Analgesic Effects Of Ketoprofen Research Articles

Influence of obesity on pharmacokinetics and analgesic effect of ketoprofen administered intravenously to patients after laparoscopic cholecystectomy.

Ketoprofen is an analgesic drug commonly applied in the postoperative period, e.g., to patients after laparoscopic cholecystectomy. Many patients who undergo this procedure are obese. As pathophysiological changes are observed in obesity, the efficacy of ketoprofen may be altered in this group of patients. The aim of the study was to compare the pharmacokinetic parameters and analgesic effect of ketoprofen administered to obese and non-obese patients after laparoscopic cholecystectomy. The study was conducted on 41 patients after laparoscopic cholecystectomy, who were divided into two groups: obese (n = 21) and non-obese (n = 20). Ketoprofen was administered intravenously at a dose of 100mg. Plasma ketoprofen concentrations were measured by means of validated high-performance liquid chromatography with ultraviolet detection. The pharmacokinetic parameters of the drug were calculated using the non-compartmental method. Additionally, pain intensity was assessed during the study using NRS scale. The obese patients had significantly lower AUC0-∞ (1.4-fold), AUMC0-t (1.8-fold), AUMC0-∞ (3.2-fold), MRT0-t (1.4-fold), MRT0-∞ (2.3-fold), t0.5 (2.3-fold) and Vz/kg (2.3-fold) and higher kel (2.2-fold) than the non-obese group. Moreover, 4h and 6h after the administration of the drug, pain intensity was significantly higher in the obese patients. The drug was eliminated faster and the analgesic effect of ketoprofen in the obese patients was decreased as compared with the non-obese subjects. However, pain intensity did not increase to the level, which required additional analgesic treatment. Therefore, it seems that dosage adjustment of intravenous ketoprofen is not necessary in obese patients.

The Role of TRP and K+ Ion Channels in Analgesic Effect of NSAIDs

Objective: We aimed to clarify the possible contributions of TRP and voltagedependent K+ channels to the analgesic effects of diclofenac, ketoprofen, etodolac, and dipyrone using the nonselective TRP channel blocker ruthenium red and the voltage-dependent K+ channel blocker (Kv7; KCNQ) XE 991, respectively. Methods: We assessed the changes in the antinociceptive effects of diclofenac (50 mg/kg, i.p.), ketoprofen (50 mg/kg, i.p.), etodolac (70 mg/kg, i.p.), and dipyrone (500 mg/kg, i.p.) using ruthenium red (3 mg/kg, i.p.) and XE 991 (1 mg/kg, i.p.) before treatment in the hot plate, tail immersion, and writhing tests in mice. Results: In the tail immersion test, ruthenium red administration resulted in a significant reversal in the analgesic effects of dipyrone, etodolac, and ketoprofen. In the hot plate test, a significant reversal was observed in the analgesic effect of only dipyrone. In the tail immersion test, the administration of XE 991 induced a significant reversal in the analgesic effects of dipyrone and etodolac and a relative reversal in the analgesic effects of ketoprofen and diclofenac. In the hot plate test, XE 991 produced a significant reversal in the analgesic effect of only ketoprofen, whereas it caused a relative reversal in the analgesic effects of other tested nonsteroidal anti-inflammatory drugs (NSAIDs). In the writhing test, no significant change was observed after either XE 991 or ruthenium red administration. Concusions: Modulation of TRP and K+ channels may be involved in the central analgesic effects of NSAIDs. The clarification of different action mechanisms of NSAIDs will contribute to new therapeutic approaches and provide guidance for new drug development studies.

Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats

AimsThe aim of the present study was to investigate the effects and underlying mechanisms of endotoxin (lipopolysaccharide, LPS) on postoperative pain using a rat model of incisional pain. Main methodsAnimals were assigned to one of four groups using a 2×2 experimental design: a single intraperitoneal injection of 5mg/kg LPS versus vehicle, by plantar incision versus anesthesia alone. Spontaneous pain and mechanical paw withdrawal threshold (PWT) were evaluated using Rat Grimace Scale (RGS) and von Frey fibers, respectively. Analgesic effects of ketoprofen, morphine, and wound infiltration with ropivacaine, as well as the contribution of the Toll-like receptor (TLR) 4 pathway, were also evaluated. In vivo single fiber recordings were performed to assess the nociceptive afferent signals from the surgical site. Key findingsSystemic administration of LPS significantly increased the pain intensity at 2h after hind paw incision, but did not affect the PWT. The duration of post-incisional pain assessed by both scales did not significantly differ in the presence or absence of LPS. The analgesic efficiency of ketoprofen and morphine was reduced by LPS, while that of wound infiltration with ropivacaine was preserved. On the other hand, in vivo single fiber recording failed to demonstrate any significant effects of LPS on the activity of primary afferents due to mechanical stimuli. Pre-treatment with intrathecal LPS from Rhodobacter sphaeroides, a TLR-4 antagonist, almost completely inhibited LPS-induced exacerbated post-incisional pain, and decreased analgesic responsiveness. SignificanceThe present results suggested that LPS exacerbates post-incisional pain via the central TLR-4 pathway.

Ketoprofen in piglets: enantioselective pharmacokinetics, pharmacodynamics and PK/PD modelling

The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 μg/mL and an IC(50) for R-ketoprofen of 1.6 μg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.

Anti-inflammatory and Analgesic Effects of Ketoprofen in Palm Oil Esters Nanoemulsion

Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.

Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats

The purpose of this study was to evaluate percutaneous penetration and pharmacological effects of ketoprofen after transdermal administration, compared to the oral route. Skin and knee joint penetration of ketoprofen was tested by a microdialysis technique in rats and in vivo recovery was determined by retrodialysis. After oral and transdermal administration of ketoprofen, dialysate was sampled at 60 min intervals up to 360 min, for determination of concentrations of ketoprofen and prostaglandin E2. Analgesic effects of ketoprofen in iodoacetate and adjuvant-induced arthritis models were evaluated using the weight bearing method. The average recoveries of ketoprofen over 360 min in the skin and knee joint were 60.2 ± 3 and 15.8 ± 9%, respectively. Cmax values for ketoprofen absorbed within the skin after oral and transdermal administration were 20.1 ± 5 and 297.5 ± 478 ng/mL, respectively, and within the knee joint, 4.4 ± 0.4 and 2.7 ±0.9 ng/mL. The Cmax value for the plasma concentration of ketoprofen after oral administration was approximately 80 times higher than with the transdermal route. Both transdermal and oral administration of ketoprofen significantly decreased PGE2 production in the skin and knee joint and improved weight bearing after exposure to iodoacetate and adjuvant. These results indicate that the transdermal ketoprofen patch is a useful formulation that can deliver the drug in sufficient amounts to inhibit prostaglandin E2 production in the skin and knee joint.

Analgesic Effect of Ketoprofen Is Mainly Associated to its R-Enantiomer: Role of Cytokine Modulation

Analgesic Effect of Ketoprofen Is Mainly Associated to its <i>R</i>-Enantiomer: Role of Cytokine Modulation