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Pharmacotherapeutic group: Steroidal aromatase inhibitor; anti-neoplastic agent.
Pharmacology: Pharmacodynamics: 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 postmenopausal women. In postmenopausal women, orally administered Exemestane significantly lowered serum oestrogen concentrations starting from a 5 mg dose, reaching maximal suppression (>90%) with a dose of 10-25 mg. In postmenopausal breast cancer patients treated with the 25 mg daily dose, whole body aromatization was reduced by 98%.
Exemestane does not possess any progestogenic or oestrogenic activity. A slight androgenic activity, probably due to the 17-hydro derivative, has been observed mainly at high doses. In multiple daily doses trials, Exemestane had no detectable effects on adrenal biosynthesis of cortisol or aldosterone, measured before or after ACTH challenge, thus demonstrating its selectivity with regard to the other enzymes involved in the steroidogenic pathway. These findings indicate that glucocorticoid or mineralcorticoid replacements are not warranted.
A slight non-dose-dependent increase in serum LH and FSH levels has been observed even at low doses. However, this pharmacological class effect is expected and probably results from feedback at the pituitary level due to the reduction in estrogen levels that stimulate the pituitary secretion of gonadotropins (also in post-menopausal women).
Pharmacokinetics: This study was designed as a randomized open label, balanced, two treatment, two period, two sequence, single dose, crossover, bioequivalence study of Exemestane 25 mg tablets in normal, adult, healthy, post menopausal/surgically sterile female subjects under fed conditions. The study was conducted following an oral administration of one tablet 25 mg of the test drug or one tablet 25 mg of the reference drug.
Based on statistical analysis of the 90% Confidence Interval (Log-transformed data) of Test Drug and Reference Drug for AUC0-inf, AUC0-t, and Cmax were 95.70 - 102.48, 95.77 - 102.61 and 91.76 - 107.22, respectively.
Geometric mean of Test Drug and Reference Drug were 58500.41 and 59071.31 for AUC0-inf; 56946.55 and 57448.18 for AUC0-t; 18612.17 and 18764.05 for Cmax.
Conclusion: Based on the statistical analysis results, Exemestane 25 mg tablets is bioequivelent with the reference drug.
