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.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006400:Hematocrit; D007016:Hypophysectomy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000097:blood / Q000494:pharmacology*; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*
D001798:Blood Proteins; D002110:Caffeine; D013806:Theophylline; D013805:Theobromine; D003345:Corticosterone