Adverse effects of dexamethasone used as CYP3A inducer in rats

Dexamethasone, and some other glucocorticoids, are known to be inducers of cytochrome P-450 3A isoform (CYP3A). However, little information is found i n the literature about the adverse effects related to such inducing treatme nt, especially on the important body weight loss which makes treated animal s more vulnerable to subsequent treatment with other drugs. In view to obtain adequate CYP3A induction in male and female rats while mi nimizing body weight loss and mortality after further in vivo treatment wit h other drugs, we successively varied cumulated dosage (300 to 600 mg/kg), concentration (100 to 150 mg/kg/day), duration of DEX administration (3 or 4 days), and delay before sacrifice after last DEX administration (24 to 72 h), and determined CYP3A activity by western blot. Results show that a single daily p.o. administration of 100 mg/kg DEX durin g 3 days (cumulated dosage = 300 mg/kg), with sacrifice 24 h after last DEX administration, produces an acceptable CYP3A induction (vs undetectable am ounts in controls) with a minimum body weight loss.