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Significant improvements were reported in fasting blood glucose, HbA1c and HOMA index in diabetic patients for both doses. The most common side effects, in order of frequency, were: dry mouth, paresthesias, constipation, upper respiratory tract infection, taste alteration and insomnia. The control of energy homeostasis and body weight involves complex interactions between the CNS and peripheral neurohormonal signals from the adipose tissue, pancreas and GI tract.
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Selective COX-2 inhibition was also observed in ex vivo blood samples from healthy human volunteers who received etoricoxib at various therapeutic and supratherapeutic doses Dallob et al Etoricoxib produced markedly less interference with the cardioprotective COXmediated antiplatelet activity of low-dose aspirin in vitro than other NSAIDs including in ascending order of aspirin antagonism rofecoxib, valdecoxib, celecoxib, and ibuprofen, reflecting the lower affinity of etoricoxib for COX-1 Ouellet et al These findings are consistent with results from clinical studies in which ibuprofen, but not rofecoxib Catella-Lawson et al or etoricoxib Wagner et al, antagonized aspirin antiplatelet activity.
Preclinical and clinical data were consistent with the gastrointestinal tolerability of selective COX-2 inhibition; no effects on gastrointestinal integrity were observed in animal models as measured by urinary or fecal excretion of 51 creatinineethylenediamine tetraacetic acid 51 Cr-EDTA, an inert compound that is not taken up by extravascular tissue after its absorption from the gastrointestinal tract, but is completely excreted by the kidney Riendeau et al Inhibition of prostaglandin synthesis in the gastric mucosa was not significantly different from that of placebo in human volunteers Dallob et al In healthy volunteers, oral etoricoxib is rapidly and completely absorbed.
In contrast, agents that strongly induce CYP3A may reduce etoricoxib concentrations below therapeutic levels Agrawal et al b.
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