ketoprofen-lysine and Inflammation

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.

Topics: Alcoholic Intoxication; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ethanol; Inflammation; Ketoprofen; Kidney; Liver; Male; Nervous System; Rats; Rats, Wistar; Sodium Chloride; Sodium Chloride, Dietary

The purpose of this study was to assess the efficacy of topically applied ketoprofen lysine salt (KLS), a cyclooxygenase inhibitor, against the inflammatory changes induced by interleukin-1beta (IL-1beta) and bradykinin (BK) in hamster cheek pouch microcirculation. In addition, we characterised the pharmacological regulation of IL-1beta activity in this model.. Male Syrian hamsters were used. Microcirculation was visualised by fluorescent microscopy. Leukocyte adhesion, permeability, perfused capillary length (PCL) and capillary red blood cell (RBC) velocity were evaluated.. KLS (25 microg/ml/min to 1.6 mg/ml/min) was topically applied for 3 min before topically administered IL-1beta (1microg/ml) and BK (10(-4) M). Monoclonal anti-mouse IL-1beta receptor antagonist (200 ng/ml), BK-B2 receptor antagonist (10(-6) M), PAF inhibitor (10(-5) M) and cycloheximide (10 microg/ml) were added topically 15, 10, 15 and 60 min, respectively, before IL-1beta (1 microg/ml).. IL-1beta caused a significant increase in microvascular permeability, a decrease in capillary RBC velocity followed by increased leukocyte adhesion in postcapillary venules. BK caused a marked increase in leukocyte adhesion and no decrease in PCL and RBC velocity. Treatment with KLS significantly inhibited both the leukocyte adhesion and microvascular leakage induced by the two mediators. The inflammatory effects induced by IL-1beta were reduced by blockade of IL-1beta receptors and by a BK-B2 receptor antagonist but were not affected by a PAF antagonist and protein synthesis inhibition.. These results demonstrate that KLS is effective in preventing early inflammatory changes induced by both IL-1beta and BK in the capillary network. Prostaglandin release and BK are essential components for IL-beta mediated responses, whereas neither PAF nor new protein synthesis appear to be linked to the early inflammatory changes induced by IL-1beta.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Bradykinin Receptor Antagonists; Capillary Permeability; Cricetinae; Humans; Inflammation; Interleukin-1; Ketoprofen; Lysine; Male; Mesocricetus; Microcirculation; Mouth Mucosa; Platelet Membrane Glycoproteins; Protein Synthesis Inhibitors; Receptor, Bradykinin B2; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Interleukin-1

The aim of this study was to evaluate the percutaneous permeation of a new topical Gel-Spray formulation, containing 15% of ketoprofen lysine salt (KLS), both in vitro, using the Franz-type diffusion cells and in vivo, by evaluating urinary recovery after topical administration and to correlate the absorption data with KLS pharmacological activity in the rat. Concentrations of ketoprofen free acid (KFA) were determined by HPLC in the receptor compartment (in vitro), or in urine (in vivo). The permeation of ketoprofen evaluated in vitro after the application of KLS Gel-Spray was higher than that observed with the marketed formulation Profénid gel (containing KFA at 2.5%). The same evidence was found in vivo, except when the ratio between the administered dose and the area treated was higher than 1 mg cm-2. Thus, the difference between the two formulations seems to be the resultant of two opposing components: a positive gradient of concentration that favours the absorption of ketoprofen from KLS Gel-Spray and the presence of the enhancer ethanol that could favour the efficacy of Profénid gel. Under our conditions the former prevailed. As for the efficacy, evaluated in the carrageenan-induced oedema and hyperalgesia model, KLS Gel-Spray confirmed the data obtained for in vivo absorption, being more efficient than the reference standard Profénid gel. The observed inhibitory effects were due only to dermal absorption, oral absorption was excluded by an Elizabethan collar applied around the neck of the rat. In these experimental conditions, no significant damage of the rat stomach mucosa was observed. These results indicate that KLS Gel-Spray, due to its high KLS concentration, allows a very high efficiency in delivering ketoprofen to the inflamed area using a minimal amount of formulation, even in the absence of permeation enhancers.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Gels; In Vitro Techniques; Inflammation; Ketoprofen; Lysine; Pain Threshold; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Stomach

The anti-inflammatory and analgesic profile of a new topical foam formulation of ketoprofen lysine salt (CAS 57469-78-0, Artrosilene Schiuma, KLS-foam) was characterized in comparison with marketed gel formulations containing KLS (KLS-gel) or diclofenac diethylammonium salt (DCF-gel). KLS-foam dose-dependently inhibited oedema formation and hyperalgesia induced by subplantar injection of carrageenan or substance P, being more potent than KLS-gel. At equieffective anti-inflammatory doses, KLS-foam provided a more pronounced analgesic effect than DCF-gel. KLS-foam also markedly inhibited exudate formation and prostaglandin production induced by subcutaneous implantation of carrageenan soaked sponges. In carrageenan induced paw inflammation, KLS-foam provided the same anti-inflammatory effect as orally administered KLS, but induced significantly less gastric damages. Oral administration of KLS resulted in sustained systemic absorption of ketoprofen, whereas after topical application of KLS-foam no appreciable ketoprofen plasma levels were detected. These data support the anti-inflammatory and particularly the analgesic effectiveness of the new foam formulation of KLS, a finding that, together with the high gastric tolerability, further emphasizes the usefulness of KLS-foam in the treatment of localized flogistic diseases and associated pain.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Diclofenac; Exudates and Transudates; Female; Gastric Mucosa; Gels; Hyperalgesia; Inflammation; Ketoprofen; Lysine; Male; Prostaglandins; Rats; Rats, Sprague-Dawley; Substance P