hepatic glycogen depletion in fed female rats induced by piroxicam the effects of ip piroxicam administration on hepatic glycogen levels and enzymatic activities of key enzymes involved into glycogen metabolism in fed female rats were studied liver glycogen concentrations in treated rats decreased with increasing time of treatment and doses of piroxicam administered the fall in glycogen caused by piroxicam persisted for several days after it was discontinued neither nadolol nor phenobarbital administration were able to prevent the depleting effect of piroxicam in the treated rats glucose6phosphatase glycogen phosphorylase and glycogen synthase activities remained unchanged respect to control also proportion of phosphorylase in the active a form was not significantly affected by successive piroxicam daily doses in contrast we demonstrated a decrease in the glycogen synthase in the active i form this reduction was timedependent on piroxicam treatment further glucose loads were not capable to restore activity in the synthase enzyme and liver glycogen synthesis in animals treated with piroxicam the impairment into glycogen metabolism produced by piroxicam administration suggests liver becomes unable to maintain glucose homeostasis furthermore glycogen depletion might produce an impairment in the metabolism of drugs administered simultaneously with piroxicam because biotransformation of xenobiotics is a process depending on glycogen storage in the liver cells