-specified postoperative time-points (2, 8, 24, 48 hours) and the total rescue medication (RM) use during the first 24 hours postoperatively. RESULTS: As early as 2 hours after baseline, Group A showed a greater PI reduction from baseline compared to Group B (-26.24% vs. -6.87%; p < 0.001). A lower mean PI (VAS) score was consistently found over the entire observation period following treatment with TRAM/DKP than with PARA+TRAM as well as more than 2-fold higher proportion of responders at the end of treatment period. More patients in Group B required RM in comparison to those in Group A (15.6% vs. 3.7%, p < 0.001). Both treatments were well tolerated. CONCLUSIONS: After THA, oral TRAM/DKP provides faster and greater pain relief when compared to intravenous PARA+TRAM with limited consumption of RM and favourable tolerability profile. Our study expands the use of TRAM/DKP in the setting of major orthopaedic surgeries. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT04178109).


Subject(s)
Acetaminophen , Analgesics, Opioid , Arthroplasty, Replacement, Hip , Ketoprofen , Ketoprofen/analogs & derivatives , Pain Measurement , Pain, Postoperative , Tramadol , Tromethamine , Humans , Pain, Postoperative/drug therapy , Pain, Postoperative/diagnosis , Male , Female , Tramadol/administration & dosage , Tramadol/therapeutic use , Acetaminophen/administration & dosage , Acetaminophen/therapeutic use , Middle Aged , Ketoprofen/administration & dosage , Ketoprofen/therapeutic use , Single-Blind Method , Aged , Administration, Oral , Tromethamine/administration & dosage , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Treatment Outcome , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Drug Therapy, Combination , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Adult , Pain Management/methods
10.
Eur J Clin Pharmacol ; 80(3): 475-480, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38245872

ABSTRACT

PURPOSE: Opioids are widely used to treat painful vaso-occlusive crises (VOC) in sickle cell disease (SCD). However, due to opioids' significant adverse effect profiles, the search for alternative therapies continues from the past to the present. The study aimed to investigate the efficacy of acetaminophen and dexketoprofen in the treatment of painful VOC. METHODS: This study is a single-center, prospective, non-randomized, single-blinded, controlled study. The study comprised two groups: the first administered acetaminophen and dexketoprofen mixed group, while the second received them sequential group. Opioids were used in patients with persistent pain despite these analgesics. Demographic and laboratory information, pain scores, opioid requirement, dose amount, side effects, and length of hospital stay of the patients were recorded. RESULTS: The study comprised 56 (100%) patients with painful VOC, 29 (51.8%) from the mixed group, and 27 (48.2%) from the sequential group. Opioid use was seen in 16 (55.2%) patients in the mixed group and 21 (77.8%) patients in the sequential group (p = 0.074). The median amount of opioid used was significantly lower in the mixed group than in the sequential group (p < 0.001). Also, the median length of hospital stay was significantly lower in the mixed group than in the sequential group (p < 0.001). CONCLUSION: Our study suggests that administering acetaminophen and dexketoprofen in the mix for the treatment of painful VOC in patients with SCD may be a more efficient approach compared to sequential administration. This approach appears to reduce opioid usage and shorten hospital stays.


Subject(s)
Anemia, Sickle Cell , Ketoprofen/analogs & derivatives , Tromethamine , Volatile Organic Compounds , Humans , Acetaminophen/therapeutic use , Analgesics, Opioid/therapeutic use , Prospective Studies , Volatile Organic Compounds/therapeutic use , Pain/drug therapy , Anemia, Sickle Cell/drug therapy
11.
Drug Test Anal ; 16(3): 289-302, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37439283

ABSTRACT

Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post-drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3-hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3-hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vdss was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (-) ketoprofen, respectively. The mean half-life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (-) ketoprofen. Stimulation of ketoprofen-treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2 , PGE2 , PGF2alpha , LTB4 , and 15(s)-HETE production for up to 120 h post-drug administration.


Subject(s)
Ketoprofen , Ketoprofen/analogs & derivatives , Horses , Animals , Ketoprofen/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal , Chromatography, Liquid , Calcium Ionophores , Lipopolysaccharides , Tandem Mass Spectrometry , Eicosanoids , Biomarkers
12.
Arch Esp Urol ; 75(7): 624-629, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36214144

ABSTRACT

OBJECTIVES: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. RESULTS: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. CONCLUSIONS: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.


Subject(s)
Lithiasis , Lithotripsy , Music , Analgesics , Fentanyl/therapeutic use , Humans , Ketoprofen/analogs & derivatives , Lithiasis/complications , Lithiasis/drug therapy , Lithotripsy/methods , Midazolam/therapeutic use , Nitrous Oxide/therapeutic use , Pain/etiology , Pain/prevention & control , Prospective Studies , Tromethamine
13.
Biomed Pharmacother ; 153: 113336, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35772374

ABSTRACT

Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the incidence of NSAID-associated adverse events has increased exponentially over the past decades. Ketoprofen (ketoprofen acid, KA) is a widely used NSAID and, like with other NSAIDs, its use can be associated with adverse effects that especially involve the gastrointestinal tract and the kidney. The salification of KA with L-lysine has led to the synthesis of ketoprofen lysine salt (KLS), which is characterized by higher solubility and a more rapid gastrointestinal absorption compared to KA. Previous studies have reported that KLS has also an increased gastric tolerance in vitro, and this is due to the inhibition of lipid peroxidation and reactive oxygen species scavenging effects of L-lysine. Here, we report in vivo tolerability/toxicity studies that were conducted prior seeking KLS marketing authorization, in which we compared KLS and KA safety profile, focusing in particular on the evaluation of the gastrointestinal and renal tolerability of the drugs administered orally to dogs. Our results demonstrate that KLS has an increased in vivo gastrointestinal tolerability compared to KA and show, for the first time, that KLS has also increased in vivo renal tolerability compared to KA, thus supporting the concept that L-lysine may counteract NSAID-induced oxidative stress-mediated gastrointestinal and renal injury.


Subject(s)
Ketoprofen , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Dogs , Ketoprofen/analogs & derivatives , Kidney , Lysine/analogs & derivatives , Lysine/pharmacology , Stomach
14.
Am J Emerg Med ; 56: 223-227, 2022 06.
Article in English | MEDLINE | ID: mdl-35461026

ABSTRACT

INTRODUCTION: Non-traumatic back pain constitutes roughly 5% of the admissions to emergency departments. This study seeks to compare the efficacy of intravenously administered paracetamol, dexketoprofen, and ibuprofen in patients with non-traumatic acute low back pain. METHODS: This study was designed as a randomized, double-blinded investigation and carried out at a tertiary hospital. 210 eligible patients without trauma who presented with low back pain were recruited for the study and randomized into paracetamol (n = 71), dexketoprofen (n = 70), and ibuprofen (n = 69) groups. The measurements at 0, 15, 30 and 60 min were noted down by using a 100 mm VAS, and the relevant comparisons were made. RESULTS: The VAS scores at 0 and 60 min in the paracetamol, dexketoprofen, and ibuprofen groups decreased on average by 40 mm, 42 mm, and 43 mm, respectively. The baseline and final pain scores of each drug group differed significantly (p < 0.05), though the between-group analysis revealed no significant difference (p > 0.05). CONCLUSION: Given the obtained data, we did not note a significant difference between intravenous paracetamol, dexketoprofen and ibuprofen with respect to pain efficacy in non-traumatic acute low back pain. Based on the patients' clinical conditions and histories, we concluded that the choice of medication might not change the efficacy of the treatment and patient comfort.


Subject(s)
Acute Pain , Analgesics, Non-Narcotic , Low Back Pain , Acetaminophen/therapeutic use , Acute Pain/drug therapy , Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Double-Blind Method , Humans , Ibuprofen/therapeutic use , Ketoprofen/analogs & derivatives , Low Back Pain/drug therapy , Tromethamine
15.
Biomed Pharmacother ; 149: 112819, 2022 May.
Article in English | MEDLINE | ID: mdl-35299123

ABSTRACT

Dexketoprofen is an enantiomer of ketoprofen (S+) that belongs to nonsteroidal anti-inflammatory drugs and has analgesic, anti-inflammatory, and antipyretic properties. Dexketoprofen has a stronger effect than ketoprofen, which makes it a readily used preparation. The review aims to find in recent original publications data about dexketoprofen and its comparison with other painkilling medications. The systematic literature review was conducted in November 2021 (2018 onwards). We selected 12 articles from PubMed, Google Scholar, Medline Complete databases. In the last 4 years, there have been many publications that shed a new light on dexketoprofen. The article is a comparative analysis of dexketoprofen's action vs other nonsteroidal anti-inflammatory drugs and the combination of dexketoprofen with tramadol vs paracetamol with tramadol. The findings of the review confirm that dexketoprofen is a very good pain reliever more potent than paracetamol. Dexketoprofen produces similar effects to lidocaine and dexmedetomidine. Complex preparations containing dexketoprofen and tramadol are very effective painkilling tandem and are more effective than tramadol and paracetamol therapy in the treatment of acute pain.


Subject(s)
Ketoprofen , Tramadol , Acetaminophen , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ketoprofen/analogs & derivatives , Ketoprofen/pharmacology , Ketoprofen/therapeutic use , Tromethamine/therapeutic use
16.
Eur J Clin Pharmacol ; 78(1): 27-33, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34528122

ABSTRACT

PURPOSE: Although different forms of lidocaine are used for migraine attack headaches, the effect of intravenous lidocaine is still limited. This study aimed to investigate the effects of intravenous lidocaine infusion for the treatment of migraine attack headaches. METHODS: A hundred patients with migraine attacks, aged between 18 and 65, were randomly divided into two groups. The lidocaine group (n = 50) received a 1.5 mg/kg lidocaine bolus and a 1 mg/kg infusion (first 30 min), followed by a 0.5 mg/kg infusion for a further 30 min intravenously. The non-steroidal anti-inflammatory drug (NSAID) group (n = 50) received 50 mg dexketoprofen trometamol and saline at the same volume as the lidocaine at the same time intervals intravenously. The Visual Analog Scale (VAS) pain scores, additional analgesia requirement, side effects, and revisits to the emergency department were recorded. RESULTS: The VAS score was significantly lower in the lidocaine group than in the NSAID group for the first 20th and 30th minutes (p = 0.014 and p = 0.024, respectively). There was no difference between the VAS scores for the remaining evaluation times (p > 0.05). In terms of secondary outcomes, rescue medication requirement was not different between the two groups at both the 60th and 90th minutes (p > 0.05). However, the number of patients revisiting ED within 48-72 h was statistically less in the lidocaine group than in the NSAID group (1/50 vs. 8/50; p = 0.031). CONCLUSION: Intravenous lidocaine may be an alternative treatment method for patients with migraine attack headaches in the emergency department.


Subject(s)
Anesthetics, Local/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ketoprofen/analogs & derivatives , Lidocaine/therapeutic use , Migraine Disorders/drug therapy , Tromethamine/therapeutic use , Adult , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Double-Blind Method , Female , Humans , Infusions, Intravenous , Ketoprofen/administration & dosage , Ketoprofen/adverse effects , Ketoprofen/therapeutic use , Lidocaine/administration & dosage , Lidocaine/adverse effects , Male , Middle Aged , Pain Measurement , Prospective Studies , Tromethamine/administration & dosage , Tromethamine/adverse effects
17.
Braz J Anesthesiol ; 72(3): 365-371, 2022.
Article in English | MEDLINE | ID: mdl-34411625

ABSTRACT

OBJECTIVE: Ischemia/reperfusion (I/R) may cause irreversible damage to tissues and organs. We evaluated the effects of dexketoprofen on a renal I/R model in rats. METHODS: The study included 30 male rats. Control group received 1 mL of saline. Dexketoprofen group received 1 mL (25 mg) of dexketoprofen intraperitoneally. After 60 minutes renal ischemia, 23 hours reperfusion was applied. In Sham group, laparotomy was performed with a medial line incision without any additional procedure. Changes in the plasma malondialdehyde (MDA), renal tissue MDA, plasma glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), BUN, creatinine and albumin levels, and histopathological changes were evaluated. RESULTS: CAT values were significantly lower in Control as compared with the Sham group. Plasma levels of MDA in the Control group were significantly higher than in the Dexketoprofen group. BUN and creatinine values were significantly higher in the Dexketoprofen group. The severity of tissue injury in the Dexketoprofen group was significantly higher than in Control and Sham groups CONCLUSION: Although dexketoprofen reduces the I/R-induced systemic inflammation, it increases renal tissue damage.


Subject(s)
Reperfusion Injury , Animals , Creatinine/pharmacology , Humans , Ketoprofen/analogs & derivatives , Kidney , Male , Malondialdehyde , Rats , Rats, Wistar , Reperfusion Injury/prevention & control , Tromethamine
18.
J Evid Based Dent Pract ; 21(4): 101618, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34922724

ABSTRACT

OBJECTIVE: Impacted third molar extraction is associated with acute moderate-to-severe pain for up to 48 hours post-surgery. This trial was designed to compare the analgesic effectiveness, swelling, and adverse events after impacted third molar surgery following multimodal therapy with 75 mg tramadol hydrochloride plus 25 mg dexketoprofen or monotherapy with 400 mg ibuprofen. METHODS: Seventy-two patients were randomly assigned to receiving ibuprofen (n = 36) or tramadol-dexketoprofen (n = 36). Postoperative pain intensity and swelling were measured using a visual analog scale (VAS); pain relief experienced was reported using a 4-point verbal rating scale; the rescue medication requirement, adverse effects, and global impression of the medication were recorded. RESULTS: No statistically significant between-group difference in pain intensity was observed at any time point; however, pain relief was significantly higher in the tramadol-dexketoprofen treated-group at 6 and 36 hours. Self-reported verbal rating scale assessments showed significantly lower swelling in the tramadol-dexketoprofen group at 24 hours post-surgery but not at 48 or 72 hours, and VAS-swelling scores showed no significant between-group difference. The frequency of postoperative nausea and dizziness was significantly higher in the tramadol-dexketoprofen group. CONCLUSIONS: Multimodal therapy proved more effective to manage moderate-severe pain after impacted third molar surgery in comparison to monotherapy. However, the improvement in relief must be balanced against the increased risk of adverse effects when considering this multimodal approach.


Subject(s)
Tramadol , Analgesics , Double-Blind Method , Drug Combinations , Humans , Ibuprofen/therapeutic use , Ketoprofen/analogs & derivatives , Molar, Third/surgery , Pain, Postoperative/drug therapy , Tooth Extraction , Tramadol/therapeutic use , Tromethamine
19.
Epilepsy Res ; 178: 106827, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34847424

ABSTRACT

AIM: Dexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats. METHOD: In this study, 28 male Wistar rats weighing 220-240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats' left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG). RESULTS: The low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05). CONCLUSION: This study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures.


Subject(s)
Penicillins , Seizures , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Ketoprofen/analogs & derivatives , Male , Penicillins/toxicity , Rats , Rats, Wistar , Seizures/chemically induced , Seizures/drug therapy , Tromethamine/therapeutic use
20.
Biomed Pharmacother ; 141: 111938, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34328086

ABSTRACT

INTRODUCTION: Ketoprofen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Side effects of ketoprofen occur mainly from the gastrointestinal tract due to the inhibition of cyclooxygenaze-1. Binge drinking at least once a week is reported by 80 million Europeans. On the day after many of them use NSAIDs. This increases the risk for damage of gastric mucosa. AIM: The aim of the study was to check if use of ketoprofen lysine salt (KLS) has any gastroprotective effect on mucosa of rat stomach after ethyl alcohol intoxication. MATERIALS AND METHODS: There were 6 groups of 6 male rats which received: RESULTS: In groups 1, 2 and 3 the histopathologic examination of the stomachs revealed normal picture, without signs of inflammation. In the group 4, 5 and 6 within the mucosa and submucosa there were visible numerous infiltrates of inflammatory cells, consisting mainly of lymphocytes, plasmocytes and eosinophilia. Total leukocyte count was elevated in group 3, 4, 6. There was a significant decrease of blood urea concentration in group 6 vs 2 and significant decrease of serum albumin in group 6 vs 1 and 2, and total protein vs group 1. CONCLUSION: Side effects of ketoprofen occur mainly from the gastrointestinal tract. KLS has no gastroprotective effect after ethanol-gastric injury and does not protect gastric mucosa from damage produced by binge drinking. Therefore it should not be used after drinking distilled spirits.


Subject(s)
Alcoholic Intoxication/pathology , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Ethanol/toxicity , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Ketoprofen/analogs & derivatives , Lysine/analogs & derivatives , Alcoholic Intoxication/drug therapy , Alcoholic Intoxication/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cyclooxygenase 1/metabolism , Gastric Mucosa/metabolism , Ketoprofen/administration & dosage , Ketoprofen/toxicity , Lysine/administration & dosage , Lysine/toxicity , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/metabolism , Rats , Rats, Wistar
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