Pharmacokinetics

Anastrozole is administered orally. Pharmacokinetics are linear, even with repeated dosing. Hepatic metabolism accounts for approximately 85% of elimination. Within 72 hours, about 60% of a dose is excreted in the urine as metabolites and only 10% as unchanged drug. Three metabolites have been identified in plasma and urine, and there are several unidentified minor metabolites. No pharmacological activity has been attributed to triazole, the main circulating metabolite. The other known metabolites are a glucuronide conjugate of hydroxy-anastrozole and a glucuronide conjugate of anastrozole. Anastrozole has a terminal elimination half-life of about 50 hours.

Per the manufacturer, it is unlikely that anastrozole administered at the recommended dose will inhibit the metabolism of cytochrome P450-mediated drugs given concomitantly. High concentrations inhibited metabolic reactions catalyzed by cytochromes P450 (CYP) 1A2, 2C8/9, and 3A4. It did not inhibit CYP2A6 or the polymorphic CYP2D6 in human liver microsomes.(9)

Route-Specific Pharmacokinetics:

Oral Route: Anastrozole is well absorbed and distributed throughout the systemic circulation (85% bioavailability). Maximum plasma concentrations occur within 2 hours.(7) Plasma concentrations approach steady-state levels by about the seventh day of once-daily dosing.

Special Populations:

Hepatic Impairment: Although hepatic cirrhosis reduces apparent oral clearance of anastrozole, no dosage adjustments are needed because plasma concentrations remain within the same range as for patients without hepatic disease.

Renal Impairment: Renal clearance of anastrozole does decrease proportionally with creatinine clearance, but overall this has very little effect on total body clearance. No dosage adjustments are therefore necessary for patients with impaired renal function.