Ibuprofen blood plasma levels and onset of analgesia

Mehlisch, Donald R.; Sykes, John

doi:10.1111/ijcp.12053

Cited by 29 publications

(16 citation statements)

References 26 publications

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“…Reported NSAID functions include inhibition of NF-κB, inhibition of proteasome function, activation of intrinsic and extrinsic pathways of apoptosis, cell cycle arrest, and activation of stress kinases (Jana, 2008; Leibowitz et al, 2014). However, many of these effects are seen only at superphysiological concentrations, limiting their biological relevance (Ghosh et al, 2015; Mehlisch and Sykes, 2013). Here, we have identified cysteine-aspartic proteases (caspases) as novel targets for some NSAIDs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations.…”

Section: Introductionmentioning

confidence: 99%

Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

Smith

Soti

Jones

et al. 2017

Cell Chemical Biology

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Summary Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID-family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX-independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design.

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Section: Introductionmentioning

confidence: 99%

Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

Smith

Soti

Jones

et al. 2017

Cell Chemical Biology

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“…The concentration of the test solution, 10 µg/ml, is correlated with the plasmatic concentration of ibuprofen after its oral administration in low to high doses [20].…”

Section: Results and Discussion Hplc Analysismentioning

confidence: 99%

Research Article. The Influence of Some Parameters on Chiral Separation of Ibuprofen by High-Performance Liquid Chromatography and Capillary Electrophoresis

Balint

Cârje

Muntean

et al. 2017

Acta Medica Marisiensis

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Objective: The aim of the study was to compare the influence of mobile phase composition and temperature on chiral separation of racemic ibuprofen by capillary electrophoresis and high performance liquid chromatography with UV detection. Materials and methods: Racemic ibuprofen was analysed on a chiral OVM column with an HPLC system 1100 Agilent Technologies, under isocratic elution, by using potassium dihydrogen phosphate 20 mM and ethanol in mobile phase. The flow rate was set at 1 mL/min, UV detector at 220 nm and different column temperatures were tested. For electrophoresis separation an Agilent CE G1600AX Capillary Electrophoresis System system, with UV detection, was used. The electrophoresis analysis was performed at different pH values and temperatures, with phosphate buffer 25 mM and methyl-β-cyclodextrin as chiral selector. Results: The chromatograhic analysis reveals a high influence of mobile phase pH on ibuprofen enantiomers separation. An elution with a mixture of potassium dihydrogen phosphate 20 mM pH=3 and ethanol, at 25ºC, allowed enantiomers separation with good resolution in less than 8 min. Conclusions: The proposed HPLC method proved suitable for the separation of ibuprofen enantiomers with a good resolution, but the capillary electrophoresis tested parameters did not allow chiral discrimination.

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“…Another approach is to alter the drug formulation in order to enhance dispersion and dissolution to shorten the time to achieving therapeutic plasma concentrations, which for ibuprofen may be in the region of 5–10 μg/ml . T max is traditionally used as a surrogate marker for determining relative onset of action.…”

Section: Discussionmentioning

confidence: 99%

“…[21,22] Another approach is to alter the drug formulation in order to enhance dispersion and dissolution to shorten the time to achieving therapeutic plasma concentrations, which for ibuprofen may be in the region of 5-10 lg/ml. [23] T max is traditionally used as a surrogate marker for determining relative onset of action. The time/concentration absorption curve, when shifted to the left, is usually associated with an earlier onset of analgesic action and improved efficacy.…”

Section: Discussionmentioning

confidence: 99%