Pharmacokinetics (PK) of Aromasin® (exemestane, EXE) after single and repeated doses in healthy postmenopausal volunteers (HPV)

Spinelli, R.; Jannuzzo, M. G.; Poggesi, Italo; Frevola, L.; Broutin, F.; Cicioni, P.; Marrari, P.; Coz, F. Le

doi:10.1016/s0959-8049(99)81605-0

Cited by 20 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The maximum plasma concentration, time to achieve maximal concentrations and oral clearance for exemestane after oral administration of a single dose of 25 mg in the present study of males were similar to those reported for females (21)(22)(23). The terminal half-life in the present study (8.9 h) was considerably shorter than the published value of 27 h (23).…”

Section: Discussionsupporting

confidence: 87%

Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

Mauras

Lima

Patel

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Suppression of estrogen, via estrogen receptor or aromatase blockade, is being investigated in the treatment of different conditions. Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor. To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14 -26 yr of age) were recruited. In a cross-over study, 12 were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a 14-d washout period. Blood was withdrawn before and 24 h after the last dose of each treatment period. A PK study was performed (n ‫؍‬ 10) using a 25-mg dose. Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P < 0.002); 50 mg, 32% (P < 0.008)], with a reciprocal increase in testosterone concentrations (60% and 56%; P < 0.003 for both). Plasma lipids and IGF-I concentrations were unaffected by treatment. The PK properties of the 25-mg dose showed the highest exemestane concentrations 1 h after administration, indicating rapid absorption. The terminal half-life was 8.9 h. Maximal estradiol suppression of 62 ؎ 14% was observed at 12 h. The drug was well tolerated. In conclusion, exemestane is a potent aromatase inhibitor in men and an alternative to the choice of available inhibitors. Long-term efficacy and safety will need further study. (J Clin Endocrinol Metab 88: 5951-5956, 2003)

show abstract

Section: Discussionsupporting

confidence: 87%

Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

Mauras

Lima

Patel

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…In separate single-agent studies, these nonsteroidal AIs have been shown to be metabolized differently than is the steroidal AI, exemestane, for example. Anastrozole is metabolized by N-dealkylation, hydroxylation and glucuronidation and letrozole, by the isoenzymes, cytochrome P-450 3A4 and 2A6, whereas exemestane is broken down by cytochrome P-450 34A and by aldoketoreductases (7,19,20).…”

Section: Discussionmentioning

confidence: 99%

Pilot Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of the Combination of Exemestane and Tamoxifen

Rivera

Valero

Francis

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer.Experimental Design: Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after ϳ4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting.Results: We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after ϳ4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5-19 months).Conclusions: This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.

show abstract

“…These results suggest a nonlinear relation between the dose and the efficacy of letrozole. The half‐lives of anastrozole (1 mg) and exemestane (25 mg) are 41 hours32 and 27 hours,33 respectively, whereas it has been reported that the half‐life for letrozole (2.5 mg) is up to 4 days 34, 35…”

Section: Comparative Clinical Pharmacologymentioning

confidence: 99%

An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Buzdar¹,

Robertson²,

Eiermann³

et al. 2002

Cancer

283

182

View full text Add to dashboard Cite

BACKGROUND The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first‐line treatments and compared with megestrol acetate as second‐line therapy in postmenopausal women with advanced breast carcinoma. In an open‐label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles. METHODS In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane. RESULTS At clinically administered doses, the plasma half‐lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41–48 hours, 2–4 days, and 27 hours, respectively. The time to steady‐state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis. CONCLUSIONS All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long‐term clinical significance of these differences remains to be elucidated. Cancer 2002;95:2006–16. © 2002 American Cancer Society. DOI 10.1002/cncr.10908

show abstract

Pharmacokinetics (PK) of Aromasin® (exemestane, EXE) after single and repeated doses in healthy postmenopausal volunteers (HPV)

Cited by 20 publications

References 0 publications

Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

Pilot Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of the Combination of Exemestane and Tamoxifen

An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Contact Info

Product

Resources

About