The Clinical Pharmacology of Anastrozole

European Oncology & Haematology, 2011;7(2):106-108

Abstract:

Anastrozole is a potent non-steroidal aromatase inhibitor that selectively inhibits aromatase. It is the first aromatase inhibitor approved by the US Food and Drug Administration as an adjuvant hormonal therapy in early-stage breast cancer. With most patients needing to take anastrozole for two to five years, it is important for physicians to understand the clinical pharmacology of anastrozole. Anastrozole has excellent oral bioavailability and is widely distributed throughout the body. It is extensively metabolised by the liver, with a half-life of 40–50 hours. Anastrozole is primarily excreted through the faecal route. Steady-state concentrations are achieved after seven days of once-daily administration. The standard dosage of anastrozole is 1mg/day orally. No dose adjustments are necessary based on hepatic or renal dysfunction. No significant drug–drug interaction has been reported with anastrozole use. This article is to summarise the existing knowledge of the pharmacokinetics of anastrozole.
Keywords: Anastrozole, pharmacokinetics, aromatase inhibitor, breast carcinoma, oestrogen, post-menopausal
Disclosure: The authors have no conflicts of interest to declare.
Received: March 15, 2010 Accepted September 10, 2010 Citation European Oncology & Haematology, 2011;7(2):106-108
Correspondence: Ting Bao, 22 S Greene Street, Baltimore, MD 21201, US. E: tbao@umm.edu

Breast cancer is the most common cancer and the second most common cause of cancer death among women in the US.1 It is estimated that two-thirds of the invasive breast cancers will be hormone-receptor-positive and will require long-term adjuvant hormonal therapy.

Reducing the effect of oestrogen is the main aim of hormonal therapy in treating hormone-receptor-positive breast cancer. The effect of oestrogen is reduced in two ways – by blocking the oestrogen receptor or by inhibiting oestrogen biosynthesis. The mechanism of action of aromatase inhibitors (AIs) is to inhibit oestrogen biosynthesis. AIs have established their role in treating metastatic hormone-receptor-positive breast cancer in post-menopausal women through a number of clinical trials.2–5 In addition, multiple clinical trials have shown that AIs have superior efficacy compared with tamoxifen as an adjuvant hormonal therapy in post-menopausal women with hormone-receptor-positive breast cancer.6–11 AIs are therefore the recommended first-line adjuvant hormonal therapy in post-menopausal women with hormone-receptor-positive breast cancer, either as monotherapy or as sequential therapy after tamoxifen.

The recommended duration of adjuvant AI therapy is usually two to five years. With the recommended treatment period being up to five years in the adjuvant setting, it is important for physicians to understand the clinical pharmacology of some of the commonly used AIs.

Aromatase Inhibitor Development
AIs have been around for over 20 years. Aminoglutethimide was the first AI in general clinical use. Its use was limited by its intermediate efficacy in inhibiting aromatisation and its low specificity, which resulted in significant side effects.12,13 Roglethimide was the second glutethimide derivative, whose use was limited by its low potency and significant side effects.14,15 The second-generation AI fadrozole was then developed and was found to be more specific than aminoglutethimide. It still has significant side effects as it suppresses aldosterone synthesis.16,17 The third-generation AIs anastrozole, letrozole and exemestane have been developed most recently. They are superior in both their high oestrogen biosynthesis suppression and their specificity, resulting in very few side effects.18 Among them, anastrozole and letrozole are non-steroidal AIs, whereas exemestane is steroidal. Anastrozole was the first third-generation AI to be tested in clinical trials in treating metastatic and early-stage hormonereceptor- positive breast cancer in post-menopausal women.
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Keywords: Anastrozole, pharmacokinetics, aromatase inhibitor, breast carcinoma, oestrogen, post-menopausal