[Glucocorticoid action of beclomethasone and its propionate ester derivatives].
In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone.
[Glucocorticoid action of beclomethasone and its propionate ester derivatives]. In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone.