Ibuprofen Arginine Research Articles

Antimicrobial Activity and Cytotoxicity of Nonsteroidal Anti-Inflammatory Drugs against Endodontic Biofilms.

Persistent infections have become a challenge in dentistry because of growing antibiotic resistance. Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be a therapeutic alternative to control biofilm infection. The objective of this work is to evaluate the antimicrobial activity and cytotoxicity of sodium diclofenac (DCS), ibuprofen (IBP) and ibuprofen arginine (IBP-arginine) solutions against endodontic polymicrobial biofilms. Sterile radicular dentin blocks of 4 mm × 4 mm × 0.7 mm were used as substrate to grow biofilm. The dentin blocks were submerged into solutions for 5 min. The antimicrobial activity was evaluated by means of the adenosine triphosphate (ATP) assay and confocal laser scanning microscopy (CLSM). Fibroblasts 3T3-L1 (ECACC 86052701) were used to test the cytotoxicity of irrigating solutions. The antibiofilm effects determined by the ATP assay showed that 4% IBP-arginine solution exerted the highest antibiofilm activity, followed by 4% DCS and 4% IBP, with statistical differences among groups (p < 0.001). As for CLSM, 4% DCS and 4% IBP-arginine solutions gave the lowest viable cell percentages, without significant differences between them. Cytotoxicity results at 1/10 dilution were similar for all solutions. At 1/100 dilution, a 4% DCS solution obtained the lowest cell viability for both time periods assayed, 1 h and 24 h. The IBP-arginine group showed the highest cell viability at 24 h. In this preliminary study, in terms of antibiofilm activity and cytotoxicity, a mixed 4% IBP-arginine solution gave the most promising results. NSAID solutions could be recommendable drugs for endodontic disinfection procedures.

Influence of Genetic Polymorphisms on the Response to Tramadol, Ibuprofen, and the Combination in Patients With Moderate to Severe Pain After Dental Surgery

PurposeWe aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their mechanism of action. MethodsThe study population comprised 118 patients from a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. We analyzed 32 polymorphisms in the cytochrome P450 (CYP) enzymes COMT, ABCB1, SLC22A1, OPRM1, and SLC22A1. FindingsWe did not find any statistically significant difference among CYP2C9 phenotypes related to ibuprofen response, although CYP2C9 poor metabolizers had a longer effect (higher pain relief at 6 hours). Likewise, we did not find any statistically significant difference among PTGS2 genotypes, contradicting previously publications. ImplicationsThere was not a clear effect of CYP2D6 phenotype on tramadol response, although CYP2D6 poor metabolizers had a slower analgesic effect. Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels. Finally, we found a statistically significant better response in patients carrying the OPRM1 A118G G allele, which contradicts the previous reports. Measuring the active metabolite O-desmethyl-tramadol formation would be of great importance to better evaluate this association because O-desmethyl-tramadol has a higher μ-opioid receptor affinity compared with the parent drug. EudraCT.ema.europa.eu identifier: 2013-004637-33.

Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study

There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors' institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken. To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA. This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding. A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; p = 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; p = 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; p = 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects. These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen.

ObjectiveProstaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.Materials and methodsA randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation.ResultsAfter a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.ConclusionRapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.

Clinical Pharmacokinetics of Ibuprofen Arginine

Currently, several ibuprofen compounds are available on the market, mainly differing in terms of pharmaceutical composition that influence the pharmacokinetic profile and eventually the onset of drug action. This review will mainly deal with the clinical pharmacokinetics of ibuprofen arginine, an alternative formulation specifically designed to improve the absorption of ibuprofen. Indeed, available data from studies in healthy volunteers have consistently shown that the formulation of ibuprofen arginine is characterized by prompt absorption of ibuprofen as compared to the conventional formulation at all tested doses with higher peak plasma concentration and lower Tmax values. This trend has been confirmed also in studies dealing with chiral ibuprofen pharmacokinetics. Most importantly, the shortening in the absorption time observed either with racemic mixture or with the S(+)-enantiomer of ibuprofen arginine did not imply a faster drug elimination eventually leading to inadequate daily drug exposure, as documented by T1/2 and AUC values being comparable to those measured with the free acid form. Taken together, the pharmacokinetic/dynamic characteristics of ibuprofen arginine can be considered particularly favorable for several clinical conditions, such as moderate/severe pain, in which a rapid pharmacologic effect is required.

Ibuprofen–arginine generates nitric oxide and has enhanced anti-inflammatory effects

Ibuprofen, a chiral non-steroidal anti-inflammatory drug chemically related to fenoprofen and naproxen, has moderate but definite anti-inflammatory, analgesic and antipyretic properties, with considerably less gastrointestinal adverse effect than other drugs in the same family. Currently available in the market are preparations in which bioavailability of ibuprofen is increased by salification with various salts. We have investigated the pharmacological properties of one such salt, ibuprofen–arginine, of biological interest because l-arginine acts as substrate of the nitric oxide (NO) synthesising enzymes. Using epithelial HeLa cells expressing the endothelial NO synthase we show that ibuprofen–arginine releases NO and that this NO protects against the cytotoxic apoptogenic effects of staurosporine. We also found that ibuprofen–arginine is endowed with enhanced anti-inflammatory effects with respect to ibuprofen, as shown by reduced hind paw oedema, neutrophil infiltration and chondrocyte apoptosis in collagen-induced mouse arthritis, a model of chronic inflammation. NO has pleiotropic beneficial effects that may contribute to limit inflammation and anti-inflammatory compounds able to release NO display higher efficacy than the parent drugs in defined clinical settings. Our results open the possibility that NO generation contributes to the enhanced anti-inflammatory effects of ibuprofen–arginine vs. ibuprofen, suggesting co-administration of anti-inflammatory drugs and arginine as an additional way to exploit the beneficial effects of NO.

Ibuprofen arginine for pain control during scaling and root planing: a randomized, triple‐blind trial

The aim of this controlled clinical trial was to investigate the analgesic efficacy and tolerability of ibuprofen arginine in patients with mild-to-moderate periodontitis during and after non-surgical periodontal treatment. This randomized, triple-blind, placebo-controlled, parallel-group trial assessed the analgesic efficacy of ibuprofen arginine (Spedifen) in patients undergoing routine periodontal scaling and root planing. 64 patients with chronic periodontitis received either 800 mg ibuprofen arginine or placebo 30 min. before treatment. Numeric pain and electronic visual analogue scales ranging from 0 to 100 were used. The average pain levels during treatment were lower following ibuprofen arginine (quartiles: 0.5, 4.5, 11) compared with placebo (4, 16, 26), corresponding to a percentage reduction in median pain of 72% (p=0.023). The median maximum pain was 28 (inter-quartile range 10-50) following placebo and 10 (4-31) following ibuprofen arginine (p=0.065). In patients with mild-to-moderate chronic periodontitis, ibuprofen arginine was safe and superior to placebo for alleviating pain during non-surgical periodontal treatment. Its painless administration and rapid onset of action make it well suitable for pain management in a general dental office.

Efficacy and Safety of Ibuprofen Arginine in the Treatment of Primary Dysmenorrhoea

The aim of this study was to evaluate the efficacy and safety of ibuprofen arginate in the treatment of patients with primary dysmenorrhoea in normal clinical practice. In this open trial, patients received an initial oral dose of ibuprofen arginine 600mg at the onset of pain, followed by the same dose every 6 hours, if necessary, with a maximum daily dose of 2400mg. The study assessed the evolution of pain intensity, rapidity of action, need for supplementary analgesics, decrease in working or school hours lost, and safety and tolerability of ibuprofen arginine treatment. Each patient was evaluated prior to inclusion in the study and after one and three cycles. From the 1093 recruited patients, 854 women were evaluable for safety and tolerability, and 838 for efficacy. Significant improvement in pain relief was observed 15 minutes after treatment compared with baseline values (p < 0.001). At 15 and 30 minutes the percentage of patients reporting a marked decrease in pain intensity was 82.2% and 97.6%, respectively. Additionally, a significant reduction in absenteeism from work or school (from a mean of 4.6-0.8 hours per cycle) was observed (p < 0.001). Thirty-eight patients presented with adverse events in the trial period, but only 26 subjects (3% of 854) in the adverse events cohort reported having a possible adverse event, with gastrointestinal complaints being the most frequent. Ibuprofen arginine appears to be effective, fast, safe and well tolerated in the treatment of patients with primary dysmenorrhoea.

A comparison of ibuprofen arginine with morphine sulphate for pain relief after orthopaedic surgery

A comparison of ibuprofen arginine with morphine sulphate for pain relief after orthopaedic surgery

Ibuprofen Arginine vs Naproxen Sodium as Prophylactic Oral Treatment of Pain Due to Dental Surgery

139 patients due to undergo surgery for the removal of an impacted third molar were enrolled in a multicentre, randomised, double-blind, double-dummy, placebo-controlled study to compare the efficacy and tolerability of a new formulation of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, ibuprofen arginine, with those of naproxen sodium in the prophylaxis of pain. Each drug was administered as a single oral dose 15 minutes before surgery. Postoperative pain intensity was assessed on a Visual Analogue Scale (VAS) at fixed time-points after surgery, and patients completed a global assessment of efficacy at the end of the study.

Comparative Efficacy of Ibuprofen Arginine and ??-Cyclodextrin Piroxicam as Treatment for Tension-Type Headache

In this single-centre double-blind crossover trial, 30 patients with recurrent tension-type headache were randomised to single dose treatment with ibuprofen arginine, β-cyclodextrin piroxicam, or placebo. Pain intensity was measured by the patient on a Visual Analogue Scale (VAS) from 0mm (no pain) to 100mm (unbearable pain) just before ingestion of the study medication (baseline) and at 15, 30, 60, 120, and 240 minutes thereafter.

Comparative Efficacy of Oral Ibuprofen Arginine and Intramuscular Ketorolac in Patients with Postcaesarean Section Pain

In this double-blind double-dummy placebo-controlled study. 92 patients from a single centre were randomly assigned to receive either ibuprofen arginine 400mg orally, ketorolac 30mg by intramuscular injection, or placebo, after caesarean section. Pain intensity was measured on a Visual Analogue Scale (VAS) ranging from 0 (no pain) to 100mm (unbearable pain) at 15, 30, 45, 60. 90, 120, 180, 240, 300, and 360 minutes after the administration of study medication.

Clinical Efficacy of Ibuprofen Arginine in the Management of Postoperative Pain Associated with Suction Termination of Pregnancy

This randomised parallel group double-blind placebo-controlled study was carried out to assess the analgesic efficacy of preoperatively-administered oral ibuprofen arginine 400mg in the management of postoperative pain after suction termination of pregnancy. 75 patients, aged between 16 and 45 years, were evaluated according to their own assessment of pain on a 100mm Visual Analogue Scale (VAS) with extremes at either end of ‘no pain’ (0mm) and ‘unbearable pain’ (100mm). Responses were recorded for each patient 30 minutes before surgery (baseline) when the trial medication was administered, and at specified time-points up to 4 hours after the procedure.

Comparative Efficacy of Oral Ibuprofen Arginine and Intramuscular Ketorolac in Patients with Postoperative Pain

The comparative clinical efficacy and tolerability of ibuprofen arginine and ketorolac were determined in a study that used a double-blind double-dummy protocol. 124 patients who underwent surgical repair of inguinal hernia at a single medical centre were randomly assigned to receive either oral ibuprofen arginine 400mg, ketorolac 30mg by intramuscular injection or placebo. Pain intensity was assessed at baseline and at 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 minutes after medication administration, on a Visual Analogue Scale (VAS) ranging from no pain (0mm) to unbearable pain (100mm).