Pharmacokinetics, pharmacodynamics and safety profiling of IS01957, a preclinical candidate possessing dual activity against inflammation and nociception

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

“…Results of P eff for diclofenac as alone, IS01957 as alone, diclofenac upon prior oral treatment with IS01957 are illustrated in Figure . IS01957 was found to have high permeability which is consistent with the previously reported results using PAMPA model (Sharma, Magotra, Dogra, et al, ). P eff of diclofenac was enhanced by prior oral treatment of IS01957 (7.8 × 10 −5 cm/s) in comparison to diclofenac alone group (2.8 × 10 −5 cm/s).…”

“…Results showed that combination of diclofenac (10 mg/kg) with IS01957 (10 mg/kg) inhibited the carrageenan induced paw edema significantly greater than the individual diclofenac or IS01957 at same dose level (Figure ). IS01957 also have pronounced effect in the different animal model of inflammation and nociception as described earlier (Sharma, Magotra, Dogra, et al, ). At this point, it was imperitive to understand the cause for these augmented efficacy which might be due to its individual potential or any pharmacokinetic changes of diclofenac.…”

“…IS01957, chemically [(E)‐3‐(4‐butoxyphenyl)‐1‐morpholinoprop‐2‐ene‐1‐one)] (Figure ) derived from para‐coumaric acid was found to have dual action against inflammation and nociception with acceptable safety pharmacological profile (Sharma, Magotra, Dogra, et al, ; Sharma, Magotra, Rath, et al, ). It has been developed in our institute under the purview of anti‐inflammatory drug and bioenhancer (Taneja, Koul, Koul, Moza, & Handa, ).…”

“…From the above discussion, it is clear that the use of bioenhancer is a systematic approach for the intended pharmacokinetic interaction of the drug with another molecule to increase the plasma level of the particular drug that can be beneficial for its dose reduction and subsequent toxicity. IS01957, chemically [(E)-3-(4-butoxyphenyl)-1-morpholinoprop-2-ene-1-one)] (Figure 1) derived from para-coumaric acid was found to have dual action against inflammation and nociception with acceptable safety pharmacological profile (Sharma, Magotra, Dogra, et al, 2017;. It has been developed in our institute under the purview of anti-inflammatory drug and bioenhancer (Taneja, Koul, Koul, Moza, & Handa, 2006).…”

Intervention of curcumin on oral pharmacokinetics of daclatasvir in rat: A possible risk for long‐term use

“…Different study groups are represented in Table . Each study was done by using 15 animals, divided into three subgroups ( n = 5) for sparse sampling (Magotra et al, ; Sharma et al, ), that is, three blood samples (120 μl each) from every subgroups at different time points were collected from retro‐orbital plexus. Animals were fasted for 10 hr prior to experimentation with free access to water.…”