Ketorolac Research Articles

Influence of anti-inflammatory irrigant on substance P expression for single-visit root canal treatment of teeth with irreversible pulpitis.

One of the main objectives of root canal treatment is to alleviate the pain associated with irreversibly inflamed pulps. However, some patients may have moderate to severe pain following treatment. The aim of this study was to compare and assess the effect of ketorolac tromethamine on substance P expression in the pulp and periapical tissues when used as a root canal irrigant for single-visit root canal treatment in teeth with irreversible pulpitis. Thirty-six patients were randomly allotted to three irrigant groups - saline (n=14), 3% sodium hypochlorite (n=11) and ketorolac tromethamine (n=11). Pulp blood samples (S1) were collected on gaining access to the pulp, and periapical blood samples (S2) were collected after root canal preparation. Quantification of substance P was done by ELISA test. The ketorolac tromethamine group had greater reduction in substance P expression (S2). Post-operative pain levels were not significantly influenced by the different root canal irrigants.

Influence of different irrigants on substance P and IL-8 expression for single visit root canal treatment in acute irreversible pulpitis.

The aim of this study was to assess the influence of ketorolac tromethamine and dexamethasone on substance P and IL-8 expression when used as a root canal irrigant for single visit root canal treatment for acute irreversible pulpitis. A total of 42 patients with pain due to acute irreversible pulpitis in carious premolar and molar teeth were included in this study. The four irrigation groups were as follows: saline (n=11), 3% sodium hypochlorite (n=11), ketorolac tromethamine (n=10) and dexamethasone (n=10). Blood samples S1 and S2 were collected upon access opening and after canal preparation, respectively. Quantification of substance P and IL-8 were done using ELISA test. Post-operative pain was assessed by questioning the patients. The difference between S1 and S2 sample values for the four different irrigant groups was not significant. The sodium hypochlorite group had a higher mean expression of substance P and IL-8 values. Dexamethasone irrigation was more effective in controlling post-operative pain.

CdS-Decorated MIL-53(Fe) Microrods with Enhanced Visible Light Photocatalytic Performance for the Degradation of Ketorolac Tromethamine and Mechanism Insight

Metal–organic frameworks (MOFs) are extensively employed for environmental remediation due to their outstanding physical and chemical properties. Herein, we have demonstrated the complete and simpl...

Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drug classes worldwide. Although, these drugs have a potent analgesic and anti-inflammatory effects associated with nephrotoxicity. Factors such as advanced age and comorbidities may contribute to increase the risk of NSAID-related nephrotoxicity. The current study was designed to study the dual effect of non-NSAIDs and anticoagulants on the rat kidney.MethodsThirty-two adult male albino rats were divided into four groups (n = 8): first, served as the control group which was orally administered with distilled water; second, served as the ketorolac (KT) group which received a daily intramuscular injection of ketorolac tromethamine (3 mg/kg/day); third, served as the warfarin (WR) group which was orally administered with racemic warfarin (0.3 mg/kg/day); and fourth, served as the combined (KT/WR) group which received an oral administration of WR (0.3 mg/kg/day) followed by an intramuscular injection of KT (3 mg/kg/day). After six consecutive days of daily treatment, all animals were sacrificed and their blood and tissue samples were collected.ResultsA significant decrease in serum level of creatinine was observed in WR- and KT/WR-treated groups. However, urea increased significantly in the serum of the combined group, KT/WR. Furthermore, both WR- and KT/WR-treated groups showed a significant increase in malondialdyhed (MDA) level; however, WR treatment induced a significant decrease in reduced glutathione (GSH) level. The total antioxidant capacity (TAC) of rat kidney showed a significant decrease in all treated groups. Electron microscopic investigations of kidney cortex localized variable degrees of focal degeneration, vacuolation, and vascular congestion in KT- and WR-treated groups that are more vigorously attacking the cortical tissues in KT/WR-treated rats.ConclusionsWe can conclude that the combined therapy of anti-inflammatory and anticoagulant drugs must be avoided or at least minimized, particularly in the elderly people, who mostly had other complications, in order to avoid the severe side effects on kidney structure and function.

Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery.

To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk. Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. SCTA appears to be an effective alternative to prolong postoperative topical steroid use.

A simple randomized comparative study to evaluate the efficacy of 0.7% w/v Olopatadine hydrochloride ophthalmic solution and the Fixed Dose Combination of 0.1% w/v Olopatadine hydrochloride and 0.4% w/v Ketorolac tromethamine ophthalmic solution for the

A simple randomized comparative study to evaluate the efficacy of 0.7% w/v Olopatadine hydrochloride ophthalmic solution and the Fixed Dose Combination of 0.1% w/v Olopatadine hydrochloride and 0.4% w/v Ketorolac tromethamine ophthalmic solution for the

Extended delivery of non-steroidal anti-inflammatory drugs through contact lenses loaded with Vitamin E and cationic surfactants

The purpose of this study is to extend drug release from ACUVUE Oasys® and ACUVUE TruEye® silicone hydrogel contact lenses by incorporation of vitamin E in conjunction with a cationic surfactant. In ACUVUE Oasys® and ACUVUE TruEye®, the release of ketorolac tromethamine and flurbiprofen sodium is extended from hours to several days for 11% and 21% vitamin E, (weight of vitamin E / weight of dry lens) but with a considerable reduction in the amount of drug released. Cetalkonium chloride and stearylamine increased the drug loading capacity which was otherwise compromised by the addition of vitamin E in the contact lenses. In the case of diclofenac sodium, a sustained release over 150 h for both contact lenses can be achieved. It was found that the release-time-increase factor due to vitamin E has a linear dependence with the octanol-water partition coefficient of the drug in ACUVUE Oasys®. The results in this study show that contact lenses loaded with vitamin E in conjunction with cationic surfactants achieved sustained release of non-steroidal anti-inflammatory drugs (NSAIDs) within the therapeutic window.

Paravertebral Dexmedetomidine in VideoAssisted Thoracic Surgeries for Acute and Chronic Pain Prevention

Background: Video-assisted thoracoscopic surgery (VATS) is considered as one of the minimally invasive surgeries. Early postoperative pain alleviation is very important to avoid complications, at the same time, proper early pain control is an established fact to decrease the incidence of chronic pain. Objectives: To evaluate the efficacy of thoracic paravertebral block (PVB) by a bupivacaine/ dexmedetomidine mixture on acute and chronic post-thoracoscopic surgery pain in patients undergoing VATS. Study Design: A randomized prospective double-blinded trial. Setting: Assiut University Hospitals, Orman Cardiology Hospital. Methods: Sixty adult patients underwent elective VATS surgery under general anesthesia randomly allocated into 2 groups; Group I received thoracic PVB with isobaric bupivacaine 0.5% (0.3 mL/ kg) and Group II received PVB with isobaric bupivacaine 0.5% (0.3 mL/kg) and dexmedetomidine (1 mcg/kg). Postoperative pain (at rest, with cough, and with movement) was assessed through a visual analog scale (VAS) every 30 minutes in the first 2 hours, then at the second, fourth, eighth, and 24th hours. Time to first analgesia request and consumption of intravenous rescue analgesia (ketorolac tromethamine 30 mg/dose) was recorded. Follow-up of the patients regarding the incidence of chronic post-thoracoscopic pain by the end of the third and sixth months after the procedure was reviewed through the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale. Results: VAS score was significantly lower in Group II during the early postoperative 90 minute records. Pain with cough and with movement persisted to be significantly lower in Group II up to the second postoperative hour. Time to first analgesia requirement was significantly longer in Group II in comparison to Group (P < 0.001). There was less ketorolac consumption in Group II than in Group I (P = 0.002). At the third month, Group II showed significantly lower incidence of LANSS pain scale than Group I (P = 0.04). Limitations: There was the heterogeneity of surgical procedures in the patients. Conclusions: Dexmedetomidine as an adjuvant to bupivacaine PVB offers better pain relief during the early postoperative hours, and it carries a favorable effect on chronic postoperative pain. Clinical trial registry number: NCT03632161. Key words: Dexmedetomidine, paravertebral block, video-assisted thoracoscopic surgery, postoperative pain, chronic pain

STUDIES ON EFFECT OF FORMULATION AND PROCESSING PARAMETERS ON STABILITY OF KETOROLAC TROMETHAMINE ORALLY DISSOLVING FILMS

Objective: The objective of the proposed work was to study the effect of various formulation and process parameters of solvent casting method on the physical and chemical stability of Ketorolac Tromethamine (KT) in the orally dissolving film dosage form.
 Methods: KT-excipient interaction study was carried out both in solid state and by processing samples through the solvent casting technique. The samples were evaluated using IR spectroscopy (IR) and X-ray diffractometry (XRD). Solvent casting method was used to prepare KT films using different film-forming polymers, and solvents. The drying temperature and pH of the dispersion were also varied to study the effect of these parameters on the stability of KT. All the formulations were analysed chemically initially and after one month of storage at 40 °C/75% RH.
 Results: During KT-excipient interaction study in solid state KT was found to be stable. No significant changes were observed in its impurity profile. Interaction between different polymers and KT was observed after the solvent casting process as revealed by IR and XRD analysis. The interaction was further confirmed in the film formulations upon chemical analysis. The polymers showing interaction with KT in XRD and IR were making it unstable chemically and were responsible for its chemical degradation as revealed by chemical analysis. It was also revealed that KT is most stable when processed using water as the solvent. KT was found to be stable when processed at a higher temperature and at acidic pH during film formation. It was found that chemical stability is more when Polyethylene oxide (PEO) and water under acidic pH are used and films are dried at a higher temperature.
 Conclusion: Both formulation parameters and processing conditions of the solvent casting technique affects the stability of drugs and hence should be studied as part of pre-formulation studies while developing orally dissolving films of drugs.

Formulation and pharmacopoeial quality evaluation of ketorolac tromethamine IR tablet and comparison with marketed product

Formulation and pharmacopoeial quality evaluation of ketorolac tromethamine IR tablet and comparison with marketed product

ANALGESIA FOR AGED AND GERIATRIC PATIENTS DURING CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS

Balanced perioperative multimodal analgesia using multiple synergistic agents minimizes side effects that can be caused by high doses of only one aesthetic agent. The aim of the work was to determine the efficacy of perioperative multimodal low-opioid analgesia as anesthetic assurance techniques in aged and geriatric patients during cardiac surgery with cardiopulmonary bypass.Materials and methods. The study included 18 patients (11 (61.1%) men and 7 (38.9%) women) aged from 63 to 76 years old (mean age 69.5±6.2 years), who underwent coronary artery bypass grafting with cardiopulmonary bypass support. The average body weight was 89.6±13.9 kg (75 to 115 kg). The anaesthesia consisted of intravenous (iv) administration of propofol in a dose of 1.52±0.05 mg/kg and fentanyl in a dose of 1 μg/kg. Muscle relaxation was achieved by injecting pipecuronium bromide in a dose of 0.1 mg/kg. Sevoflurane inhalation was used to maintain anesthesia. Before making incision, the subnarcotic dose of ketamine (0.5 mg / kg) and lidocaine 1 mg/kg bolus were added with simultaneous administration of the continuous infusion of the latter in a dose of 1.5-2 mg/kg per hour. For postoperative analgesia ketorolac tromethamine was used. The intensity of the pain syndrome was assessed using a 10-point visual-analog scale of pain. The level of endocrine-metabolic response was determined by measuring the dynamics of lactate and cortisol.Results. The average dose of fentanyl, which was used for the patient during the whole time of anaesthesia, was 1.09±0.03 μg / kg per hour (on average 358.3±27.1 μg for all time of surgery). During the extracorporeal circulation and in the early postoperative period, the blood circulation parameters in all patients examined corresponded to the hemodynamic profile of the operated pathology. Positive verbal contact with patients was recorded in 18.6±3.4 minutes after the end of anaesthesia. The level of cortisol in the early postoperative period was 479.3±26.4 nmol/l. The average values of the intraoperative level of lactate were 1.61±0.2 mmol/l. The mean pain level in the first postoperative day in the examined patients was 4.6 ± 1.2 (3-6) scores by VAS, one day after the operation – 2.6±1.1 (1.5-4) scores by the VAS.Conclusions. Multimodal low-opioid analgesia provides an adequate analgesic effect in aged and geriatric patients that is confirmed by the absence of hemodynamic and endocrine-metabolic disorders. The use of ketorolac as a component of multimodal low-opioid analgesia is an effective method for achieving adequate postoperative analgesia and contributes to reducing the side effects associated with the use of narcotic analgesics.

The role of ketorolac in the accelerated rehabilitation program for patients in outpatient surgery

The paper presents the basic principles of accelerated reabiletacii patient in the practice of ambulatory surgery. Pathophysiological mechanisms revealed organism response to surgical trauma. Pain, as a powerful trigger of surgical stress response due to neurohumoral, endocrine, immune, Hemostatic and metabolic mechanisms largely determines the results of surgical treatment. The most commonly used ketorolac (Ketanov) having the form parenteralnuju. The summary of the application of both drug ketorolac argued with pronounced analgesic effect. Intra-operative use of ketorolac is justified, as the drug reduces the total dose of anesthetics and Narcotic analgesics. Improving the quality of postoperative analgesia has predetermined creation protocol analgesia, as basic drugs used non-steroidal anti-inflammatory drugs.

Dual release of an antibiotic and anti-inflammatory from intraocular lenses for prophylaxis of endophthalmitis

Introduction: Cataract is the leading cause of blindness and affects more than 20 million people worldwide each year. It is treated by replacing the opacified crystalline lens with an implantable synthetic lens. Although considered as a very safe procedure, cataract removal surgery has associated risks of post-surgical complications, such as endophthalmitis, a serious intraocular inflammatory disorder resulting from bacterial infection. Thus, in the post-operatory period, antibiotics and anti-inflammatories eye drops are administered with a frequent posology to prevent eventual complications. This drug delivery method is not very effective and may lead to low patient compliance. In this work, it is explored the possibility of using drug-loaded IOLs to ensure a simultaneous release of both antibiotic and anti-inflammatory drugs. Materials and methods: An antibiotic, moxifloxacin (MXF), and two anti-inflammatories, ketorolac (KTL) and diclofenac (DFN) were loaded in acrylic IOLs by soaking in drugs solutions at 60 °C for 2 weeks. The lenses were loaded in a double drug solution of MXF + KTL with a concentration of 5 mg/mL each drug and in MXF + DFN with a concentration of 1.11 mg/mL for MXF and 0.56 mg/mL for DFN due to drugs solubility constrains. Single load of the drugs (with the same concentrations) was also carried out for comparison purposes. Both double loaded lenses were sterilized by autoclaving (121 °C, 1bar, 1h). In vitro drug release experiments were performed in sink conditions. The effect of the drug loading and of the sterilization on lenses properties such as the swelling capacity, optical properties (transmittance) and mechanical properties (Young’s modulus) were evaluated. A mathematical model was applied to predict the in vivo efficacy of the drug release profile. Results: It was observed that the double loaded lenses released a significant higher amount of each drug than the single loaded lenses, with the exception of DFN, which release remains the same when double or single loaded. The devices should be able to release effective amounts of each drug for 2-4 weeks. Sterilization by autoclaving almost did not affect the drug release profile of the double loaded lenses. It was found that the presence of drugs increases the swelling capacity of the lenses: the lenses soaked in MXF + KTL swelled more 50% than the lenses hydrated in saline solution, while in MXF + DFN swelled more 15%, independently of being sterilized or not. Concerning the optical and mechanical properties, the changes observed do not compromise the use of the lenses. Discussion and conclusions: The sterilized and double loaded lenses comply with both antibiotic and anti-inflammatory therapeutic needs for the prophylaxis of endophthalmitis after cataract surgery, keeping adequate optical and mechanical characteristics. They may be considered a promising alternative to the commonly used drug administration route in the post-operatory period.

Effect of sterilization by steam and pressure and gamma radiation on drug-loaded intraocular lenses for prophylaxis of endophthalmitis

Introduction: Cataracts surgery involves the removal of the opacified natural lens and implantation of an intraocular lens (IOL). However, in the post-operatory period, complications such as endophthalmitis can appear. To prevent this, antibiotics and anti-inflammatories are administered in eye drops with a very frequent posology. This drug delivery method leads to a low bioavailability of the drugs in the eye and seldom to low patient compliance. To overcome these problems, it has been explored the possibility of using drug-loaded IOLs. Since IOLs are place inside the eye, sterilization is mandatory. Although there are some sterilization methods well-defined, some concerns are raised about their effects on drug loaded systems. In this work the effect of two common sterilization methods (steam and pressure and gamma radiation) on IOLs properties and on the drug release from drug-loaded IOLs is investigated. Materials and methods: Acrylic IOLs with 26% of swelling capacity, an antibiotic, moxifloxacin (MXF), and two anti-inflammatories, ketorolac (KTL) and diclofenac (DFN) were used. First, it was studied the effect of sterilization on the lenses properties such as the swelling capacity, optical properties (transmittance) and mechanical properties (Young’s modulus). Then, the drugs were loaded into the IOLs by soaking (5 mg/mL) at 60 °C for 14 days and the effect of sterilization in the release of the drugs was evaluated. In vitro drug release experiments were carried out in sink conditions. Two methods of sterilization were experimented: steam and pressure by autoclaving (121 °C, 1bar, 1h) and gamma radiation (25 kGy, rate 2.5 kGy/h). For steam and pressure the lenses were sterilized hydrated in the 1st day or in the last day of loading (14th day). For gamma radiation the lenses were sterilized in dried state, due to degradation of drugs by gamma radiation when in aqueous solution. In this case, sterilization was carried out after 14 days of loading and 7 days of vacuum drying. A mathematical model was applied to predict the in vivo efficacy of the drug release profile for the best system. Results: Regarding the effects on the lenses properties, sterilization by autoclaving slightly increased the Young’s modulus, while gamma radiation slightly increased the transmittance in the 400-500 nm region. However, the observed changes do not compromise the use of the lenses. Concerning the drug-loaded lenses, it was observed that although steam and pressure done in the 1st day of loading does not affect the release of the drugs, when done in the 14th day decreases significantly the amount of drug release for all three drugs. Gamma radiation slightly increased the released amount only for lenses loaded with MXF. The application of the mathematical model suggests that the steam and pressure sterilized lenses at 1st day comply with the therapeutic needs. Discussion and conclusions: Sterilization by steam and pressure when done in 1st day of loading or gamma radiation after loading and drying can be used as sterilization methods, since they do not affect significantly the lenses properties or the drugs release. As the IOLs are generally used in hydrated state at the time of the surgery, steam and pressure is the ideal sterilization method for drug-loaded IOLs.

Generation of sustained release chitosan nanoparticles for delivery of ketorolac tromethamine: a tubular microreactor approach

Sustained release ketorolac tromethamine (KT) loaded chitosan nanoparticles were generated using tubular microreactor with syringe pump. 32 full-factorial design was employed for the optimization of formulation parameters. The chitosan concentration (X1) and cross-linking agent concentration (X2) was designated as the independent variables while drug release (Y1) and encapsulation efficiency (Y2) was selected as dependent variables to achieve desired entrapment efficiency and sustained drug release. The obtained nanoparticles were evaluated for particle size, field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRD), encapsulation efficiency and in vitro drug release study. Scanning electron microscopy of optimized run showed that the nanoparticles are spherical, and the particle size distribution of nanoparticles were found in the range of 164.2–255 nm. An encapsulation efficiency was obtained between 76% - 96%. Based on in-vitro drug release study, KT loaded chitosan nanoparticles exhibited sustained release action over a period of 12 h. An application of in-vitro drug release statistics to numerous kinetic equations designated that the diffusion (Higuchi model) of drug was responsible for drug release.

Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies

Objectives: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK).Significance: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers.Methods: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits.Results: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75 ± 0.64 to 498.95 ± 0.64 nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96–77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN® and Ketoroline®).Conclusions: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.

Comparative Study Of The Effect Of Topical Corticosteroid With Non-Steroidal Anti Inflammatory Agents On Post-Operative Inflammation And Corneal Astigmatism After Cataract Surgery.

Purpose:To compare the effects of topical corticosteroid with non-steroidal anti-inflammatory agents on postoperative control of inflammation, pain and corneal astigmatism.
 Setting: Indira Gandhi Government General Hospital & Postgraduate Institute, Puducherry.
 Methods:A prospective comparative study in two hundred patients with visually significant cataract, undergoing manual small incision cataract surgery with implantation of posterior chamber intraocular lens were randomly assigned into four groups with minimum 50 patients in each. All cases of uncomplicated cataract surgery were assigned to following groups to receive one of the following topical anti-inflammatory agents as postoperative medications: Group A- 1% predinsolone acetate, Group B -0.5% ketorolac tromethamine, Group C 0.09% Bromfenac eye drops, Group D 0.1% Nepafenac eye drops. All patients were examined on 1 day (baseline), 3th day, 5th day, 7th day, 14th day and 1month after surgery for assessment of ocular pain, anterior chamber cells and flare and corneal astigmatism.
 Results:The cells and flare were least in bromfenac group on the 3rd postoperative day.Nepafenac is effective in inflammation control from 5th postoperative day. There was a significant association of use of drug and severity of ocular pain upto 1stpostoperative week. There was statistically significant difference between NSAIDs and steroid on postoperative astigmatism (P <0.001).
 Conclusions:Bromfenac is effective as an anti-inflammatory agent in the immediate postoperative period. All the NSAIDs are found to be as effective as steroid after 1 week onwards. The NSAIDs showed reduced astigmatism changes and stabilizes astigmatism much quicker than steroids.

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies.

Ketorolac (KTR) is used as an analgesic drug with an efficacy close to that of the opioid family. It is mainly used for the short term treatment of post-operative pain. It can inhibit the prostaglandin synthesis by blocking cyclooxygenase (COX). In this investigation, the inherent stability and biochemical interaction of Ketorolac (KTR) and its degradation products have been studiedon the basis of quantum mechanical approaches. Density functional theory (DFT) with B3LYP/ 6-31G (d) has been employed to optimize the structures. Thermodynamic properties, frontier molecular orbital features, dipole moment, electrostatic potential, equilibrium geometry, vibrational frequencies and atomic partial charges of these optimized structureswere investigated. Molecular docking has been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to search the binding affinity and mode(s). ADMET prediction has performed to evaluate the absorption, metabolism and carcinogenic properties. The equilibrium geometry calculations support the optimized structures. Thermodynamic results disclosed the thermal stability of all structures. From molecular orbital data, all the degradents are chemically more reactive than parent drug (except K3). However, the substitution of carboxymethyl radicalin K4 improved the physicochemical properties and binding affinity. ADMET calculations predict the improved pharmacokinetic and non-carcinogenic properties of all degradents. Based on physicochemical, molecular docking, and ADMET calculation, this study can be helpful to understand the biochemical activities of Ketorolac and its degradents and to design a potent analgesic drug.

ELECTROCHEMICAL DETERMINATION OF KETOROLAC - A NON-OPIOID ANALGESIC AT GLASSY CARBON ELECTRODE

Objectives: The study has been carried to investigate the electro-oxidation mechanism and to develop a selective and sensitive method for determination of ketorolac (KTL), a non-opioid analgesic drug,.Methods: A simple electro analytical method was used for the determination of ketorolac (KTL) using glassy carbon electrode by cyclic and differential pulse voltammetric techniques (DPV). The effect of various experimental parameters such as accumulation time, pH, scan rate, on the voltammetric responses of KTL was evaluated.Results: In the optimized conditions, variation of peak current with respect to concentration was studied and the calibration curve of the peak current vs. KTL concentration was drawn with a linear range of 10- 350 μM with an excellent detection limit of 8.08×10-8 M. This method was successfully tested for the determination of KTL in pharmaceuticals and human urine samples.Conclusion: From the results, it was observed that, the selected method is rapid, sensitive and low cost.

Abstract P1-20-01: Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical trial

Abstract Introduction: Perioperative events may affect the risk of breast cancer recurrence after surgery. Ketorolac, a non-steroidal anti-inflammatory drug routinely used to improve pain control postoperatively has been associated with better breast cancer outcome in retrospective studies. However, it is still unknown whether a single dose of pre-incisional ketorolac may be sufficient to prolong recurrence-free survival. Patients and methods: The KBCt trial (NCT01806259) is a national, multicenter, prospective, double-blind, placebo-controlled, randomized phase III trial in high risk breast cancer patients. Each patient was assigned to the ketorolac or the placebo group. Patients were given one dose of ketorolac tromethamine (Taradyl®, N.V. Roche S.A., Belgium) or a matching placebo 30 minutes before surgery. Eligible patients were ≥18 and ≤75 years old with histologically or cytologically confirmed, invasive ductal or lobular breast carcinoma planned for curative breast cancer surgery, and with at least one of these 3 criteria: a Neutrophil-to-Lymphocyte Ratio ≥4, node-positive disease (cN1-N3) or a triple-negative histology. The primary endpoint of the study was Disease-Free Survival (DFS). Secondary endpoints included safety, pain assessment and overall survival. Results: Two hundred and three patients were assigned to ketorolac (n=96) or placebo (n=107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD 14) years. Both intra- and post-operative blood losses were not different between groups and there was no difference in pain at day 1 after surgery. There was no difference between the 2 arms for DFS (p=0.52) nor for OS (p=0.88). Discussion and conclusion: This study shows that a single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival is also comparable. No safety concerns were observed in this study. Citation Format: Berliere M, Bouche G, Duhoux F, Coulie P, De Cloedt J, Dekleermaker A, Guillaume J-E, Ledent M, Machiels J-P, Mustin V, Swinnen W, Vander Essen L, Van Maanen A, Verougstraete J-C, De Kock M, Forget P. Intraoperative ketorolac in high-risk breast cancer patients with and without inflammation. A prospective, randomized, placebo-controlled clinical trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-20-01.