Studies on methyl-xanthines in intact and hypophysectomised rats: differences in pharmacokinetics and adrenocortical response.

The effects of caffeine (Cf), theophylline (Tph) and theobromine (Tb) on the adrenal cortex were studied. No direct effect (hypophysectomized: hypo(-) rats) was observed with any of the three methyl-xanthines (MX) after chronic oral administration (5 days). An indirect effect (via the hypothalamo-hypophyseal-adrenal axis) was found for theophylline: plasma and adrenal corticosterone levels were increased in intact rats, after acute or chronic treatment. The high toxicity of MX (mainly Tph) observed in hypo(-) rats prompted the study of pharmacokinetic parameters: the clearance was decreased and the half-life was increased by a factor 3 for Cf and 1.6 for Tph. Thus, the elimination of Cf and Tph was slowed down in hypo(-) rats.