The effectiveness of intradermal sterile water injection for low back pain in the emergency department: A prospective, randomized controlled study.

AIM: Low back pain (LBP) is a common musculoskeletal complaint among emergency department (ED) admissions. In this study, it was aimed to compare the effectiveness of systemic treatment with intradermal sterile water injection (ISWI) treatment protocol combined with systemic therapy in patients with LBP of unclear chronicity. METHODS: A prospective randomized, unblinded, controlled clinical study was conducted on patients admitted to the ED for LBP of unclear chronicity. One hundred twelve patients were randomly assigned to two groups; Group ISWI (n = 56) administered ISWI in the LBP region of patients along with systemic intravenous dexketoprofen therapy, while the other group (n = 56) received only systemic intravenous dexketoprofen therapy. The treatment methods' effectiveness was compared by measuring the pain intensity with the Visual Analog Scale (VAS) at admission, 10th minutes, 20th minutes, 30th minutes, and 24 h later. Also, opioid and analgesic consumptions in 24 h after treatment and patient satisfactions were compared. RESULTS: In the treatment of LBP, ISWI treatment was found to be more effective in relieving pain than systemic therapy alone (p < 0.001). Also, it was observed that opioid consumption in the ED and analgesic consumption within 24 h after treatments were decreased in the ISWI group (p < 0.001). The patient satisfaction in the ED was statistically increased (p < 0.001). DISCUSSION: In this unblinded study, ISWI with systemic therapy improved pain outcomes more than systemic therapy alone. Further research is needed to determine whether this was due entirely to placebo effect.

Diets with no or low amounts of dietary fiber can reduce small intestinal ulcers induced by non-steroidal anti-inflammatory drugs in dogs.

Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o.), ketoprofen (2 mg/kg, s.c.), or fulnixin (1 mg/kg, s.c.) was administered once daily at 10 a.m. after a morning meal or without a morning meal (fasted condition) for 3 - 7 days. Gastrointestinal lesions were examined 24 h after the final dose of the drugs. When indomethacin (3 mg/kg) was administered after a morning meal (fed condition) for 7 days, it produced many lesions in the small intestine. However, when it was given in the fasted condition without the morning meal, the lesions were markedly decreased. All the NSAIDs given after feeding of regular dry food containing 6% DF once a day for 3 days produced many lesions in the small intestine. The lesions were decreased or increased in dogs given prescription diets containing low DF (1.1%) and high DF (15.4%), respectively. Furthermore, lesions were not observed in dogs given canned diet containing very low DF (< 0.1%), whereas lesions appeared again in dogs given canned diet supplemented with cellulose (3 or 10%) but not with pectin (10%). These results suggested that both feeding condition and insoluble DF, such as cellulose in the diet, play an important role in the formation of NSAID-induced small intestinal lesions, and that a diet with no or low amounts of DF may decrease gastrointestinal side-effects associated with the use of NSAIDs.

Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property.

This study investigates anti-inflammatory activity with improved pharmacokinetic and non-ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation-induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti-inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non-ulcerogenic potential of ester prodrugs of ketoprofen.

[Nonspecific low-back pain: from symptomatic treatment to pathogenesis-based treatment].

OBJECTIVE: To study the efficacy and safety of artrosilene in the combination with piascledine in patients with low-back pain. METHODS: Sixty patients, 42 women and 18 men (mean age 53,6±10,4 years) with chronic nonspecific low-back pain were treated with artrosilene (ketoprofen lysine salt) in the combination with the chondro protector piascledine (a mix of avocado and soybean oil extracts). RESULTS: There the persistent decrease in the intensity of pain syndrome and severity of vertebral syndrome and improvement of quality of life. CONCLUSIONS: The drugs can be recommended for treatment of nonspecific low-back pain.

Development of a novel ketoprofen transdermal patch: effect of almond oil as penetration enhancers on in-vitro and ex-vivo penetration of ketoprofen through rabbit skin.

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.

Comparison of acute toxicity of ketoprofen to juvenile and embryonic stages of Danio rerio.

OBJECTIVES: Ketoprofen is a common human medicine from a class of non-steroidal anti-inflammatory drugs (NSAIDs), which is provably detected in surface waters in concentrations ordinarily in µg.L-1. The aim of this study was to compare the acute toxicity of ketoprofen to embryonic and juvenile stages of aquarium fish - zebrafish (Danio rerio). METHODS: Tests were performed according to the methods of the Organisation for Economic Co-operation and Development (OECD) No. 203 (Fish, acute toxicity test) and OECD No. 212 (Fish, short-term toxicity test on embryo and sac-fry stages). RESULTS: The results showed (mean ± SD) LC50 value of ketoprofen to be 632.30 ± 10.10 mg.L-1 in juvenile zebrafish and 6.44 ± 2.22 mg.L-1 in embryonic stages of zebrafish. The results revealed statistically significantly higher sensitivity (p<0.01) of the embryonic stages of zebrafish to ketoprofen compared to its juveniles. The susceptibility of embryos depends on many factors, especially yet improperly developed enzymatic system in embryos, different ways of the absorption of the substance into the organism or differences in metabolism pathways. CONCLUSIONS: The acute toxicity of ketoprofen for juvenile stages of zebrafish is low, but the substance seems to be toxic for embryonic stages.

Effects of combination treatment with ketoprofen 100 mg + acetaminophen 1000 mg on postoperative dental pain: a single-dose, 10-hour, randomized, double-blind, active- and placebo-controlled clinical trial.

BACKGROUND: A combination of analgesic drugs with different pharmacologic properties may be more effective, with fewer adverse events, than either agent used alone. OBJECTIVE: This study assessed whether the combination of acetaminophen and ketoprofen is more effective and better tolerated than either drug used alone in treating postoperative pain. METHODS: This single-dose randomized, double-blind, active- and placebo-controlled study was conducted at the Finnish Student Health Service, Oulu, Finland. Patients aged 18 to 40 years with moderate or severe pain (>or=3 on a numerical rating scale [NRS] of 0-10) after surgical removal of impacted third molars were randomly assigned to receive one of the following drugs in single oral doses: ketoprofen 100 mg + acetaminophen 1000 mg, ketoprofen 100 mg, acetaminophen 1000 mg, or placebo tablets. Effectiveness was assessed by the onset of analgesia, pain intensity difference (PID) from baseline, sum of PID (SPID), and duration of analgesic effect. Patients rated pain intensity on the NRS at rest and on dry swallowing. Onset of pain relief was measured using time to PID in >or=1 category at rest or on dry swallowing (PID >or=1). Patients recorded the occurrence of adverse events and the supplemental consumption of rescue medication (ibuprofen). RESULTS: The study included 76 patients, accounting for 78 cases (2 patients were operated on twice and were assessed as 4 individual patients) (59% women, 41% men; mean age, 22.8 years; white race, 100%; and mean weight, 68.3 kg). At 1.5 hours, mean SPIDs at rest and on swallowing were significantly greater in the combination group than in the acetaminophen, ketoprofen, and placebo groups (all, P < 0.05). Mean time to onset of pain relief (PID >or=1) at rest and on swallowing were significantly less in the combination group than the acetaminophen, ketoprofen, and placebo groups (all, P < 0.05). Median time to use of rescue medication was significantly longer in the combination group than in the acetaminophen group (P = 0.006) and the placebo group (P < 0.001) but not the ketoprofen group. At 1.5 hours after administration, maximum sedation scores were not significantly different between the study groups. The prevalences of trismus, bleeding, and edema were not significantly different between the study groups. CONCLUSIONS: The results from this study suggest that the combination of ketoprofen 100 mg + acetaminophen 1000 mg provided a significantly more rapid onset of analgesia than either drug given alone in the management of pain after oral surgery in this patient population. Adverse events were not significantly different between the study groups. These results support the clinical practice of combining ketoprofen with acetaminophen for the management of acute pain.

Efficacy of oral rofecoxib versus intravenous ketoprofen as an adjuvant to PCA morphine after urologic surgery.

BACKGROUND: Adjunctive use of nonsteroidal anti-inflammatory drugs has become increasingly popular in the perioperative period because of their opioid-sparing effects. This randomized, controlled, double-dummy study was designed to evaluate the cost-effectiveness of using oral rofecoxib as an alternative to intravenous ketoprofen for pain management in patients undergoing urologic surgery. METHODS: Seventy patients were randomly assigned to receive either a placebo (Control) or rofecoxib 50 mg po (Rofecoxib) 1 h prior to surgery. After a standardized spinal anesthetic, patients in the Control group received ketoprofen 100 mg IV q 8 h for 24 h, while the Rofecoxib group received an equivolume of saline at 8-h intervals for 24 h. Both groups were allowed to self-administer morphine (1 mg IV boluses) using a PCA delivery system. The need for 'rescue' analgesic medication, as well as pain scores [using an 11-point verbal rating scale (VRS) (0 = none to 10-severe)], were recorded at 1, 2, 6, 12, and 24-h intervals after surgery. In addition, the incidences of side-effects were recorded at the end of the study period. RESULTS: Total amount of morphine required in the initial 24-h postoperative period was nonsignificantly reduced in the Rofecoxib group (29 +/- 2 vs. 37 +/- 4 mg). More importantly, the percentage of patients reporting moderate-to-severe pain (VRS score > or =4) during the study period was lower in the Rofecoxib group (12 vs. 22%, P < 0.05). The daily cost of rofecoxib (USD 1.14 for 50-mg dose) was also significantly less than ketoprofen (USD 3.06 for three 100-mg doses). CONCLUSION: Premedication with oral rofecoxib (50 mg) is a cost-effective alternative to the parenteral nonselective NSAID, ketoprofen (100 mg q 8 h), when used as an adjuvant to PCA morphine for pain management after urologic surgery.

[Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats]. / Dexketoprofeno. Aine preferencial inhibidor COX-1, sin lesión gastrointestinal, en ratas.

Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition.

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty.

BACKGROUND: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty. METHODS: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone. RESULTS: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss. CONCLUSION: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not.

Comparison of parenteral diclofenac and ketoprofen for postoperative pain relief after maxillofacial surgery.

Non-steroidal anti-inflammatory drugs (NSAID) effectively reduce the need for opioid analgesia after various types of surgery. The efficacy of diclofenac and ketoprofen to relieve pain after maxillofacial surgery was compared in the present study. In a randomized and double-blind fashion, 90 ASA I-II patients (16-60 yrs) were studied, divided into three groups: Thirty patients received 1.0 mg.kg-1 diclofenac i.v. after general anaesthesia induction, before surgical incision, and four hours later the same dose was given i.m. Thirty patients received ketoprofen 1.35 mg.kg-1 i.v. and i.m., as above, and a third group of 30 patients received a comparable volume of saline i.v. and i.m. The patients received supplemental analgesia using a patient controlled analgesia apparatus; the rescue medication consisted of 0.03 mg.kg-1 oxycodone i.v. (four-hour maximum dose was 0.4 mg.kg-1) during the 24-hour follow-up. The three groups were comparable regarding the type of maxillofacial surgery (osteotomies vs. soft tissue surgery). Overall, there was a lower need for i.v. oxycodone during the 24-hour period in the diclofenac group (269 doses) than in the ketoprofen group and in the saline group (388 doses, each) (P < 0.01). The significantly lower number of oxycodone administrations in the diclofenac group was a result of a distinguishable difference, particularly during the first four hours after surgery. There was no statistically significant difference in the incidence of side effects of the analgesic therapy between the three groups.

The economic consequences of NSAID-induced gastropathy: the French context.

The costs of treating gastroduodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are shown to increase the total cost of NSAID treatment to the Assurance-Maladie, the French national health insurance system. This increased cost is termed the iatrogenic cost factor, and is defined as the ratio of the shadow price of an NSAID to its reimbursed cost. The shadow price is calculated from estimates of the incidence of NSAID-induced gastropathies, the cost of the drug, and the hospital and ambulatory costs of treating the gastropathies. The resulting iatrogenic cost factors are estimated as 1.36 for naproxen, 1.48 for sulindac, 1.65 for diclofenac, 1.67 for piroxicam, 2.00 for ketoprofen, and 2.12 for etodolac.

A comparative trial of ketoprofen and ibuprofen in patients with rheumatic disease.

A comparative controlled study was carried out in 40 patients suffering from rheumatoid arthritis, osteoarthrosis or ankylosing spondylitis to assess the efficacy of ketoprofen and ibuprofen. Patients were allocated at random to receive either 100 mg ketoprofen twice daily or 400 mg ibuprofen 3-times daily over a period of 3 months. Subjective overall assessments of symptoms, based on rating scale scores for pain, duration of morning stiffness and inflammation, showed that there was a greater, more rapid and more sustained improvement in those patients treated with ketoprofen. Measurements of inflamed joint size and of grip strength also improved more with ketoprofen than with ibuprofen. Side-effects, notably nausea, epigastric discomfort and abdominal pain, were more frequent and severe with ketoprofen, leading to the withdrawal of 2 patients in the early stage of the trial, and were probably related to the high dosage used. Three patients receiving ibuprofen needed 7 injections of ACTH to control their symptoms.