Doses Of Flurbiprofen Research Articles

Diz Osteoartritli Hastalarda Tek Doz Transdermal Flurbiprofen Uygulamasının Etkinliği

Objective: Nonsteroidal anti-inflammatory drugs (NSAID) are among the most widely prescribed agents in osteoarthritis patients, and may lead to important side-effects which increase the risk of hospitalization and death. Transdermal administration of NSAIDs can provide relief of pain locally with relatively less side effects. This study was aimed to evaluate the efficacy of a single administration of 40 mg transdermal flurbiprofen on pain and on strength of quadriceps and hamstring muscles in patients with knee osteoarthritis. Material and Methods: This study is a double blind, placebo-controlled cross-over preliminary study. Transdermal flurbiprofen and placebo patches were administered to the 24 patients with knee osteoarthritis. Knee pain was evaluated using a visual analog scale (VAS) and the strength of quadriceps and hamstring muscles using an isokinetic dynamometer. Results: Mean VAS scores reduced from 5.3 ± 1.7 to 4.7 ± 1.6 (p= 0.88) after placebo administration, and from 5.4 ± 1.9 to 3.9 ± 1.7 (p= 0.04) following flurbiprofen administration. Peak torque and total work values of flexor and extensor muscles of knee did not differ statistically after flurbiprofen or placebo administrations. Conclusion: Pain significantly reduced after single dose of transdermal flurbiprofen patch. However, no significant difference in isokinetic assessment parameters was observed in the present study. To assess the effects of transdermal flurbiprofen and its efficacy on knee pain and function, further controlled studies in larger groups of patients with different doses of flurbiprofen are recommended.

Immediate hypersensitivity reaction to a single oral dose of flurbiprofen

Immediate hypersensitivity reaction to a single oral dose of flurbiprofen

Single dose oral flurbiprofen for acute postoperative pain in adults.

Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions.The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25% and 16% of participants with flurbiprofen 50 mg and 100 mg over 6 hours, compared with almost 70% with placebo.Adverse events were uncommon, and not significantly different from placebo. Flurbiprofen at doses of 50 mg and 100 mg is an effective analgesic in moderate to severe acute postoperative pain. The NNT for at least 50% pain relief is similar to that of commonly used NSAIDs such as ibuprofen and naproxen at usual doses. Use of rescue medication indicates a duration of action exceeding 6 hours.

Differential Genotype Dependent Inhibition of CYP2C9 in Humans

The effects of genetic polymorphisms in drug-metabolizing enzymes (e.g., CYP2C9(*)3) on drug clearance have been well characterized but much less is known about whether these polymorphisms alter susceptibility to drug-drug interactions. Previous in vitro work has demonstrated that genotype-dependent inhibition of CYP2C9 mediated flurbiprofen metabolism, suggesting the possibility of genotype-dependent inhibition interactions in vivo. In the current study, flurbiprofen was used as a probe substrate and fluconazole as a prototypical inhibitor to investigate whether genotype-dependent inhibition of CYP2C9 occurs in vivo. From 189 healthy volunteers who were genotyped for CYP2C9 polymorphisms, 11 control subjects (CYP2C9(*)1/(*)1), 9 heterozygous and 2 homozygous for the CYP2C9(*)3 allele participated in the pharmacokinetic drug interaction study. Subjects received a single 50-mg oral dose of flurbiprofen alone or after administration of either 200 or 400 mg of fluconazole for 7 days using an open, randomized, crossover design. Flurbiprofen and fluconazole plasma concentrations along with flurbiprofen and 4'-hydroxyflurbiprofen urinary excretion were monitored. Flurbiprofen apparent oral clearance differed significantly among the three genotype groups (p < 0.05) at baseline but not after pretreatment with 400 mg of fluconazole for 7 days. Changes in flurbiprofen apparent oral clearance after fluconazole coadministration were gene dose-dependent, with virtually no change occurring in (*)3/(*)3 subjects. Analysis of fractional clearances suggested that the fraction metabolized by CYP2C9, as influenced by genotype, determined the degree of drug interaction observed. In summary, the presence of CYP2C9(*)3 alleles (either one or two alleles) can alter the degree of drug interaction observed upon coadministration of inhibitors.

Ginkgo biloba Does Not Alter Clearance of Flurbiprofen, a Cytochrome P450‐2C9 Substrate

The effect of Ginkgo biloba on the activity of CYP2C9, the isoform responsible for S-warfarin clearance, was assessed in 11 healthy volunteers who received single 100-mg doses of flurbiprofen, a probe substrate for CYP2C9. Subjects also received either a standardized G biloba leaf preparation (Ginkgold, 3 doses of 120 mg) or matching placebo in a randomized, double-blind, 2-way crossover study. Mean kinetic variables for flurbiprofen with either placebo or G biloba were elimination half-life, 3.9 versus 3.5 hours; total AUC, 57 versus 55 microg/mL h; and oral clearance, 32.9 versus 31.6 mL/min. None of these differences was significant. Based on highperformance liquid chromatography analysis, each 60-mg Ginkgold tablet contained 6.6 mug of amentoflavone and 61.2 microg of quercetin, both previously identified as CYP2C9 inhibitors. These amounts were apparently too low to inhibit CYP2C9 function in vivo. The results confirm previous controlled clinical studies showing no effect of ginkgo on the kinetics or dynamics of warfarin.

Beneficial effects of NO-releasing derivative of flurbiprofen (HCT-1026) in rat model of vascular injury and restenosis.

One of the major problems related to the percutaneous transluminal coronary angioplasty technique is the renarrowing of the vessel, a phenomenon known as restenosis. NO and nonsteroidal anti-inflammatory drugs have been shown to play a role in this pathology. The main problem with the use of conventional NO donors is that they affect blood pressure and flow, and for these reasons, they cannot be used safely in clinical practice. The aim of this study was to evaluate, with the use of a rat model of balloon angioplasty, whether a structural derivative of flurbiprofen, containing an added NO-releasing moiety (HCT-1026), is able to reduce or prevent neointimal formation. Rats were treated for 14 days with equimolar doses of flurbiprofen (2, 7, and 21 mg/kg) or HCT-1026 (3, 10, and 30 mg/kg). After this 14-day treatment, HCT-1026 but not flurbiprofen significantly modified the neointima/media ratio. The reduction in the neointimal proliferation obtained with HCT-1026 was well correlated with an increase in nitrite/nitrate plasma levels and a reduced cell proliferation. Neither HCT-1026 nor flurbiprofen affected inducible NO synthase induction in injured vessels. In conclusion, HCT-1026 caused a significant reduction in restenosis that appears to be directly related to NO release. HCT-1026 may prove to be beneficial in preventing or delaying restenosis in humans.

Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs.

The effect of several nitric oxide releasing-non-steroidal anti-inflammatory drugs (NO-NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC(50), 688.8+/-93.8 microM), nitroaspirin (NOA; EC(50), 57.9+/-6.5 microM), nitroparacetamol (NOPARA; EC(50), 71.5+/-14.6 microM) and nitroprednisolone (EC(50), 15.1+/-1.4 microM) caused concentration-related relaxation of noradrenaline (NA)-contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC(50), 35.7+/-3.5 nM). The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 microM) and reduced by ODQ (5 microM). Flurbiprofen and paracetamol (100 microM) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L-NAME (100 microM; EC(30), 181.8+/-35.1 microM cf. EC(30), 125.1+/-17.0 microM, P>0.05) but increased by removal of the endothelium (EC(30), 164.3+/-26.3 microM cf. EC(50), 688.8+/-93.8 microM, P<0.05). NOF (0.1 - 50 microM) produced a small but not concentration-related vasodilation of the NA-preconstricted (i.e. "high tone") perfused rat mesentery preparation (cf. SNP, EC(30), 4.4+/-0.7 microM). In contrast, NOF (1 - 100 microM) produced concentration-related vasodilation of the "high tone" perfused rat kidney with an EC(50) of 33.1+/-4.4 microM. Neither NOF (74 mg kg(-1), i.p.) nor NOA (91.9 mg kg(-1), i.p.) nor equimolar doses of flurbiprofen (50 mg kg(-1), i.p.) or aspirin (50 mg kg(-1), i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone-anaesthetized rats over a 1 h period. NO-NSAID relax blood vessels in vitro by an NO-dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations.

The effect of a prophylactic dose of flurbiprofen on muscle soreness and sprinting performance in trained subjects

The aim of this study was to examine the effects of a prophylactic dose of a local, transcutaneously administered, non-steroidal anti-inflammatory drug on muscle soreness, muscle damage and sprinting performance in young trained males. Twenty-five subjects aged 19 3 years, actively participating in rugby union and field hockey, were familiarized with the test procedure and then divided at random into an experimental group (n=13) and a control group (n=12). The experimental group received two patches, each containing 40 mg flurbiprofen (TransAct LATTM), 12 h before an exercise bout designed to produce delayed-onset soreness (DOMS). The control group received identical non-medicated placebo patches at the same time. Delayed-onset muscle soreness was induced by an exercise protocol consisting of drop jumps (seven sets of 10 repetitions). Serum creatine kinase activity, muscle soreness, muscle girth and acceleration in a maximal sprint over 30 m were measured before the induction of DOMS and at 12, 24, 48 and 72 h thereafter. Plasma lactate concentration was measured 3 min after the 30-m sprint tests. Subjects in both groups had significantly more pain at 24 and 48 h compared with at 12 and 72 h ( P < 0.05; Friedman two-way analysis of variance). Thigh girth and serum creatine kinase did not change throughout the experiment. Although plasma lactate concentrations were elevated after the 30-m sprint, there were no differences between groups or as a result of DOMS. The greatest acceleration occurred between 5 and 10 m. This was not affected by the anti-inflammatory drug or DOMS. In conclusion, the aetiology of the DOMS induced in the trained subjects in this study seems to be independent of inflammatory processes or, more specifically, of increases in prostaglandin synthesis in the muscles.

The efficacy of ANSAID (flurbiprofen) as an analgesic in foot surgery

Eighty-three patients scheduled for outpatient surgery were enrolled in this double-blind, randomized trial designed to compare the safety and efficacy of single and multiple doses of flurbiprofen 50 mg. and acetaminophen 300 mg. plus codeine phosphate 30 mg. During the multiple dose segment, statistically significant differences were observed during the first 24 hour postoperative period regarding relief of pain and pain intensity. Flurbiprofen provided greater relief of pain than the acetaminophen with codeine phosphate combination. This study supports the use of flurbiprofen as a suitable alternative to acetaminophen plus codeine phosphate in the treatment of postoperative pain following foot surgery.

Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal

The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg, acetaminophen 650 mg plus codeine 60 mg, and placebo. Subjects undergoing the surgical removal of impacted third molars were randomly administered one of the five treatments after the onset of moderate to severe postoperative pain. Pain intensity, pain relief, and side effects were evaluated for 6 hours after drug administration. Both doses of flurbiprofen resulted in significant analgesia in comparison with placebo, acetaminophen, and acetaminophen plus codeine as measured by pain intensity difference, pain relief, and global evaluation. The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine, and the fewest side effects were reported by subjects administered flurbiprofen. The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain, in ambulatory patients.

Synergistic anti-nociceptive effect of L-NG-nitro arginine methyl ester (L-NAME) and flurbiprofen in the mouse.

1. L-NG-nitro arginine methyl ester (L-NAME) administered i.p. produces anti-nociception in the mouse assessed by the formalin-induced paw licking and acetic acid-induced abdominal constriction models. The non-steroidal anti-inflammatory drug (NSAID), flurbiprofen, was similarly anti-nociceptive in both models. 2. Combination of a sub-threshold dose of L-NAME (10 mg kg-1) with increasing doses of flurbiprofen (25- 75 mg kg-1) or a sub-threshold dose of flurbiprofen (50 mg kg-1) with increasing doses of L-NAME (10- 100 mg kg-1) resulted in potentiated anti-nociception in the formalin model. Combined therapy with sub-threshold doses of L-NAME (10 mg kg-1) and indomethacin (10 mg kg-1) also resulted in significant anti-nociception. In addition, combining sub-threshold doses of L-NAME (12.5 mg kg-1) and flurbiprofen (2 mg kg-1) significantly reduced acetic acid-induced abdominal constriction. 3. L-NAME (10 mg kg-1) administered i.p. caused a significant (approximately 35%) increase in MAP in the urethane-anaesthetized mouse. Flurbiprofen (50 mg kg-1) was inactive. Combination treatment with L-NAME (10 mg kg-1) and flurbiprofen (50 mg kg-1) failed to elevate MAP above that observed with L-NAME alone. Neither L-NAME (10 mg kg-1) nor flurbiprofen (50 mg kg-1) either alone or in combination significantly altered mouse locomotor activity. 4. These results suggest that L-NAME and flurbiprofen/indomethacin act synergistically in their anti-nociceptive action in the mouse. Combination therapy with L-NAME and flurbiprofen and a similar NSAID may provide an alternative to the clinical control of pain in man.

潰ようの軽減を目的とした抗炎症薬フルルビプロフェンキメラドラッグの合成とｉｎ ｖｉｖｏ評価

The antiinflammatory effect, gastrotoxicity and in vivo absorption property of chimera drug of flurbiprofen(FP)with histamine H2-antagonist, PPA, were compared with those of FP and FP methyl ester. FP-PPA chimera drug and FP methyl ester were little hydrolyzed in the buffer of the pH 1.2 to 7.4 region in the absence or presence of pepsin and trypsin, in contrast to fast hydrolysis(t1/2 : about 20 sec)in rat plasma. FP chimera drug inhibited carrageenin induced paw swelling in the same level as FP alone. FP-PPA chimera drug significantly reduced gastrotoxicity in comparison to equivalent dose of FP, whereas the coad-ministration of FP with PPA did not affect gastrotoxicity of FP. FP methyl ester caused slightly less damage to the gastric mucosa than FP alone. The plasma concentration of FP after administration of FP derivatives were similar to FP alone. These data suggested that chimera drug is effective for reduction of gastric damage, compared with either FP or alkyl ester prodrug like methyl ester.

Influence of fever and flurbiprofen on trypanosome growth

The administration of flurbiprofen, a potent non-steroidal anti-inflammatory drug (NSAID), to goats infected with trypanosomes resulted in high elevated parasitaemia and suppression of fever. In contrast to goats, rats infected with trypanosomes do not show febrile reactions. Therefore, the role of body temperature was investigated with yeast-induced fever in Trypanosoma evansi and T. brucei infected rats. These investigations did not support the hypothesis that a high body temperature causes a drop in parasitaemia. In goats infected with trypanosomes, it is also unlikely that fever has an inhibitory influence on the parasitaemia. In these animals, rises in parasitaemia could be provoked by doses of flurbiprofen as low as 1 20 of the normal doses and these doses did not or only partly suppressed fever. No effect on parasite growth could be obtained when flurbiprofen was added in concentrations up to 32 μg/ml directly to T. brucei cultures. Moreover, no growth promoting factor(s) could be identified in vitro in serum from flurbiprofen-treated goats.

Flurbiprofen in post-partum women: plasma and breast milk disposition.

The plasma and milk disposition of flurbiprofen (FB) was assessed in healthy women during the early post-partum period after multiple doses of FB. The results confirmed that a pragmatic study design is an attainable requirement for definitive statements about the excretion of FB in transitional milk. Nine doses of FB (50 mg per dose) were administered during three days. Paired milk and plasma samples were obtained during this period of dosing as well as after the last dose. The plasma data were used to derive an equation, which was then used to simulate cumulative plasma profiles for multiple doses given at unequal time intervals. The observed data corresponded to the simulated cumulative profiles of FB in plasma. The plasma elimination half-life of FB during early lactation was slightly prolonged (mean 4.8 hrs) as compared to reported values for normal adult men. The peak plasma concentrations of FB were comparable to those reported for healthy volunteers. In 10 of 12 women (3-5 days post-partum) the FB concentration in breast milk was less than 0.050 micrograms/ml. In two women the milk concentrations of FB were 0.06, 0.07 and 0.07 micrograms/ml as found in only three samples. We conclude that, on the basis of dose found in milk, FB is safe for women breast feeding their infants in the early post-partum period.

Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain

The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 50 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p ≤0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac.

Effects of flurbiprofen and aspirin on the gastric and duodenal mucosa: An endoscopic comparison

A single-blind, randomized endoscopic tolerance study was conducted to compare daily doses of flurbiprofen (Ansaid, Upjohn) at 100, 150, and 200 mg per day with 2,600 mg of aspirin per day. Ten normal volunteers were enrolled in each of the flurbiprofen groups, and five were enrolled in the aspirin group. Analysis of the mean gastric mucosal injury scores obtained on day eight revealed statistically significant lower mean scores (p = 0,05) in the 100-mg and 150-mg flurbiprofen treatment groups when compared with the 200mg flurbiprofen group and the aspirin group. No significant differences were found between any of the treatment groups in duodenal mucosal injury scores. Mean scores for gastric mucosal Injury in the three groups receiving flurbiprofen showed a definite dose relationship. The aspirin-treated subjects had significantly decreased uric acid levels (p = 0.006) and a significantly higher incidence of tinnitus (p = 0.04) compared with the flurbiprofen treatment groups. There was a poor correlation between subjective symptomatology and endoscopic pathologic findings.

Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis.

Clinical assessment, plasma and synovial fluid kinetics were studied in 29 rheumatoid patients receiving 100 mg flurbiprofen twice daily. Clinical assessment and pharmacokinetic measurements varied widely within the group of patients. The average values for plasma clearance, volume of distribution and elimination halflife of flurbiprofen were 0.65 +/- 0.24 ml min-1 kg-1, 0.160 +/- 0.093 l kg-1 and 3.1 +/- 1.7 h, respectively. Synovial fluid drug concentrations peaked later and were lower than corresponding plasma concentrations: 5.2 h and 4.4 mg l-1 as against 1.49 h and 12.5 mg l-1, respectively. At 48 h after an oral dose of flurbiprofen, all the drug had been cleared from the synovial fluid. Synovial fluid drug concentrations were not related to synovial fluid albumin concentration or pH. There was a weak relationship between synovial fluid drug concentration and the thermographic measurements of disease activity. The fractions of flurbiprofen not bound to protein in synovial fluid and plasma were not significantly different. A simple model is proposed to account for the plasma and synovial fluid pharmacokinetics.

Effect of flurbiprofen, a cyclooxygenase inhibiting drug, on induced allergic rhinitis

To test whether prostaglandins contribute to the nasal allergic reaction, we subjected allergic rhinitis patients to nasal allergen challenge after treatment with flurbiprofen, a cyclooxygenase inhibitor. We challenged 18 patients after two pretreatment doses of flurbiprofen, 75 mg, chlorpheniramine, 6 mg, both drugs combined, and placebo. All patients received all treatments. None of the treatments affected measured nasal airway resistance. Nasal secretion weight, number of sneezes, and overall subjective severity scores for all active treatments differed significantly from placebo treatment. Flurbiprofen proved nearly as effective as chlorpheniramine in reducing severity of induced rhinitis. Some mechanism that can be influenced by flurbiprofen (possibly prostaglandin synthesis) contributes to the acute, induced allergic reaction.

Pharmacokinetics of oral and rectal flurbiprofen in children.

Eight subjects, aged 6-12 years and weighing 18.8-36.7 kg, received single doses of flurbiprofen 50 or 75 mg (corresponding to 1.4-2.7 mg/kg) as syrup and suppository in a Latin square design. Half-life (2.7-3.2 h), elimination constant (0.22-0.26 h-1), area under the plasma level curve (72.4-77.3 micrograms X h X ml-1) and time to reach the concentration peak (1-0.75 h) were similar after the syrup and suppository. Flurbiprofen showed equivalent bioavailability after oral and rectal administration and the same pharmacokinetic profile was confirmed in children as observed in adults.

Effect of flurbiprofen on bleeding time and platelet aggregation

Bleeding times were performed in normal subjects 4 hours after a single oral dose of flurbiprofen. There was a significant prolongation of the mean bleeding time after a 25 mg, but not after a 10 mg dose. The mean bleeding time was prolonged in 42 patients with acute myocardial infarction who received 25 mg flurbiprofen 8th hourly for 5–6 days and the effect persisted for the duration of therapy. In about 10% of patients, the bleeding time was prolonged beyond the upper limit of the normal range. Regular administration of flurbiprofen caused a persistent inhibition of the biphasic response and a reduction in the degree of platelet aggregation with adrenaline; it also prolonged the lag phase and reduced both the slope and degree of aggregation with collagen.