Clinical use of ketoprofen lysine salt: a reappraisal in adolescents with acute respiratory infections.

Upper respiratory infections are widespread, and they are mainly of viral etiology. It has to be remarked that every infection is always associated with an inflammatory response. Inflammation implicates a cascade of bothersome symptoms, including fever, pain (headache, myalgia, and arthralgia), malaise, and respiratory complaints. As a result, anti-inflammatory medications could be beneficial as they act on different pathogenetic pathways. The ketoprofen lysine salt (KLS) has a potent anti-inflammatory activity associated with effective analgesic and antipyretic effects and has a valuable safety profile. However, adolescents present peculiar psychological characteristics that determine their difficulty to be managed. In this regard, an adolescent with a respiratory infection requires a prompt and adequate cure. KLS, thanks to its pharmacologic profile, could be favorably used in this regard. A recent primary-care experience outlined its effectiveness in this issue.

[Clinical parameters of the oral cavity in postmenopausal women during the course of a nonsteroidal anti-inflammatory drug]. / Klinicheskie parametry sostoyaniya polosti rta u zhenshchin postmenopauzal'nogo perioda pri kursovom primenenii nesteroidnogo protivovospalitel'nogo preparata.

THE AIM OF THE STUDY: Was to assess the clinical effectiveness of the course of ketoprofen lysine salt after its oral application in postmenopausal women with vitamin D deficiency in the complex therapy of inflammatory periodontal diseases. MATERIALS AND METHODS: The study comprised 100 women with decreased bone mineral density and chronic generalized mild to moderate periodontitis. The average age was 55.3±1.9 years with menopause lasting for more than 5 years (6.0±0.8) and the average age for the onset of menopause of 48.9±1.5 years. The study participants were divided into four groups (two main groups and two comparison groups). The patients underwent periodontal treatments and received native vitamin D prescriptions in accordance with clinical guidelines and treatment protocols. RESULTS: Serum vitamin D for the patents of the first and second groups was 11.4±1.9. Vitamin D level in the comparison groups was 34.6±3.2. The study reveals the direct correlation of chronic periodontitis, the level of bone mineral density and vitamin D deficiency in older female patients. The effects are proved by reduction of indices like PMA, Mulleman bleeding index and periodontal index for all study groups. Correlation of anti-inflammatory activity of the solution with the reduction in pockets depths was 0.46 mm along with improvements in syalometry. Organoleptic properties of the tested oral solution of ketoprofen lysine salt were positively evaluated by all participants, subjective assessments of «color¼, «treatment effect¼ and «prolonged analgesic effect¼ received the highest scores. CONCLUSION: Ketoprofen lysine salt solution has shown significant anti-inflammatory, antioedemic and hemostatic activity of the drug in therapy of chronic generalized mild to moderate periodontitis in older female patients.

[What factors affect the effectiveness of long - term analgesic therapy for osteoarthritis? Data analysis of the multi - center 3-month PARACELSUS study].

There are factors that can affect the effectiveness of treatment of osteoarthritis (OA). Aim to identify factors affecting the effectiveness of long - term analgesic therapy in OA. Materials and methods. The study included 6448 patients (70.9% female and 29.1% male), middle age 57.8±10.2 years, with severe pain [≥40 mm on the visual analog scale]. All patients received the preparation of avocado - soybean unsaponifiables (ASU) 300 mg/day. For pain relief at the beginning and during the study, the drug Ketoprofen lysine salt (KLS) 320 mg/day was used. The efficiency criterion was pain reduction ≥50% and satisfaction with treatment ≥4 on a 5-point scale. The influence of a number of factors on the result of treatment was evaluated. Results. For 3 months of treatment, the pain decreased from 63.7±12.0 to 14.2±11.7 mm VAS. The result was evaluated as "good" or "excellent" 81.7% of patients. Adverse reactions were rare. In total, a good response to therapy was noted in 87.4% of patients. Gender, body mass index ≥30 kg/m2, type 2 diabetes mellitus, poor effect of non - steroidal anti - inflammatory drugs (NSAIDs) and Symptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOA) in history did not affect the result. The effect was lower in persons >65 years [odds ratio (OR) 0.418; 95% confidence interval (CI) 0.342-0.509, p2 by Kellgren-Lawrence (OR 0.556; 95% CI 0.298-0.738, p.

[The application of different non-steroidal anti-inflammatory drugs for the elimination of pain syndrome during the early postoperative period in the children following the surgical interventions on palatine tonsils]. / Ispol'zovanie nesteroidnykh protivovospalitel'nykh sredstv dlia kupirovaniia bolevogo sindroma posle tonzillotomii u detei.

The present clinical study included 120 children at the age varying from 6 to 18 tears who had undergone radiowave tonsillotomy followed by symptomatic therapy during the early postoperative period with the application of different non-steroidal anti-inflammatory drugs. All the patients were randomly allocated to four groups each comprised of the equal number of patients. Those of group 1 were treated with ketoprofen lysine salt (КLS) in the form of a solution for oral intake in case of complaints of severe pain in the throat. The patients of group 2 received courses of ketoprofen lysine salt therapy per os thrice daily during 3 days after the surgical intervention. The patients of group 3 were given ibuprofen per os up to three times every day in case of complaints of severe pain in the throat. The patients of group 4 were treated with ketoprofen lysine salt in the form of a solution for the local application twice daily during 3 days after the surgical intervention. The results of the analysis with the use of the analog-visual scale have demonstrated that a decrease in pain intensity within 24 hours after surgery was much more pronounced in the patients of group 2 in comparison with those of the remaining three groups (р<0.05). The difference of pain intensity in the throat evaluated based on the analog-visual scale between the patients of groups 1, 3, and 4 was insignificant (p>0.05). None of the children exhibited the signs of bleeding throughout the entire observation period. It can be concluded that a course of therapy with the use of ketoprofen lysine salt for oral intake during the early period after the surgical intervention for radiowave palatine tonsillotomy has some advantages over a single intake of the analogous preparation (for alleviation of strong pain in the throat), an ibuprofen syrup or a ketoprofen lysine salt solution for throat wash.

Natural polysaccharides platforms for oral controlled release of ketoprofen lysine salt.

CONTEXT: Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1-2 h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity. OBJECTIVE: In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release. MATERIALS AND METHODS: Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment. RESULTS AND DISCUSSION: Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DR®caps) a delivery platform has been developed to control KL release in a delayed (90 min lag time) and prolonged way (270 min complete release). CONCLUSION: The platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.

Comparison of the effects of ketoprofen and ketoprofen lysine salt on the Wistar rats' nervous system, kidneys and liver after ethyl alcohol intoxication.

Side effects of Ketoprofen and ketoprofen lysine salt (KLS) may be inter alia from the central nervous system, kidneys and liver. After binge drinking people often use ketoprofen, which increases the risk for the occurrence of side effects. The aim of the study was to compere effects of ketoprofen and KLS on the nervous system, kidneys and liver after ethyl alcohol intoxication. There were 6 groups of 6 male rats which received: ethanol; 0.9%NaCl; 0.9%NaCl and ketoprofen; ethanol and ketoprofen; 0.9%NaCl and KLS; ethanol and KLS. On day 2, the motor coordination test on a rotary rod and memory and motor activity test in the Y-maze were performed. Hot plate test was performed on day 6. After euthanasia brains, livers and kidneys were taken to histopathological tests. Motor coordination was significant worse in group 5 vs 1,3, p 0.05. Spontaneous motor activity of group 6 was significant better than that of groups 1,5. Pain tolerance of group 6 was significant worse than that of groups 1,4,5. Liver and kidney mass were significantly lower in group 6 vs group 3,5 and vs group 1,3, respectively. The histopathologic examination of the brains and kidneys revealed normal picture in all groups, without signs of inflammation. In the histopathologic examination of the livers in one animal in group 3 some of the specimens showed perivascular inflammation. After alcohol ketoprofen is a better painkiller than KLS. Spontaneous motor activity is better after KLS after alcohol. Both drugs have a similar effect on the kidneys and liver.

Ketoprofen, lysine and gabapentin co-crystal magnifies synergistic efficacy and tolerability of the constituent drugs: Pre-clinical evidences towards an innovative therapeutic approach for neuroinflammatory pain.

Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage. To leverage these supra-additive effects, we then chemically combined the two drugs via co-crystallization to yield a new compound, a ternary drug-drug co-crystal of ketoprofen, lysine and gabapentin (KLS-GABA co-crystal). Physicochemical, biodistribution and pharmacokinetic studies showed that within the co-crystal, ketoprofen reaches an increased gastrointestinal solubility and permeability, as well as a higher systemic exposure in vivo compared to KLS alone or in combination with gabapentin, while both the constituent drugs have increased central nervous system permeation. These unique characteristics led to striking, synergistic anti-nociceptive and anti-inflammatory effects of KLS-GABA co-crystal, as well as significantly reduced spinal neuroinflammation, in translational inflammatory and neuropathic pain rat models, suggesting that the synergistic therapeutic effects of the constituent drugs are further boosted by the co-crystallization. Notably, while strengthening the therapeutic effects of ketoprofen, KLS-GABA co-crystal showed remarkable gastrointestinal tolerability in both inflammatory and chronic neuropathic pain rat models. In conclusion, these results allow us to propose KLS-GABA co-crystal as a new drug candidate with high potential clinical benefit-to-risk ratio for chronic pain treatment.

Ketoprofen lysine salt has a better gastrointestinal and renal tolerability than ketoprofen acid: A comparative tolerability study in the Beagle dog.

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.

The effect of ketoprofen lysine salt on mucosa of rat stomach after ethyl alcohol intoxication.

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.