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(S)-Ketoprofen plasma concentration versus time profile after oral administration of 3.2 mg/kg of (S)-ketoprofen or 3.2 mg/kg of (S)-ketoprofen þ 17.8 mg/kg of caffeine to male Wistar rats. Each point represents the mean value + SEM of six animals.
Source publication
A fast and reproducible high-performance liquid chromatography method has been developed for the determination of (R)- and (S)-ketoprofen. Ketoprofen enantiomers were determined in plasma samples (50 µL), after solid-phase extraction, using diclofenac
as internal standard. Analyses were performed on a (S, S)-Whelk-O 1 stainless steel column (5 µm,...
Context in source publication
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Citations
... Due to specificity in its action KP when orally administered is absorbed before coming to colon, (Xi et al., 2005) its absorption from intestine is rapidly occurred and eliminated mainly by metabolism and urinary excretion conjugated with glucuronic acid and it is also thought that KP usually acts by inhibiting the synthesis of prostaglandins (Misra and Kishore, 2013) Residence time of this drug in stomach is usually associated with different behavioral and physiological factors like smoking, sex amount and mode of administration. (Magallanes et al., 2016) Various analytical methods involving the use of capillary electrophoresis, (Li et al., 2003;Samakashvili et al., 2013;Zhou and Li, 2004), High-performance liquid chromatography (Assaf et al., 2017;Eichhold et al., 2000;Jedziniak et al., 2010;Lopez-Munoz et al., 2014;Patrolecco et al., 2013;Ye and Yu, 2003), isotopic dilution or capillary electrophoresis, capillary chromatography (Macià et al., 2006) or Liquid chromatography with multiple detectors like UV diode array, spectrofluorimetric detectors (Santos et al., 2005) have been followed for the determination of KP. Though, LC-MS methods for the determination of KP propose more sensitive and robust quantification these instruments are either costly or very complex for routine analysis like kinetics studies or toxins screening (Hložek et al., 2014). ...
A convenient and Rapid High-performance Liquid Chromatography (HPLC) based protocol was optimized for the routine analysis and kinetics study of Ketoprofen (KP) in plasma and urinary execration of patients. The optimized HPLC method was found to be linear over the wide range of KP concentration (1-90 µg/mL) with substantial recovery rates (95.5-97.63%) of calibration standards at an improved detection (0.02 μg/mL LoD) and quantitation limit (0.06 μg/mL LoQ) and acceptable inter and intraday variability (RSD≤ 7.75 %). The maximum amount (μg/mL) of KP was excreted via the urine of all participated patients during the first two hours (h) of oral administration. Likewise, a fast depletion in blood plasma concentration started early after oral administration. Overall, the present method provided a convenient, rapid and reliable solution for the routine analysis and kinetic study of KP in biological samples.
... Extraction of (S)-ketoprofen from plasma samples was conducted using a solid-phase extraction (SPE) technique previously developed in our laboratory [31]. Briefly, the cartridges (Strata-X 33 µm polymeric reversed phase cartridge, Phenomenex, Torrance, CA, USA) with the aid of a vacuum device (Vac-Elut, Speed Mate 10, Applied Separations Inc., Allentown, PA, USA) were preconditioned by flushing with 2 mL of methanol and 1 mL of high-performance liquid chromatography (HPLC) water. ...
... (S)-ketoprofen plasma concentrations were determined by HPLC analysis with ultraviolet (UV) detection [31]. The chromatographic system consisted of a Perkin Elmer Series 200 HPLC (Norwalk, CT, USA) equipped with a binary pump, a manual injector with a 20 µL loop, and a variable wavelength UV 785 model detector (Applied Biosystems, Foster, CA, USA). ...
... In humans, rats, and mice, absorption is not stereoselective [35]. The pharmacokinetics of (S)-ketoprofen alone and in combination with caffeine have been previously determined in other studies [31]. After administration of a single dose of 3.2 mg/kg of (S)-ketoprofen or 3.2 mg/kg of (S)-ketoprofen + 17.8 mg/kg of caffeine to Wistar rats, significant differences in C max and AUC 0-∞ of (S)-ketoprofen were found (p < 0.05). ...
The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in Cmax, AUC0-24, and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action.
... Carefully monitoring the action of NSAIDs is therefore crucial with a view to improving the toxicological management of logn-term NSAIDs therapies. A number of High performance liquid chromatography (HPLC) [4][5][6] and capillary electrophoresis [7,8] methods for the determination of KET enantiomers in biological fluids [9]. ...
Ketoprofen (KET) is an active pharmaceutical compound that has pain relieving and antipyretic effects. Its determination in body fluids and environmental waters is important due to widespread use of the compound. In this study, a selective and reliable method has been developed for the determination of ketoprofen in water and artificial serum using molecularly imprinted polymers (MIPs) as a solid phase extraction sorbent prior to HPLC-DAD detection. The MIP was synthesized by copolymerization of methacrylic acid (MAA) and trimethylpropane trimethacrylate (TRIM) in the presence of ketoprofen as the template. For the sake of comparison, nonimprinted polymer (NIP) was also synthesized under the same experimental conditions without the addition of ketoprofen under the same experimental conditions. Critical extraction parameters such as sample pH, shaking time and sorbent amount were optimized and adjusted to 8.0, 24 h, and 10.0 mg, respectively, for a sample volume of 10.0 mL. MIP showed higher selectivity than NIP towards ketoprofen in an artificial matrix containing another pain relieving drug, ibuprofen, and a cardiovascular drug, metoprolol. The proposed method was successfully applied for the detection of ketoprofen in spiked drinking water, tap water, and artificial serum samples, and showed satisfactory results with respective recoveries of 96.8 % (± 0.8), 93.7% (± 0.6), 62.2% (± 0.6), and 69.9% (± 0.6).
Introduction
Ketoprofen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Side effects of ketoprofen occur mainly from the gastrointestinal tract due to the inhibition of cyclooxygenaze-1. Binge drinking at least once a week is reported by 80 million Europeans. On the day after many of them use NSAIDs. This increases the risk for damage of gastric mucosa.
Aim
The aim of the study was to check if use of ketoprofen lysine salt (KLS) has any gastroprotective effect on mucosa of rat stomach after ethyl alcohol intoxication.
Materials and methods
There were 6 groups of 6 male rats which received:
1.ethanol;
2.0.9% NaCl;
3.0.9% NaCl and ketoprofen;
4.ethanol and ketoprofen;
5.0.9% NaCl and KLS;
6.ethanol and KLS.
Results
In groups 1, 2 and 3 the histopathologic examination of the stomachs revealed normal picture, without signs of inflammation. In the group 4, 5 and 6 within the mucosa and submucosa there were visible numerous infiltrates of inflammatory cells, consisting mainly of lymphocytes, plasmocytes and eosinophilia. Total leukocyte count was elevated in group 3, 4, 6. There was a significant decrease of blood urea concentration in group 6 vs 2 and significant decrease of serum albumin in group 6 vs 1 and 2, and total protein vs group 1.
Conclusion
Side effects of ketoprofen occur mainly from the gastrointestinal tract. KLS has no gastroprotective effect after ethanol-gastric injury and does not protect gastric mucosa from damage produced by binge drinking. Therefore it should not be used after drinking distilled spirits.
Two non-steroidal anti-inflammatory drugs, ketoprofen and diclofenac sodium could be determined spectrofluorimetrically in their pure forms and different dosage forms using acriflavine reagent. It was found that the quenching of acriflavine fluorescence is going linearly with increasing the concentration over the ranges of 1.0-10.0 μg/mL for both ketoprofen and diclofenac sodium. The proposed method was studied to attain the optimum conditions with maximum sensitivity and precision without harming the environment. A proposal for the reaction mechanism was postulated depending on ion-association complex formation between acriflavine and each of the studied drugs in 1:1 ratio. International council of harmonization (ICH) guidelines were followed to validate the method. The lowest amount that could be detected by the proposed method is 0.28 and 0.48 μg/mL for both ketoprofen and diclofenac sodium, respectively. It was found that no significant difference between the proposed and comparison methods as indicated from the calculated statistical values.
The enantioselective analytical method for trace ketoprofen (KET) in human saliva was developed for the first time using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) combined with a derivatization using a chiral reagent, (S)‑1‑methyl‑4‑(5‑(3‑aminopyrrolidin‑1‑yl)‑2,4‑dinitro‑phenyl)piperazine (APy‑PPZ). The APy‑PPZ derivatization enabled highly sensitive detection (detection limit, 0.5 fmol on column) and complete separation with high resolution (Rs = 4.3) of KET enantiomers. The calibration curves of both KET enantiomers in saliva were linear in the concentration range of 5–500 nM. The developed method showed good analytical performance with relative standard deviations (RSDs) below 2.6% and good accuracy (100.5–105.9%) through intra- and inter-assay and gave a potential for practical application to the quantitative determination of KET in human saliva.
