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The following is a summary of “Comparative Evaluation of Cyclooxygenase Inhibition Profiles Across Various NSAID Forms and Doses: Implications for Efficacy and Adverse Effects,” published in the December 2024 issue of Pain by Shirakawa et al.
Despite extensive research on COX inhibition by Nonsteroidal anti-inflammatory drugs (NSAIDs), studies comparing the inhibitory concentrations to clinical plasma levels and assessing efficacy and adverse effects across different dosage forms lacked.
Researchers conducted a retrospective study to assess the COX inhibitory activities and inhibition rates of clinical doses of various NSAID formulations, particularly diclofenac sodium.
They mixed human blood with diclofenac sodium, celecoxib, ibuprofen, flurbiprofen, or etodolac, incubated the mixture, and collected the supernatant to quantify COX inhibitory activity using ELISA. Logistic regression analyses were performed to estimate the inhibition rates at maximum plasma drug concentration (Cmax) for clinical doses of marketed formulations. For diclofenac sodium, the concentrations at which COX inhibition rates were 80% and 50% (IC80 and IC50) were also determined.
The results showed that the COX-2 inhibition rate at the Cmax of clinical doses exceeded 50%, except for celecoxib, which was 100 mg. For diclofenac sodium, the Cmax at clinical doses of both oral and suppository formulations resulted in almost complete COX-2 inhibition and an inhibition rate surpassing IC80 for COX-1. The Cmax at frequent doses of the transdermal formulation achieved COX-2 inhibition above IC80, but COX-1 inhibition remained below IC80.
Investigators concluded the transdermal formulation exhibited an analgesic effect despite lower Cmax compared to other diclofenac sodium formulations.
Source: link.springer.com/article/10.1007/s40122-024-00687-2
