Nateran Mechanism of Action

Pharmacology: Mechanism of action: Exemestane is an irreversible, steroidal aromatase inhibitor, structurally related to the natural substrate androstenedione. In post-menopausal women, oestrogens are produced primarily from the conversion of androgens into oestrogens through the aromatase enzyme in peripheral tissues. Oestrogen deprivation through aromatase inhibition is an effective and selective treatment for hormone dependent breast cancer in post-menopausal women. In post-menopausal women, Exemestane p.o. significantly lowered serum oestrogen concentrations starting from a 5 mg dose, reaching maximal suppression (>90%) with a dose of 10-25 mg. In post-menopausal breast cancer patients treated with the 25 mg daily dose, whole body aromatization was reduced by 98%.
Pharmacokinetics: The pharmacokinetics parameters of 56 subjects (54 subjects completed all 4 study periods and 2 subjects completed 2 study periods) were calculated and results were statistically analyzed for average bioequivalence in 2-treatment 4-period 2-sequence replicate crossover design.
After oral administration of Exemestane 25 mg film-coated tablets (test product) the mean of the maximum plasma concentration (C_max) (rate of absorption) was 24.70 ng/ml and this C_max was reached at the mean T_max of 1.55 h. The extent of absorption is expressed in Area Under the curve (AUC)_0-t and AUC_0-inf. The mean values were 54.88 ng.h/ml and 59.08 ng.h/ml respectively. The mean elimination half-life (t_½) of exemestane 25 mg film-coated tablets was 8.01 h.
The ratios and confidence intervals between test and reference product were as follows: For C_max the ratio was 100.42% (94.12%-107.17%). For AUC_0-t the ratio was 103.72% (100.81-106.72%). For AUC_0-inf, the ratio was 103.49% (100.62%-106.44%). The results of the study showed that the ratios are within the acceptance range for bioequivalence, therefore it can be concluded that the test product, Exemestane 25 mg film-coated tablets, is bioequivalent with the reference product.