Although it is now known for about a hundred non-steroidal anti-inflammatory drugs (NSAIDs), different classes, looking for new members of this group continues. This is due to the need for drugs that have the optimal ratio of analgesic and anti-inflammatory effect and a high degree of safety. With traditional NSAIDs anti-inflammatory, antipyretic and Antianginal effects are always combined with ulcerogenic gastrotoksicheskim action and may cause damage to the lining of the gastrointestinal tract, renal dysfunction, etc. [1]. This risk is associated with the main mechanism of action of NSAIDs - non-selective inhibition of the biosynthesis of prostaglandins in various organs. These are widely used at present analgesic, metamizol as occurring in some combined drugs (baralgin, maksigan, etc.), as well as more modern ketorolac have an unfavorable side effect profile and low anti-inflammatory properties, while most other NSAIDs are insufficient analgesic properties [2,3]. Therefore, the appearance of the drug in the pharmaceutical market lornoksikam, produced by "Nycomed" brand "Ksefokam" [4], has attracted the attention of doctors of all specialties.
Ksefokam an NSAID with a pronounced analgesic effect by inhibiting prostaglandin synthesis, inhibition of isoenzymes of cyclooxygenase (COX) and suppress the formation of free radicals from activated leukocytes and leukotrienes. Ksefokam also stimulates endogenous dynorphin and endorphin, which is an additional physiological mechanism relieve pain syndromes of any intensity and localization [5].
The half-life of plasma Ksefokama approximately 4 h, significantly less than the same period of the other NSAID groups oxycam. Due to this short half-life of plasma Ksefokam has less severity of side effects, as in the period between doses may restore physiological levels of prostaglandins necessary to protect the stomach lining and maintain normal blood flow to the kidneys [6], with no accumulation and the risk of overdose [ 5].
The absolute bioavailability of 97%, the maximum concentration in plasma is reached after 15 min. after intramuscular injection, and the degree of plasma protein binding is 99%, which, however, does not prevent the penetration of its active in the joint. Research Ksefokama penetration into synovial fluid, including patients with associated rheumatoid arthritis or osteoarthritis in the knee joint exudation showed that the joints persists for a long time activity of the drug - even at a time when its concentration in plasma is reduced to a level preceding the introduction of dose [7]. The drug is completely metabolized in the liver under the action of cytochrome P450 to form a pharmacologically inactive metabolites, approximately one-third of whom excreted by the kidneys in the urine and two-thirds - the liver and intestine, while enteropechenochnaya circulation is absent. This dual path excretion reduces the load on these organs and improves the portability Ksefokama, so mild to moderate hepatic and / or renal failure, correction of the dose is not required [8]. Pharmacokinetic processes in the elderly and young people using the drug occur roughly equally, so a correct dose of the drug in the elderly is also not required [8].
Rapid Ksefokam: pills
at a rate of injecting drug
In order to achieve a rapid analgesic effect without the use of parenteral (intramuscular) route of administration, typical of the "standard" NSAID, has been developed by Nycomed product of new medical technologies - drug Ksefokam Rapid. This is a tableted product, which is designed for quick and effective treatment of acute pain.
Pharmacokinetics Ksefokama Rapid corresponds intramuscular route of administration of the drug. Start Time analgesic action of the drug is reduced from 30-40 to 10-15 min., Ie almost three-fold. This is achieved thanks to the unique composition and construction of a new pill Ksefokam Rapid. Lornoksikam contained in the tablet Ksefokam Rapid, placed in the microspheres coated with a buffer substance. Coating granules, reacting with gastric juice and creates slightly alkaline environment in which lornoksikam quickly dissolved and absorbed into the bloodstream.
In any drug must maintain a balance between efficacy and safety. In the case of gastrointestinal tolerability Ksefokamom good matches with greater than that of acetylsalicylic acid (ASA) and naproxen tramadol, analgesic effect, which gives him the position of a useful complement to a number of available NSAIDs. However, like other NSAIDs, may reduce Ksefokam glomerular filtration at a certain group of people, such as postoperative patients with reduced blood volume and electrolyte shifts, when the local synthesis of prostaglandins and their vasodilating effect is important to maintain renal homeostasis. Ksefokama action may cause further kidney damage, so patients in this category, he should be appointed with special precautions [9]. There were also changes in coagulation parameters (a slight increase in the time of hemostasis and coagulation time and a small reduction in thrombolytic activity), but these changes were within normal values [10]. In general, unlike other NSAIDs, has a low Ksefokam hepato-, nephro-and gematotoksichnosti, good gastrointestinal tolerability, its allergic potential was also found low [10].
Application Ksefokama
in neurological practice
Back pain is one of the most common reasons for seeking medical attention. NSAIDs are a major group of drugs for the treatment dorsalgia. The clinical trials have demonstrated efficacy in the treatment of Ksefokama both acute and chronic back pain.
Ksefokam 8 mg applied orally or intramuscularly, reduced pain better than placebo [11].
In another study showed that Ksefokam dose of 16 mg, administered orally, exerted analgesic effect in 94% of patients at 1 h after ingestion, and the average duration of response was 8-9 h [12].
Ksefokam 8 mg 2 times / day. has analgesic effect comparable to the effect of diclofenac 50 mg 3 times / day. and well tolerated [13].
After intravenous administration Ksefokama at 4 or 8 mg / day. patients with acute low back pain had clinical improvement. Scientists have also documented the increase in endogenous opioids, dynorphin and β endorphin. These data suggest that Ksefokam activates central mechanisms of analgesia [14].
A double-blind study involving 220 patients compared the Rapid Ksefokam with diclofenac potassium. The main purpose of the study was to determine the start time of the drug and its primary effect in the various courses of treatment. The results showed that the onset of pain relief occurred more quickly (about 6 min.) Ksefokama for Rapid, compared with diclofenac potassium, but this difference was not statistically significant (p = 0.51). Rapid Ksefokam reduced pain significantly better (p = 0.018 for total anesthesia, P = 0.003 for overall change in pain intensity) and was significantly more effective for the entire study period (6 days) [15].
Effectiveness has been demonstrated under more prolonged use Ksefokama. The results of 2 parallel, randomized, double-blind studies listed below.
Ksefokam 4 mg 2 times / day. and diclofenac 50 mg 2 times / day. during the 14-day study were more effective than placebo and had a comparable analgesic effect (80% of patients in each group experienced pain relief) [16].
Ksefokam 8 mg 2 times / day. on the effectiveness of pain management (both at rest and in motion) was superior to naproxen 500 mg 2 times / day. and placebo, and also had the best results in Oswestry questionnaire [Oswestry] (This questionnaire allows you to determine the degree of disability in low back pain). In addition, patients taking Ksefokam, used less additional analgesics than patients in other groups [17].
According to the study of interregional Pain Center in Novosibirsk in patients with vertebrogenic pain, the effect of Ksefokama 8 mg 2 times / day. within 3 weeks. efficacy and safety was much higher than the action of indomethacin 75 mg 3 times / day. [18].
Thus, an effective Ksefokam medicament for the treatment of back pain.
Application Ksefokama
in rheumatology
In addition to a strong analgesic effect, Ksefokam has expressed anti-inflammatory effect (in contrast to NSAIDs such as ketorolac, metamizol, paracetamol), which successfully allows its use in the treatment of rheumatic diseases.
The emergence of a new NSAID is particularly important because many patients do not meet the existing therapy drugs. Therefore, the appearance will become an extension Ksefokama used NSAIDs and optimize treatment of patients based on their individual merits. Particular attention is drawn messages that may stimulate Ksefokam synthesis of proteoglycans, as well as weaken the destructive effects that occur in rheumatoid arthritis [6,10,19].
Comparison with placebo and Ksefokama traditionally used to treat rheumatoid arthritis NSAIDs was carried out in more than 10 double-blind studies carried out both in Russia and abroad, and included a total of more than two thousand patients [7,10,20, 21]. Consideration was given index joints Ritchie, number of involved joints, duration of morning stiffness, pain relief and functional ability, and overall effectiveness evaluation made by patients and physicians. It has been shown that intake of even 2 mg Ksefokama 2 times / day. was more effective than placebo [22]. At the same time was marked by the relationship between dose and effect: receiving 4 mg Ksefokama 3 times / day. or 8 mg 2 times / day. was more effective than taking 2-4 mg 2 times / day. [10].
A comparison with piroxicam during the course of therapy at 12 weeks. showed that the use Ksefokama 4 mg 2 times / day. nearly the equivalent of receiving 20 mg of piroxicam [23]. When comparing Ksefokama and diclofenac for 12 weeks. greatest improvement in the index joints Richie was seen in patients taking Ksefokam 4 mg 3 times / day.
About the Author
Visit Independent Pharmaceutical Association certified by the American Naturopathic Medical Certification and Accreditation Board Inc. Commissioned by the American Association of Drugless Practitioners and a member of the American Academy of Anti-Aging, the American Academy of Pain Management and the Christian Medical & Dental Association.
